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Sample records for arachidonic acid release

  1. Proteasome inhibitors: Their effects on arachidonic acid release from cells in culture and arachidonic acid metabolism in rat liver cells

    OpenAIRE

    Levine Lawrence

    2004-01-01

    Abstract Background I have postulated that arachidonic acid release from rat liver cells is associated with cancer chemoprevention. Since it has been reported that inhibition of proteasome activities may prevent cancer, the effects of proteasome inhibitors on arachidonic acid release from cells and on prostaglandin I2 production in rat liver cells were studied. Results The proteasome inhibitors, epoxomicin, lactacystin and carbobenzoxy-leucyl-leucyl-leucinal, stimulate the release of arachido...

  2. 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 relea...se and cytosolic phospholipase A2activation. Authors Gij

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

    International Nuclear Information System (INIS)

    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

  4. Effect of progesterone on the release of arachidonic acid from human endometrial cells stimulated by histamine

    International Nuclear Information System (INIS)

    Progesterone at concentrations of 10(-7)M and 10(-8)M inhibits release of [3H]-arachidonic acid from stimulated, perfused, endometrial cells. The effect is independent of the mechanism of stimulation. Cortisol (10(-5)M but not 10(-7)M) has a similar effect in this system but estradiol (10(-7)M) is without effect. There was a positive correlation (p less than 0.05) between the magnitude of inhibition by progesterone and the day of cycle. The inhibitory action of progesterone on the release of arachidonic acid was greater in endometrial cells than in decidual cells and was apparent after fifteen minutes. The activities of commercial and endometrial cell-free preparations of phospholipase A2 and phospholipase C were unaffected by the presence of progesterone. We conclude that progesterone modulates release of [3H]-arachidonic acid from endometrial cells by a rapid, indirect action on phospholipase activity

  5. 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...

  6. Photoreactivation of ultraviolet radiation-induced release of arachidonic acid from marsupial cells

    International Nuclear Information System (INIS)

    Exposure of an established marsupial cell line, PtK2 (Potorous tridactylus), to ultraviolet radiation (UVR) from an FS-40 sunlamp (280-400 nm) resulted in a fluence-dependent release of radiolabeled arachidonic acid (AA) from cell membrane. Post-UVR, but not pre-UVR, exposure to photoreactivating light reversed UVR-induced pyrimidine dimers in DNA and suppressed the UVR-induced release of AA. These data indicate that DNA damage contributes to the release of AA from membrane phospholipids. (author)

  7. Photoreactivation of ultraviolet radiation-induced release of arachidonic acid from marsupial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kaleta, E.W.; Applegate, L.A.; Ley, R.D. (Lovelace Foundation for Medical Education and Research, Albuquerque, NM (United States))

    1991-11-01

    Exposure of an established marsupial cell line, PtK{sub 2} (Potorous tridactylus), to ultraviolet radiation (UVR) from an FS-40 sunlamp (280-400 nm) resulted in a fluence-dependent release of radiolabeled arachidonic acid (AA) from cell membrane. Post-UVR, but not pre-UVR, exposure to photoreactivating light reversed UVR-induced pyrimidine dimers in DNA and suppressed the UVR-induced release of AA. These data indicate that DNA damage contributes to the release of AA from membrane phospholipids. (author).

  8. Tamoxifen stimulates arachidonic acid release from rat liver cells by an estrogen receptor-independent, non-genomic mechanism

    International Nuclear Information System (INIS)

    Tamoxifen is widely prescribed for the treatment of breast cancer. Its success has been attributed to the modulation of the estrogen receptor. I have previously proposed that the release of arachidonic acid from cells may also mediate cancer prevention. Rat liver cells were radiolabelled with arachidonic acid. The release of [3H] arachidonic acid after various times of incubation of the cells with tamoxifen was measured. Tamoxifen, at micromolar concentrations, stimulates arachidonic acid release. The stimulation is rapid and is not affected by pre-incubation of the cells with actinomycin or the estrogen antagonist ICI-182,780. The stimulation of AA release by tamoxifen is not mediated by estrogen receptor occupancy and is non-genomic

  9. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release

    OpenAIRE

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G.

    2005-01-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) which couple Gαi and Gαq proteins to release arachidonic acid (AA) and elevate [Ca2+]i. Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Gαi, Gαq and Gα12/13 proteins. In CHO cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human e...

  10. Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung.

    OpenAIRE

    Bakhle, Y. S.; Moncada, S.; de Nucci, G.; Salmon, J A

    1985-01-01

    The effects of infusions of bradykinin (0.2 microM), calcium ionophore A23187 (0.5 microM) and arachidonic acid (13 microM) on the release of eicosanoids from the guinea-pig isolated perfused lung were investigated using radioimmunoassay for thromboxane B2 (TXB2), 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), PGE2, leukotriene B4 (LTB4) and LTC4 and bioassay using the superfusion cascade. Bradykinin released more 6-oxo-PGF1 alpha than TXB2, whereas arachidonic acid and ionophore released m...

  11. 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)

    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 (14C)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 A2 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

  12. Measurement of arachidonic acid release from human polymorphonuclear neutrophils and platelets: comparison between gas chromatographic and radiometric assays

    International Nuclear Information System (INIS)

    a simple gas chromatographic method for the assay of phospholipase A2 (PLA2) has been described in which arachidonic acid released from endogenous phospholipid pools is measured following its extraction and derivatization to pentafluorobenzyl esters. Using this assay, PLA2 activities in control and calcium ionophore-stimulated human neutrophils, as well as in control, thrombin, and calcium ionophore stimulated human platelets, have been measured. These values are compared with those obtained by monitoring the release of radioactivity from 3H- or 14Carachidonic acid prelabeled cells. While the radiometric assay measures only the release of exogenously incorporated radioactive arachidonic acid, the gas chromatographic assay measures arachidonic acid released from all the endogenous pools. Thus, the apparent increase in PLA2 activity in stimulated cells measured by the gas chromatographic assay is four- to fivefold higher than that by the radiometric assay. Inclusion of fatty acid free bovine serum albumin in the reaction buffer significantly increases the amount of arachidonic acid that is measured by gas chromatography. The gas chromatographic method has also been successfully utilized for measuring PLA2 activity in cell-free preparations derived from physically disrupted human neutrophils

  13. Release of arachidonic acid from oligodendrocytes by terminal complement proteins, C5b-C9

    International Nuclear Information System (INIS)

    Activation of C5b-C9 on monocytes, macrophages, platelets and neutrophils induces membrane lipid hydrolysis and generates arachidonic acid (AA) and its oxygenated derivatives. Additionally, activation of C5b-C9 and myelin lipid hydrolysis has been observed in demyelination. The authors have investigated the modulatory effect of C5b-9 on membrane lipid hydrolysis of oligodendrocytes (OLG), the myelin producing cells in the central nervous system. Antibody-sensitized rat OLG, prelabeled with 14C AA were treated with excess C6-deficient rabbit serum reconstituted with limiting doses of C6. Qualitative analysis of the supernatants by HPLC revealed the presence of both cyclooxygenase and lipooxygenase products. Prostaglandin E2, leukotriene (LT) E4, LTB4 and free AA were the major radiolabeled products. The kinetics and dose response of LTB4 release with respect to the cytolytic dose of C5b-9 were quantitated by radioimmunoassay. LTB4 release approached maximum in 1 hr and higher amounts were detected with fewer C5b-9 channels. Addition of C8 to OLG bearing C5b-7 intermediates induced maximum LTB4 release without further enhancement by C9 in contrast to the absolute requirement of C9 in mediator release from rat neutrophils. Thus, the requirement of C5b-8 or C5b-9 in mediator release appears to be cell-type dependent

  14. 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

    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...

  15. Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [C]arachidonic acid and histamine from rat peritoneal mast cells

    DEFF Research Database (Denmark)

    Jacobsen, S.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    Thapsigargin is a potent skin irritating sesquiterpene lactone isolated from the roots of Thapsia garganica L. (Apiaceae). In rat peritoneal mast cells thapsigargin induced a calcium-dependent non-cytotoxic [C]arachidonic acid and histamine release. A minor amount of the released [C]arachidonic a...

  16. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release.

    Science.gov (United States)

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G

    2006-03-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) that couple Galpha(i) and Galpha(q) proteins to release arachidonic acid (AA) and elevate intracellular Ca2+ concentration ([Ca2+]i). Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Galpha(i), Galpha(q), and Galpha(12/13) proteins. In Chinese hamster ovary cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human endothelial cells expressing both Rs constitutively. The PAR1 agonist hexapeptide (TRAP) was as effective as thrombin. Inhibitors of components of Galpha(i), Galpha(q), and Galpha(12/13) signaling pathways, and a protein kinase C (PKC)-alpha inhibitor, Gö-6976, blocked potentiation, while phorbol, an activator, enhanced it. Several inhibitors, including a RhoA kinase inhibitor, a [Ca2+]i antagonist, and an inositol-(1,3,4)-trisphosphate R antagonist, reduced mobilization of [Ca2+]i by thrombin and blocked potentiation of AA release by B2R agonists. Because either a nonselective inhibitor (isotetrandrine) of phospholipase A2 (PLA2) or a Ca2+-dependent PLA2 inhibitor abolished potentiation of AA release by thrombin, while a Ca2+-independent PLA2 inhibitor did not, we concluded that the mechanism involves Ca2+-dependent PLA2 activation. Both thrombin and TRAP modified activation and phosphorylation of the B2R induced by BK. In lower concentrations they enhanced it, while higher concentrations inhibited phosphorylation and diminished B2R activation. Protection of the NH2-terminal Ser1-Phe2 bond of TRAP by an aminopeptidase inhibitor made this peptide much more active than the unprotected agonist. Thus PAR1 activation enhances AA release by B2R agonists through signal transduction pathway. PMID:16183725

  17. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release

    Science.gov (United States)

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G.

    2006-01-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) which couple Gαi and Gαq proteins to release arachidonic acid (AA) and elevate [Ca2+]i. Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Gαi, Gαq and Gα12/13 proteins. In CHO cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human endothelial cells expressing both Rs constitutively. The PAR1 agonist hexapeptide (TRAP) was as effective as thrombin. Inhibitors of components of Gαi, Gαq and Gα12/13 signaling pathways, and a PKCα inhibitor, Gö6976 blocked potentiation while phorbol, an activator, enhanced it. Several inhibitors, including a RhoA kinase inhibitor, a [Ca2+]i antagonist, and an inositol-(1,3,4)-trisphosphate R antagonist, reduced mobilization of [Ca2+]i by thrombin and blocked potentiation of AA release by B2R agonists. Because either a non-selective inhibitor (isotetrandrine) of phospholipase A2 (PLA2) or a Ca2+-dependent PLA2 inhibitor abolished potentiation of AA release by thrombin, while a Ca2+-independent PLA2 inhibitor did not, we concluded that the mechanism involves Ca2+-dependent PLA2 activation. Both thrombin and TRAP modified activation and phosphorylation of the B2R induced by BK. In lower concentrations they enhanced it, while higher concentrations inhibited phosphorylation and diminished B2R activation. Protection of the N-terminal Ser1-Phe2 bond of TRAP by an aminopeptidase inhibitor made this peptide much more active than the unprotected agonist. Thus, PAR1 activation enhances AA release by B2R agonists through signal transduction pathway. PMID:16183725

  18. Ca2+-dependent and Ca2+-independent pathways for release of arachidonic acid from phosphatidylinositol in endothelial cells

    International Nuclear Information System (INIS)

    The pathways for degradation of phosphatidylinositol (PI) were investigated in sonicated suspensions prepared from confluent cultures of bovine pulmonary artery endothelial cells. The time courses of formation of 3H-labeled and 14C-labeled metabolites of phosphatidyl-[3H]inositol ([3H]Ins-PI) and 1-stearoyl-2-[14C] arachidonoyl-PI were determined at 370C and pH 7.5 in the presence of 2 mM EDTA with or without a 2 mM excess of Ca2+. The rates of formation of lysophosphatidyl-[3H]inositol ([3H]Ins-lyso-PI) and 1-lyso-2-[14C] arachidonoyl-PI were similar in the presence and absence of Ca2+, and the absolute amounts of the two radiolabeled lyso-PI products formed were nearly identical. This indicated that lyso-PI was formed by phospholipase A1, and phospholipase A2 was not measurable. In the presence of EDTA, [14C]arachidonic acid release from 1-stearoyl-2-[14C]arachidonoyl-PI paralleled release of glycerophospho-[3H]inositol ([3H]GPI) from [3H]Ins-PI. Formation of [3H]GPI was inhibited by treatment with the specific sulfhydryl reagent, 2,2'-dithiodipyridine, and this was accompanied by an increase in [3H]Ins-lyso-PI. In the presence of Ca2+, [14C] arachidonic acid release from 1-stearoyl-2-[14C]arachidonoyl-PI was increased 2-fold and was associated with Ca2+-dependent phospholipase C activity. Under these conditions, [3H]inositol monophosphate production exceeded formation of [14C]arachidonic acid-labeled phospholipase C products, diacylglycerol plus monoacylglycerol, by an amount that was equal to the amount of [14C]arachidonic acid formed in excess of [3H]GPI. Low concentrations of phenylmethanesulfonyl fluoride (15-125 microM) inhibited Ca2+-dependent [14C]arachidonic acid release, and the decrease in [14C] arachidonic acid formed was matched by an equivalent increase in 14C label in diacylglycerol plus monoacyclglycerol

  19. In vitro ozone exposure increases release of arachidonic acid products from a human bronchial epithelial cell line

    Energy Technology Data Exchange (ETDEWEB)

    McKinnon, K.P.; Madden, M.C.; Noah, T.L.; Devlin, R.B. (TRC Environmental Corporation, Chapel Hill, NC (United States))

    1993-02-01

    Eicosanoids released after ozone exposure of a human bronchial epithelial cell line, BEAS-S6, were analyzed by high-pressure liquid chromatography (HPLC) of supernatants from exposed cells prelabeled with [3H]arachidonic acid. BEAS cells released thromboxane B2 (TxB2), prostaglandin E2 (PGE2), leukotriene C4 (LTC4), LTD4, LTE4, and 12-hydroxyheptadecatrienoic acid (HHT) after exposure to ozone at concentrations of 0.1, 0.25, 0.5, and 1.0 ppm. The eicosanoids were identified by coelution with authentic standards. The largest product from ozone-exposed BEAS cells was the most polar peak, designated Peak 1. Release of cyclooxygenase products such as TxB2, PGE2, and HHT was inhibited by acetylsalicylic acid. Peaks that migrated with authentic standards for LTB4, LTC4, and LTD4 were inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid. The leukotrienes LTB4 and LTC4/D4 could also be detected by immunoassay of concentrated peak fractions. Thus BEAS cells released eicosanoids from cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism following exposure to ozone. Airway epithelial cells may be an important source of eicosanoids following ozone stimulation in humans.

  20. In vitro release of arachidonic acid metabolites, glutathione peroxidase, and oxygen-free radicals from platelets of asthmatic patients with and without aspirin intolerance.

    OpenAIRE

    Plaza, V.; J. Prat; Rosellò, J.; Ballester, E; Ramis, I; Mullol, J; Gelpí, E; Vives-Corrons, J. L.; Picado, C.

    1995-01-01

    BACKGROUND--An abnormal platelet release of oxygen-free radicals has been described in acetylsalicylic acid (aspirin)-induced asthma, a finding which might suggest the existence of an intrinsic, specific platelet abnormality of arachidonic acid metabolism in these patients. The objective of this study was to evaluate platelet arachidonic acid metabolism in asthmatic patients with or without intolerance to aspirin. METHODS--Thirty subjects distributed into three groups were studied: group 1, 1...

  1. 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

    Directory of Open Access Journals (Sweden)

    Levine Lawrence

    2004-08-01

    Full Text Available Abstract Background 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. Methods Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [3H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I2 produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. Results 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 I2 production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I2 production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. Conclusions 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.

  2. 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)

    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 [3H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I2 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 I2 production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I2 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

  3. Role of arachidonic acid metabolism on corticotropin-releasing factor (CRF)-release induced by interleukin-1 from superfused rat hypothalami.

    Science.gov (United States)

    Cambronero, J C; Rivas, F J; Borrell, J; Guaza, C

    1992-07-01

    The present work shows that the corticotropin-releasing factor (CRF)-releasing activity of interleukin-1 (IL-1) is partially inhibited by a phospholipase A2 (mepacrine) or a cyclooxygenase (indomethacin) inhibitor, but is not affected by inhibition of the lypoxygenase pathway with norhydroguaiaretic acid. These results indicate that the metabolism of arachidonic acid plays an important role as mediator of the effects of IL-1 on CRF release. It is also shown that products of the cyclooxygenase activity such as prostaglandins can stimulate CRF secretion by a direct action on the hypothalamus. Whereas PGE2 failed to induce increases on CRF release, PGF2 alpha stimulated in a dose-dependent manner (21-340 nM), the CRF release from continuous perifused hypothalami. It is suggested that PGF2 alpha could be involved as a messenger in the hypothalamic CRF secretion induced by IL-1. PMID:1619039

  4. The Property and Application of Arachidonic Acid

    Institute of Scientific and Technical Information of China (English)

    王相勤; 姚建铭; 袁成凌; 王纪; 余增亮

    2002-01-01

    Arachidonic acid (AA) is one of the most important PUFAs (polyunsaturated fatty acids) in human body. A high-yield arachidonic acid-producing strain (mortierella alpina) was selected by ion implantation (the relative content of arachidonic acid is 70.2% among all fatty acids). This paper mainly introduced the structure, distribution, source, physiologic healthcare function and application of AA.

  5. The property and application of arachidonic acid

    International Nuclear Information System (INIS)

    Arachidonic acid (AA) is one of the most important PUFAs (polyunsaturated fatty acids) in human body. A high-yield arachidonic acid-producing strain (mortierella alpina) was selected by ion implantation (the relative content of arachidonic acid is 70.2% among all fatty acids). The author mainly introduced the structure, distribution, source, physiologic health care function and application of AA

  6. Oxygen metabolites stimulate release of high-molecular-weight glycoconjugates by cell and organ cultures of rodent respiratory epithelium via an arachidonic acid-dependent mechanism.

    OpenAIRE

    Adler, K B; Holden-Stauffer, W J; Repine, J E

    1990-01-01

    Several common pulmonary disorders characterized by mucus hypersecretion and airway obstruction may relate to increased levels of inhaled or endogenously generated oxidants (O2 metabolites) in the respiratory tract. We found that O2 metabolites stimulated release of high-molecular-weight glycoconjugates (HMG) by respiratory epithelial cells in vitro through a mechanism involving cyclooxygenase metabolism of arachidonic acid. Noncytolytic concentrations of chemically generated O2 metabolites (...

  7. 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.

  8. Effect of arachidonic acid on anthralin inflammation.

    OpenAIRE

    Lawrence, C.M.; Shuster, S.

    1987-01-01

    1 The effect of topical arachidonic acid on anthralin inflammation was studied using sequential measurements of erythema (reflectance photometry) and oedema (calipers). 2 Topical arachidonic acid in concentrations which produced a small short-lived inflammatory response greatly augmented the initial phase and depressed the later phase of the inflammatory response to anthralin. 3 The initial augmentation was inhibited by concomitant administration of alpha-tocopherol. 4 It is suggested that fr...

  9. 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...

  10. Melittin stimulates phosphoinositide hydrolysis and placental lactogen release: Arachidonic acid as a link between phospholipase A sub 2 and phospholipase C signal-transduction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zeitler, P.; Handwerger, S. (Univ. of Cincinnati College of Medicine, OH (USA)); Wu, Y.Q. (Duke Univ. Medical Center, Durham, NC (USA))

    1991-01-01

    Previous investigations from this laboratory have implicated both phospholipase A{sub 2} and phospholipase C in the regulation of human placental lactogen release from human trophoblast. To study further the role of endogenous phospholipase A{sub 2} and the relationship between phospholipase A{sub 2} activation and phosphoinositide metabolism, the authors examined hPL and ({sup 3}H)-inositol release from trophoblast cells in response to agents that stimulate or inhibit the endogenous enzyme. Melittin stimulated rapid, dose-dependent, and reversible increases in the release of hPL, prostaglandin E, and ({sup 3}H)-inositol. Mepacrine inhibited this stimulation. However, mepacrine had no effect on the stimulation of hPL and ({sup 3}H)-inositol release by exogenous arachidonic acid (AA). These results indicate that the stimulation by melittin of phosphoionsitide metabolism and hPL release is mediated by initial activation of phospholipase A{sub 2}. Furthermore, the results support the possibility that AA, released as a consequence of phospholipase A{sub 2} activation, can act as a second messenger linking the two phospholipase pathways.

  11. Arachidonic acid metabolism in cultured mouse keratinocytes

    International Nuclear Information System (INIS)

    The authors attempted to characterize the general features of arachidonate metabolism in cultured mouse keratinocytes. The cells labeled with [3H]arachidonate were stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), ionophore A23187, and fetal bovine serum (FBS). Common to the three substances, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine almost equally served as sources of arachidonate liberated by the action of phospholipase A2. The stimulation of phospholipase A2 action was observed in the order of A23187 greater than FBS greater than TPA. When stimulated by TPA or A23187, the radioactivity released into the extracellular medium was mostly found in prostaglandin (PG) E2. Formation of other PGs and hydroxyeicosatetraenoate (HETE) was extremely limited. In the case of stimulation by FBS, however, the released radioactivity was mainly associated with non-converted arachidonate. FBS also inhibited the TPA- and A23187-induced conversion of arachidonate to PGE2. Phospholipid degradation induced by the three stimulators was similarly dependent on extracellular Ca2+. The stimulation by FBS and A23187 was suppressed by calmodulin antagonists, though the effect of A23187 was much more sensitive to the antagonists when compared to that of FBS. The authors observed more than additive effects of the three stimulators when tested together

  12. Maitotoxin: Effects on calcium channels, phosphoinositide breakdown, and arachidonate release in pheochromocytoma PC12 cells

    International Nuclear Information System (INIS)

    Maitotoxin (MTX) increases formation of [3H]inositol phosphates from phosphoinositides and release of [3H]arachidonic acid from phospholipids in pheochromocytoma PC12 cells. Formation of [3H]inositol phosphates is detected within 1 min of incubation even with concentrations as low as 0.3 ng/ml (90 pm) MTX, whereas release of [3H]arachidonic acid is not detected until 20 min even with concentrations as high as 1 ng/ml (300 pm) MTX. Stimulation of arachidonic acid release can be detected at 0.03 ng/ml (9 pm) MTX, whereas 0.1 ng/ml (30 pm) MTX is the threshold for detection of phosphoinositide breakdown. Organic and inorganic calcium channel blockers, except Cd2+ and a high concentration of Mn2+, have no effect on MTX-elicited phosphoinositide breakdown, whereas inorganic blockers (e.g., Co2+, Mn2+, Cd2+), but not organic blockers (nifedipine, verapamil, diltiazem), inhibit MTX-stimulated arachidonic acid release. All calcium channel blockers, however, inhibited MTX-elicited influx of 45Ca2+ and the MTX-elicited increase in internal Ca2+ measured with fura-2 was markedly reduced by nifedipine. MTX-elicited phosphoinositide breakdown and arachidonic acid release are abolished or reduced, respectively, in the absence of extracellular calcium plus chelating agent. The calcium ionophore A23187 has little or no effect alone but, in combination with MTX, A23187 inhibits MTX-elicited phosphoinositide breakdown and enhances arachidonic acid release, the latter even in the absence of extracellular calcium. The results suggest that different sites and/or mechanisms are involved in stimulation of calcium influx, breakdown of phosphoinositides, and release of arachidonic acid by MTX

  13. Arachidonic acid assimilation by thrombocytes from white carneau pigeons

    International Nuclear Information System (INIS)

    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 [14C] arachidonate in Puck's solution. After a 1 hour labeling period the WC-II cells had taken up 69% and RBWC 77% of the [14C]arachidonate from the medium. When 8,11,14-eicosatrienoic acid or 5,8,11,14,17-eicosapentaenoic acid were added to incubation media the [14C] uptake was reduced in each type cell, with WC-II exhibiting the greatest effect. Release of [14C]molecules from cells labeled with [14]Carachidonate was studied using calcium ionophore and indomethacin. Indomethacin inhibited [14C] molecule release similarly in both RBWC and WC-II cells. Calcium ionophore was twice as effective in stimulating [14C]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

  14. Involvement of Nitric Oxide on Calcium Mobilization and Arachidonic Acid Pathway Activation during Platelet Aggregation with different aggregating agonists

    OpenAIRE

    Banerjee, Debipriya; Mazumder, Sahana; Kumar Sinha, Asru

    2016-01-01

    Platelet aggregation by different aggregating agonists is essential in the normal blood coagulation process, the excess of which caused acute coronary syndrome (ACS). In all cases, the activation of arachidonic acid by cycloxygenase was needed for the synthesis of thromboxane A2 (TXA2) but the mechanism of arachidonic acid release in platelets remains obscure. Studies were conducted to determine the role of nitric oxide (NO), if any, on the release of arachidonic acid in platelets. The cytoso...

  15. Arachidonic acid metabolites in pathogenic yeasts

    Directory of Open Access Journals (Sweden)

    Ells Ruan

    2012-08-01

    Full Text Available Abstract Although most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2α and prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed.

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

    International Nuclear Information System (INIS)

    Neurotensin increased in a concentration-dependent manner the level of hypophyseal [3H]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

  17. 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)

    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 45Ca2+ uptake into the cell monolayer, and (f) increased 86Rb+ 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 Ca2+ 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 Ca2+-mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca2+ gating

  18. Growth hormone releasing factor (GRF) increases free arachidonate levels in the pituitary: a role for lipoxygenase products

    International Nuclear Information System (INIS)

    GRF, a specific stimulator of GH release, increased in a concentration- and time-dependent manner pituitary (3H)-arachidonate levels in vitro. This effect was antagonized by 100 nM somatostatin. Exogenous arachidonate also stimulated GH release in vitro. Quinacrine, a phospholipase A2 inhibitor, reduced both basal and GRF-stimulated free arachidonate levels as well as GH release. The cyclooxygenase inhibitor indomethacin was ineffective, while BW755c, which also inhibits the lipoxygenase pathway, produced a further increase in the levels of the fatty acid stimulated by GRF and potently reduced GH release. These results provide additional evidence for the involvement of arachidonate metabolism in the hormone-releasing effect of GRF at the somatotroph. 14 references, 1 figure, 2 tables

  19. The discovery and early structural studies of arachidonic acid.

    Science.gov (United States)

    Martin, Sarah A; Brash, Alan R; Murphy, Robert C

    2016-07-01

    Arachidonic acid and esterified arachidonate are ubiquitous components of every mammalian cell. This polyunsaturated fatty acid serves very important biochemical roles, including being the direct precursor of bioactive lipid mediators such as prostaglandin and leukotrienes. This 20 carbon fatty acid with four double bonds was first isolated and identified from mammalian tissues in 1909 by Percival Hartley. This was accomplished prior to the advent of chromatography or any spectroscopic methodology (MS, infrared, UV, or NMR). The name, arachidonic, was suggested in 1913 based on its relationship to the well-known arachidic acid (C20:0). It took until 1940 before the positions of the four double bonds were defined at 5,8,11,14 of the 20-carbon chain. Total synthesis was reported in 1961 and, finally, the configuration of the double bonds was confirmed as all-cis-5,8,11,14. By the 1930s, the relationship of arachidonic acid within the family of essential fatty acids helped cue an understanding of its structure and the biosynthetic pathway. Herein, we review the findings leading up to the discovery of arachidonic acid and the progress toward its complete structural elucidation. PMID:27142391

  20. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    OpenAIRE

    Nielsen, Ole H.; Bouchelouche, Pierre N.; Dag Berild

    1992-01-01

    Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l) was as potent as the calcium ionophore A23187 (10 μmol/l) for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the de...

  1. Arachidonic acid is a chemoattractant for Dictyostelium discoideum cells

    Indian Academy of Sciences (India)

    Ralph H Schaloske; Dagmar Blaesius; Christina Schlatterer; Daniel F Lusche

    2007-12-01

    Cyclic AMP (cAMP) is a natural chemoattractant of the social amoeba Dictyostelium discoideum. It is detected by cell surface cAMP receptors. Besides a signalling cascade involving phosphatidylinositol 3,4,5-trisphosphate (PIP3), Ca2+ signalling has been shown to have a major role in chemotaxis. 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 extracellular Ca2+. Here we report that AA is a chemoattractant for D. discoideum cells differentiated for 8–9 h. Motility towards a glass capillary filled with an AA solution was dose-dependent and qualitatively comparable to cAMP-induced chemotaxis. Ca2+ played an important role in AA chemotaxis of wild-type Ax2 as ethyleneglycolbis(b-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA) added to the extracellular buffer strongly inhibited motility. In the HM1049 mutant whose iplA gene encoding a putative Ins(1,4,5)P3-receptor had been knocked out, chemotaxis was only slightly affected by EGTA. Chemotaxis in the presence of extracellular Ca2+ was similar in both strains. Unlike cAMP, addition of AA to a cell suspension did not change cAMP or cGMP levels. A model for AA chemotaxis based on the findings in this and previous work is presented.

  2. Role of Arachidonic Acid in Promoting Hair Growth

    OpenAIRE

    Munkhbayar, Semchin; Jang, Sunhyae; Cho, A-Ri; Choi, Soon-Jin; Shin, Chang Yup; Eun, Hee Chul; Kim, Kyu Han; Kwon, Ohsang

    2016-01-01

    Background Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid present in all mammalian cell membranes, and involved in the regulation of many cellular processes, including cell survival, angiogenesis, and mitogenesis. The dermal papilla, composed of specialized fibroblasts located in the bulb of the hair follicle, contributes to the control of hair growth and the hair cycle. Objective This study investigated the effect of AA on hair growth by using in vivo and in vitro models. Met...

  3. Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

    Energy Technology Data Exchange (ETDEWEB)

    Schick, P.K.; Webster, P.

    1987-05-01

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

  4. Arachidonic acid metabolism in polymorphonuclear leukocytes from patients with chronic granulomatous disease.

    OpenAIRE

    Smith, D. M.; Walsh, C E; DeChatelet, L R; Waite, M.

    1983-01-01

    The effect of the calcium ionophore A23187 on the release and metabolism of [3H]arachidonic acid was examined in normal polymorphonuclear leukocytes and those obtained from patients with chronic granulomatous disease. The ionophore A23187 which stimulates oxidative metabolism in normal polymorphonuclear leukocytes was ineffective in increasing oxidative metabolism (chemiluminescence) in polymorphonuclear leukocytes from patients with chronic granulomatous disease. However, the ionophore A2318...

  5. Intracellular Actions of Group IIA Secreted Phospholipase A2 and Group IVA Cytosolic Phospholipase A2 Contribute to Arachidonic Acid Release and Prostaglandin Production in Rat Gastric Mucosal Cells and Transfected Human Embryonic Kidney Cells*

    OpenAIRE

    Ni, Zhanglin; Okeley, Nicole M.; Smart, Brian P.; Gelb, Michael H.

    2006-01-01

    Gastric epithelial cells liberate prostaglandin E2 in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-α and interleukin-1β leads to synergistic release of arachidonate and production of prostaglandin E2. Results with highly specific and potent phospholipase A2 inhibitors and with small interfering RNA show that cytosolic phospholipase A2-α and group IIA secreted phospholipase A2 ...

  6. Metabolism of arachidonic acid in phorbol ester, interferon and dimethyl sulfoxide differentiation induced U937 cells

    International Nuclear Information System (INIS)

    U937, a human macrophage cell line can metabolize arachidonic acid to a prostaglandin E2-like substance, and an unidentified lipoxygenase product. This metabolism occurs at very low levels however since these cells have low lipase and fatty acid oxygenase activities. The investigated the appearance of these enzyme activities during differentiation induced by phorbol-12-myristate-13-acetate (PMA), human gamma interferon (INF), and dimethyl sulfoxide (DMSO) on days 1,3 and 5 of stimulation using 3H-arachidonic acid (3H-AA). Culture supernatants were analyzed for free 3H-AA and 3H metabolites by radio-thin layer chromatography (3H-MET). The increasing percentage of 3H-AA release suggests the appearance of phospholipase activity during differentiation

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

    International Nuclear Information System (INIS)

    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

  8. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    Directory of Open Access Journals (Sweden)

    Ole H. Nielsen

    1992-01-01

    Full Text Available Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l was as potent as the calcium ionophore A23187 (10 μmol/l for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the decreases in radioactivity by 15.4% and 30.5%, respectively. The mechanism responsible for the release of arachidonate from cellular membranes is closely coupled to cellular calcium metabolism, and melittin was found to promote calcium entry through receptor gated calcium channels, probably due to an activation of phospholipase A2. Furthermore, a down-regulation of leukotriene B4 receptors was seen. The maximal number of binding sites per cell was reduced from a median of 1520 to 950 with melittin (1 μmol/l. The study has revealed some factors important for the inflammatory mechanisms mediated by melittin.

  9. Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment

    International Nuclear Information System (INIS)

    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 A2 (cPLA2) 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 cPLA2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA2 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 cPLA2 in the

  10. 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 (arachidonate-phospholipids and preferential reesterification of the fatty 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 for...

  11. [Changes, induced by certain flavonoids, of the hypotensive effects of arachidonic acid].

    Science.gov (United States)

    Damas, J; Mousty, J C; Lecomte, J

    1977-01-01

    In the rat, silybine and Z 12007, a derivative of rutoside, increase the vasodepressive activities of arachidonic acid, a prostaglandin precursor. They reduce the activity of PGE2. Quercetine also increases the hypotensive action of arachidonic acid. These three flavonoids are supposed to increase the prostaglandin biosynthesis. PMID:143326

  12. Involvement of Nitric Oxide on Calcium Mobilization and Arachidonic Acid Pathway Activation during Platelet Aggregation with different aggregating agonists.

    Science.gov (United States)

    Banerjee, Debipriya; Mazumder, Sahana; Kumar Sinha, Asru

    2016-03-01

    Platelet aggregation by different aggregating agonists is essential in the normal blood coagulation process, the excess of which caused acute coronary syndrome (ACS). In all cases, the activation of arachidonic acid by cycloxygenase was needed for the synthesis of thromboxane A2 (TXA2) but the mechanism of arachidonic acid release in platelets remains obscure. Studies were conducted to determine the role of nitric oxide (NO), if any, on the release of arachidonic acid in platelets. The cytosolic Ca(2+) was visualized and quantitated by fluorescent spectroscopy by using QUIN-2. NO was measured by methemoglobin method. Arachidonic acid was determined by HPLC. TXA2 was measured as ThromboxaneB2 (TXB2) by ELISA. Treatment of platelets in platelet-rich plasma (PRP) with different aggregating agents resulted in the inhibition of nitric oxide synthase (NOS) which inhibited the production of NO synthesis and increased TXA2 synthesis. Furthermore, the treatment of washed PRP with different platelet aggregating agents resulted in the increase of [Ca(2+)] in nM ranges. In contrast, the pre-treatment of washed PRP with aspirin increased platelet NO level and inhibited the Ca(2+) mobilization and TXA2 synthesis. These results indicated that the aggregation of platelets by different aggregating agonists was caused by the cytosolic Ca(2+) mobilization due to the inhibition of NOS. PMID:27127451

  13. 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.

    2011-01-01

    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

  14. The Essentiality of Arachidonic Acid in Infant Development

    Science.gov (United States)

    Hadley, Kevin B.; Ryan, Alan S.; Forsyth, Stewart; Gautier, Sheila; Salem, Norman

    2016-01-01

    Arachidonic acid (ARA, 20:4n-6) is an n-6 polyunsaturated 20-carbon fatty acid formed by the biosynthesis from linoleic acid (LA, 18:2n-6). This review considers the essential role that ARA plays in infant development. ARA is always present in human milk at a relatively fixed level and is accumulated in tissues throughout the body where it serves several important functions. Without the provision of preformed ARA in human milk or infant formula the growing infant cannot maintain ARA levels from synthetic pathways alone that are sufficient to meet metabolic demand. During late infancy and early childhood the amount of dietary ARA provided by solid foods is low. ARA serves as a precursor to leukotrienes, prostaglandins, and thromboxanes, collectively known as eicosanoids which are important for immunity and immune response. There is strong evidence based on animal and human studies that ARA is critical for infant growth, brain development, and health. These studies also demonstrate the importance of balancing the amounts of ARA and DHA as too much DHA may suppress the benefits provided by ARA. Both ARA and DHA have been added to infant formulas and follow-on formulas for more than two decades. The amounts and ratios of ARA and DHA needed in infant formula are discussed based on an in depth review of the available scientific evidence. PMID:27077882

  15. Individual variation and intraclass correlation in arachidonic acid and eicosapentaenoic acid in chicken muscle

    OpenAIRE

    Olesen Ingrid; Haug Anna; Christophersen Olav A

    2010-01-01

    Abstract Chicken meat with reduced concentration of arachidonic acid (AA) and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet. Analyses for fatty acid determination are expensive, and finding the optimal number of analyses to give reliable results is a challenge. The objective of the present study was i) to analys...

  16. Arachidonic Acid-metabolizing Cytochrome P450 Enzymes Are Targets of ω-3 Fatty Acids*

    OpenAIRE

    Arnold, Cosima; Markovic, Marija; Blossey, Katrin; Wallukat, Gerd; Fischer, Robert; Dechend, Ralf; Konkel, Anne; von Schacky, Clemens; Luft, Friedrich C.; Muller, Dominik N.; Rothe, Michael; Schunck, Wolf-Hagen

    2010-01-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against cardiovascular disease by largely unknown mechanisms. We tested the hypothesis that EPA and DHA may compete with arachidonic acid (AA) for the conversion by cytochrome P450 (CYP) enzymes, resulting in the formation of alternative, physiologically active, metabolites. Renal and hepatic microsomes, as well as various CYP isoforms, displayed equal or elevated activities when metabolizing EPA or DHA instead of AA. CYP2C/2J...

  17. Lipoxygenation of arachidonic acid by subcellular preparations from murine keratinocytes

    International Nuclear Information System (INIS)

    In these studies, we examined the possibility that cell-free preparations from murine keratinocytes possess 5-lipoxygenase activity in addition to the well-established cyclooxygenase pathway of arachidonic acid (AA) in these cells. Our data demonstrated that the high-speed (105,000 g) supernatant preparations of the murine keratinocytes metabolized [14C]AA into labeled lipoxygenase products. Portions of these radioactive metabolites cochromatographed and comigrated with 12-HETE (a marker for 12-lipoxygenase pathway) and with authentic LTB4 (a marker for 5-lipoxygenase pathway) on silicic acid column chromatography and by thin-layer chromatography (TLC) in two solvent systems respectively. Identity of the novel 14C which comigrated with LTB4 on both TLC and column chromatography was verified further by cochromatography of the free acid with authentic LTB4 on a reverse phase (RP) and the methyl esters on a straight phase high-pressure liquid chromatography. Incubation of the cell-free preparations with [14C]AA in the presence of ETYA, NDGA (inhibitors of cyclooxygenase and lipoxygenase pathways) as well as with 15-HETE (an inhibitor of lipoxygenase pathway) resulted in decreased formation of [14C] 12-HETE and the [14C]LTB4-like metabolite. On the contrary, incubations of the cell-free extracts with [14C] AA in the presence of indomethacin (a cyclooxygenase inhibitor) resulted in increased biosynthesis of the labeled lipoxygenase metabolites. These data indicate the existence of enzymes in soluble fraction of murine keratinocyte which can catalyze the transformation of [14C] AA into products of both the 12- and 5-lipoxygenase pathways

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

    International Nuclear Information System (INIS)

    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 A2 (PLA2)/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 Ca2+-mobilization and enhanced bradykinin-promoted Ca2+-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. 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)

    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 A2 activity, melittin and mastoparan, were found to increase prolactin release. Melittin also caused release of previously incorporated 3H-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 A2 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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{sub 2} activity, melittin and mastoparan, were found to increase prolactin release. Melittin also caused release of previously incorporated {sup 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{sub 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.

  1. Hyperglycemia-induced teratogenesis is mediated by a functional deficiency of arachidonic acid.

    OpenAIRE

    Goldman, A S; Baker, L; Piddington, R; Marx, B; Herold, R; Egler, J

    1985-01-01

    Congenital malformations now represent the largest single cause of mortality in the infant of the diabetic mother. The mechanism by which diabetes exerts its teratogenic effects is not known. This study evaluated whether arachidonic acid might be involved, a possibility raised by the role of arachidonic acid in palatal elevation and fusion, processes analogous to neural tube folding and fusion. This hypothesis was tested in two animal models of diabetic embryopathy, the in vivo pregnant diabe...

  2. Kinetics of uptake and distribution of arachidonic acid by rat alveolar macrophages

    International Nuclear Information System (INIS)

    The time course of uptake and distribution of 3H-arachidonic acid (3H-AA) into rat alveolar macrophage phospholipid pools was examined. Macrophages incubated with exogenous 3H-AA in RPMI-1640 containing 0.1% bovine serum albumin (BSA), incorporated this radiolabel into phosphatidylcholine and phosphatidylinositol (PI) with plateaus reached within 2 to 4 hours, which remained relatively constant for up to 18 hours. Incorporation of 3H-AA into phosphatidylethanolamine was small, but continued to increase for 14 hours. Analysis of phosphate content in phospholipid pools revealed that treatment with exogenous 5 nM arachidonic acid had no effect upon pool sizes, but there was a selective incorporation of 3H-AA into PI. Cells were incubated with 3H-AA in RPMI alone or medium containing either 0.2% lactalbumin, fetal calf serum at variable concentrations, 10% Nu Serum, or 0.1% BSA. Incubation of macrophages with 3H-AA in RPMI alone or containing 0.2% lactalbumin, resulted in approximately 70% of the radiolabel taken up by the cells being incorporated into triglyceride. The addition of BSA to RPMI-1640 medium was found to facilitate selective uptake of 3H-AA into phospholipids. Approximately 70% of incorporated 3H-AA was releasable through the action of exogenous phospholipase A2

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

    International Nuclear Information System (INIS)

    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 [3H]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 PGE2, PGF2α, and 12-HETE standards. The greatest activity corresponded to the PGE2 and PGF2α standards, which is a similar pattern to that reported for cultured human tracheal epithelium

  4. Is human colon adenocarcinoma (HT-29) proliferating activity influenced by arachidonic acid modulated metabolism in vitro after photodynamic therapy?

    International Nuclear Information System (INIS)

    Photodynamic therapy induces photo-oxidative changes of phospholipids followed by phospholipase A2 and phospholipase C activation which accelerates phospholipids degradation with polyunsaturated fatty acids eg. arachidonic acids releasing. Arachidonic acid has important role in the tumour therapy mainly as a precursor of lipids mediators - eicosanoids. The combination of indomethacin (5-100 μM) and hypericin (4 · 10-8 M) did not influence the survival of HT-29 in comparison to indomethacin and hypericin alone. On the other hand, inhibitors of lipoxygenase - NDGA (5-100 μM), MK-886 (2,5-15 μM) added 24 or 48 hours before hypericin activation showed significant antiproliferative effect in comparison to NDGA, MK-886 or hypericin alone. (authors)

  5. Arachidonic acid production by Mortierella alpina using raw crop materials

    Directory of Open Access Journals (Sweden)

    Ganggang Cao

    2015-06-01

    Full Text Available Background. Arachidonic acid (ARA is one of the three essential fatty acids, and it is important for human body to keep healthy and is widely used. At present, expensive materials such as glucose and yeast extract are generally reported to be optimal for ARA production. A new cost-effective fermentation process including cheaper material for ARA production is of great signifi cance. Material and methods. Feasibility of using corn meal and powdered soybean for fungal growth and lipid accumulation was evaluated by means of single factor test. N-hexadecane concentration was optimized, and the effect of temperature on biomass and ARA content was examined. Results. Mortierella alpina made better use of the aforementioned material as carbon and nitrogen sources for both hyphae growth and ARA production compared with glucose and yeast extract. Maximal levels of 10.9 g/L ARA and 26.1 g/L total lipids were obtained when 66 g/L corn meal, 54 g/L soybean meal and 6% (v/v n-hexadecane were supplemented. A temperature-shift strategy involved three steps, namely, 30°C (3 days – 25°C (4 days – 20°C (4 days, which further improved ARA production by 24.7%. Conclusion. Several factors such as carbon and nitrogen sources, temperature and dissolved oxygen had great infl uence on biomass and microbial oil production. Mortierella alpina preferred corn and soybean meal compared with glucose and yeast extract, which would surely alleviate the high cost of ARA production. Based on this study, the new process is both low cost and practicable.

  6. 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

    2000-01-01

    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 e

  7. Apparent in vivo retroconversion of dietary arachidonic to linoleic acid in essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.; von Wettstein-Knowles, P.

    1986-01-01

    Essential fatty acid-deficient rats were fed ethyl [U-C]arachidonate (308 dpm/nmol) and when a decrease in the transepidermal water loss was seen, the epidermal sphingolipids, acylglucosylceramide and acylceramide were isolated. [C]Linoleic acid (approx. 130 dpm/nmol) was present in both lipid...... classes, while the substrate was only detected in the former. These results intimate that in vivo retroconversion of arachidonic to linoleic acid can be induced in the rat....

  8. Effects of the oestrous cycle on the metabolism of arachidonic acid in rat isolated lung.

    Science.gov (United States)

    Bakhle, Y S; Zakrzewski, J T

    1982-01-01

    1. The metabolism of exogenous arachidonic acid perfused through the pulmonary circulation was investigated in lungs taken from rats at different stages of the oestrous cycle. 2. Following perfusion with [14C]arachidonic acid there was more radioactivity associated with cyclo-oxygenase products in general at pro-oestrus than at any other stage of the cycle. 3. Production of 6-oxo-prostaglandin F1 alpha and hence of prostacyclin (PGI2) was also highest at pro-oestrus. 4. Production of thromboxane B2 was highest at pro-oestrus although it was never greater than PGI2 production at any stage. 5. Radioactivity retained in lung tissue was mostly present in phospholipid and free fatty acid fractions with the distribution at pro-oestrus being different from the other stages. 6. Following perfusion with [14C]oleic acid (which is not a substrate for cyclooxygenase), variations in the distribution of label in radioactivity in lung were also observed. However, these were not related to the stages of the oestrous cycle in the same way as those associated with arachidonic acid. 7. We conclude that both pathways of arachidonic acid metabolism in lung--oxidation via cyclo-oxygenase and incorporation into phospholipid - are affected by the progress of the oestrous cycle. 8. Altered arachidonate metabolism appeared to be associated chiefly with pro-oestrus and may be linked to those hormones involved in this stage of the oestrous cycle. PMID:6809935

  9. 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, double-blin

  10. Stimulus-specific induction of phospholipid and arachidonic acid metabolism in human neutrophils

    International Nuclear Information System (INIS)

    Phospholipid remodeling resulting in arachidonic acid (AA) release and metabolism in human neutrophils stimulated by calcium ionophore A23187 has been extensively studied, while data obtained using physiologically relevant stimuli is limited. Opsonized zymosan and immune complexes induced stimulus-specific alterations in lipid metabolism that were different from those induced by A23187. [3H]AA release correlated with activation of phospholipase A2 (PLA2) but not with cellular activation as indicated by superoxide generation. The latter correlated more with calcium-dependent phospholipase C (PLC) activation and elevation of cellular diacylglycerol (DAG) levels. When cells that had been allowed to incorporate [3H]AA were stimulated with A23187, large amounts of labeled AA was released, most of which was metabolized to 5-HETE and leukotriene B4. Stimulation with immune complexes also resulted in the release of [3H]AA but this released radiolabeled AA was not metabolized. In contrast, stimulation with opsonized zymosan induced no detectable release of [3H]AA. Analysis of [3H]AA-labeled lipids in resting cells indicated that the greatest amount of label was incorporated into the phosphatidylinositol (PI) pool, followed closely by phosphatidylcholine and phosphatidylserine, while little [3H]AA was detected in the phosphatidylethanolamine pool. During stimulation with A23187, a significant decrease in labeled PI occurred and labeled free fatty acid in the pellet increased. With immune complexes, only a small decrease was seen in labeled PI while the free fatty acid in the pellets was unchanged. In contrast, opsonized zymosan decreased labeled PI, and increased labeled DAG. Phospholipase activity in homogenates from human neutrophils was also assayed. A23187 and immune complexes, but not zymosan, significantly enhanced PLA2 activity in the cell homogenates. On the other hand, PLC activity was enhanced by zymosan and immune complexes. (Abstract Truncated)

  11. Plasmenylethanolamine is the major storage depot for arachidonic acid in rabbit vascular smooth muscle and is rapidly hydrolyzed after angiotensin II stimulation

    International Nuclear Information System (INIS)

    The present study demonstrates that rabbit aortic intimal smooth muscle cells contain the majority of their endogenous arachidonic acid mass in plasmenylethanolamine molecular species. To demonstrate the potential significance of these plasmenylethanolamines as substrates for the smooth muscle cell phospholipases that are activated during agonist stimulation, aortic rings were prelabeled with [3H]arachidonic acid and stimulated with angiotensin II. Although the specific activities of the choline and inositol glycerophospholipid pools were similar after the labeling interval, ethanolamine glycerophospholipids had a specific activity of only 20% of the specific activity of choline and inositol glycerophospholipids. Despite the marked disparity in the specific activities of these three phospholipid classes, angiotensin II stimulation resulted in similar fractional losses (35-41%) of [3H]arachidonic acid from vascular smooth muscle choline, ethanolamine, and inositol glycerophospholipid classes. Reverse-phase HPLC demonstrated that >60% of the [3H]arachidonic acid released from ethanolamine glycerophospholipids after angiotensin II stimulation originated from plasmenylethanolamine molecular species. Taken together, the results demonstrate that the major phospholipid storage depot for arachidonic acid in vascular smooth muscle cells are plasmenylethanolamine molecular species which are important substrates for the phospholipase(s) that are activated during agonist stimulation

  12. Peroxidative metabolism of arachidonic acid in the course of Lyme arthritis

    Directory of Open Access Journals (Sweden)

    Wojciech Łuczaj

    2015-09-01

    Full Text Available [b][/b]Objective. The objective of the study was measurement of serum arachidonic acid level as well as the product of its peroxidation – 8-isoPGF[sub]2[/sub][sub]α[/sub], and the activity of phospholipase A[sub]2[/sub] and PAF-acetylhydrolase that participate in releasing 8-isoPGF[sub]2α[/sub] from glycerol skeleton, and the potential designation of their role in the pathomechanism of Lyme disease (LD. Material and methods. Changes in the phospholipid arachidonic acid level and the level of 8-isoPGF[sub]2α[/sub] were determined in the plasma and urine of patients with LA (n=57 and of healthy controls (n=41. The activity of phospholipase A[sub]2[/sub] and PAF acetylhydrolase were assayed. All examined parameters were also measured in the plasma of some LA patients (n=13 after antibiotics treatment. Results. An almost 3-fold higher level of the total plasma 8-isoPGF[sub]2α[/sub] was observed in LA patients compared to the controls, while in the urine it increased over 5-fold. The plasma PLA[sub]2[/sub] activity was more than 3-fold higher in LA patients than in the healthy subjects, while PAF acetylhydrolase activity was observed to be modestly, but not significantly lower. The total 8-isoPGF[sub]2α[/sub] level in the plasma and urine of LA patients was significantly lower after antibiotics treatment. The plasma activity of PAF-AH in the LA patients was increased, while the cPLA[sub]2[/sub] activity decreased after antibiotics treatment. Conclusions. It may be suggested that in the course of LA, the level of binding 8-isoPGF[sub]2α[/sub] is significantly enhanced, and it may also be suggested that uncontrolled changes in the lipid status of some patients may make their Lyme arthritis unresponsive to antibiotics.

  13. Dietary supplementation with arachidonic acid in tilapia (Oreochromis mossambicus) reveals physiological effects not mediated by prostaglandins.

    NARCIS (Netherlands)

    Anholt, R.D. van; Spanings, F.A.T.; Koven, W.M.; Wendelaar Bonga, S.E.

    2004-01-01

    This study aims to clarify the role of the polyunsaturated fatty acid arachidonic acid (ArA, 20:4n-6) in the stress response of Mozambique tilapia (Oreochromis mossambicus). ArA is converted into eicosanoids, including prostaglandins, which can influence the response to stressors. Tilapia, a species

  14. Evidence for lipoxin formation by bovine polymorphonuclear leukocytes via triple dioxygenation of arachidonic acid

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Walstra, P.; Verhagen, J.; Vermeer, M.A.; Klerks, J.P.M.; Veldink, G.A.

    1988-01-01

    Incubation of bovine polymorphonuclear leukocytes (PMNs) with arachidonic acid leads to the formation of four lipoxins. The same lipoxins are also formed upon incubation of bovine PMNs with 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, 5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic aci

  15. Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

    Directory of Open Access Journals (Sweden)

    Messamore Erik

    2016-01-01

    Full Text Available This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels in the skin. A blunted skin flush response to niacin is reliably observed among patients with schizophrenia. The niacin response abnormality may thus serve as a biomarker to identify a physiological subtype of schizophrenia associated with defective arachidonic acid-derived signaling.

  16. Differences in the effect of arachidonic acid on polymorphonuclear and mononuclear leukocyte function

    OpenAIRE

    Nijkamp, F.P.; Henricks, P.A.J.; Tol, M.E. van der; Kats-Renaud, J. H. van; Verhoef, J.

    1984-01-01

    Incubation of human polymorphonuclear leukocytes with arachidonic acid resulted in a stimulation of the oxidative metabolism of the cells. Upon stimulation with 80 μM arachidonic acid, neutrophils (5·106 cells/ml) produced superoxide (53±8 nmol/5·106 cells per 15 min), generated chemiluminescence (1211 100±157 000 cpm) and consumed oxygen (20±1 nmol/106 cells per 5 min). The stimulation of the cell metabolism could be reduced 40–60% by prior incubation of the cells with 10 μM indomethacin. In...

  17. Mechanism of arachidonic acid liberation in platelet-activating factor-stimulated human polymorphonuclear neutrophils

    International Nuclear Information System (INIS)

    Upon stimulation of human polymorphonuclear neutrophils with platelet-activating factor (PAF), arachidonic acid (AA) is released from membrane phospholipids. The mechanism for AA liberation, a key step in the synthesis of biologically active eicosanoids, was investigated. PAF was found to elicit an increase in the cytoplasmic level of free Ca2+ as monitored by fluorescent indicator fura 2. When [3H] AA-labeled neutrophils were exposed to PAF, the enhanced release of AA was observed with a concomitant decrease of radioactivity in phosphatidylinositol and phosphatidylcholine fractions. The inhibitors of phospholipase A2, mepacrine and 2-(p-amylcinnamoyl)-amino-4-chlorobenzoic acid, effectively suppressed the liberation of [3H]AA from phospholipids, indicating that liberation of AA is mainly catalyzed by the action of phospholipase A2. The extracellular Ca2+ is not required for AA release. However, intracellular Ca2+ antagonists, TMB-8 and high dose of quin 2/AM drastically reduced the liberation of AA induced by PAF, indicating that Ca2+ is an essential factor for phospholipase A2 activation. PAF raised the fluorescence of fura 2 at concentrations as low as 8 pM which reached a maximal level about 8 nM, whereas more than nM order concentrations of PAF was required for the detectable release of [3H]AA. Pretreatment of neutrophils with pertussis toxin resulted in complete abolition of AA liberation in response to PAF. However, the fura 2 response to PAF was not effectively inhibited by toxin treatment. In human neutrophil homogenate and membrane preparations, guanosine 5'-O-(thiotriphosphate) stimulated AA release and potentiated the action of PAF. Guanosine 5'-O-(thiodiphosphate) inhibited the effects of guanosine 5'-O-(thiotriphosphate)

  18. Dietary arachidonic acid and docosahexaenoic acid regulate liver fatty acid desaturase (FADS) alternative transcript expression in suckling piglets

    OpenAIRE

    Wijendran, Vasuki; Downs, Ian; Tyburczy, Cynthia; Kothapalli, Kumar S. D.; Park, Woo Jung; Blank, Bryant S.; Zimmer, J. Paul; Butt, C. M.; Salem, Norman; Brenna, J. Thomas

    2013-01-01

    Molecular regulation of fatty acid desaturase (Fads) gene expression by dietary arachidonic (ARA) and docosahexaenoic acid (DHA) during early postnatal period, when the demand for long chain polyunsaturated fatty acids (LC-PUFA) is very high, has not been well defined. The objective of the current study was to determine regulation of liver Fads1, Fads2 and Fads3 classical (CS) and alternative transcripts (AT) expression by dietary ARA and DHA, within the physiological range present in human b...

  19. Unexpected depletion of plasma arachidonate and total protein in cats fed a low arachidonic acid diet due to peroxidation.

    Science.gov (United States)

    Chamberlin, Amy; Mitsuhashi, Yuka; Bigley, Karen; Bauer, John E

    2011-10-01

    An opportunity to investigate a low-arachidonic acid (AA) feline diet possibly related to elevated peroxide value (PV) during storage on plasma phospholipid (PL) and reproductive tissue fatty acid (FA) profiles presented itself in the present study. Cats (nine animals per group) had been fed one of three dry extruded, complete and balanced diets for 300 d before spaying. The diets contained adequate AA (0.3 g/kg), similar concentration of antioxidants and were stored at ambient temperature, but differed in FA composition. The diets were designated as follows: diet A (high linoleic acid), diet B (high γ-linolenic acid) and diet C (adequate linoleic acid). Diet samples that were obtained the week before spaying revealed an elevated PV of diet A v. diets B and C (135 v. 5.80 and 2.12 meq/kg fat, respectively). Records revealed decreased food consumption of diet A cats beginning at 240 d but without weight loss; thus an opportunity presented to investigate diet PV effects. Total plasma protein and PL-AA concentrations in group A were significantly decreased at 140 and 300 d. Uterine and ovarian tissues collected at surgery revealed modest decrements of AA. Diet A was below minimum standards at 0.015 % (minimum 0.02 %), probably due to oxidation. The time at which diet A became unacceptable may have occurred between 60 and 140 d because plasma PL-AA was within our normal colony range (approximately 4-7 % relative) after 56 d of feeding. High-linoleic acid-containing diets may be more likely to be oxidised requiring additional antioxidants. The findings suggest that reduced plasma protein in combination with plasma AA concentrations may serve as biomarkers of diet peroxidation in cats before feed refusal, weight loss or tissue depletion. PMID:22005409

  20. Myogenic and metabolic feedback in cerebral autoregulation: Putative involvement of arachidonic acid-dependent pathways.

    Science.gov (United States)

    Berg, Ronan M G

    2016-07-01

    The present paper presents a mechanistic model of cerebral autoregulation, in which the dual effects of the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) on vascular smooth muscle mediate the cerebrovascular adjustments to a change in cerebral perfusion pressure (CPP). 20-HETE signalling in vascular smooth muscle mediates myogenic feedback to changes in vessel wall stretch, which may be modulated by metabolic feedback through EETs released from astrocytes and endothelial cells in response to changes in brain tissue oxygen tension. The metabolic feedback pathway is much faster than 20-HETE-dependent myogenic feedback, and the former thus initiates the cerebral autoregulatory response, while myogenic feedback comprises a relatively slower mechanism that functions to set the basal cerebrovascular tone. Therefore, assessments of dynamic cerebral autoregulation, which may provide information on the response time of the cerebrovasculature, may specifically be used to yield information on metabolic feedback mechanisms, while data based on assessments of static cerebral autoregulation represent the integrated functionality of myogenic and metabolic feedback. PMID:27241246

  1. Prenatal arachidonic acid exposure and selected immune-related variables in childhood

    NARCIS (Netherlands)

    Dirix, Chantal E. H.; Hogervorst, Janneke G. F.; Rump, Patrick; Hendriks, Johannes J. E.; Bruins, Maaike; Hornstra, Gerard

    2009-01-01

    Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childho

  2. In vitro prostaglandin biosynthesis in human pregnant uterus from arachidonic acid

    International Nuclear Information System (INIS)

    Formation of prostaglandins (Fsub(2α), E2 and D2) in the pregnant human uterus microsomes was studied using 14C-labelled arachidonic acid. Sample of uterine pieces were removed from the lower uterine segment at the time of Caesarean section. The prostaglandin synthesis in the microsomal fraction was characterized in terms of cofactors, substrate concentration and incubation time requirements. (author)

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

    International Nuclear Information System (INIS)

    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

  4. Phosphate limitation promotes unsaturated fatty acids and arachidonic acid biosynthesis by microalgae Porphyridium purpureum.

    Science.gov (United States)

    Su, Gaomin; Jiao, Kailin; Li, Zheng; Guo, Xiaoyi; Chang, Jingyu; Ndikubwimana, Theoneste; Sun, Yong; Zeng, Xianhai; Lu, Yinghua; Lin, Lu

    2016-07-01

    Polyunsaturated fatty acids (PUFAs) are highly appreciated on their nutritive value for human health and aquaculture. P. purpureum, one of the red microalgae acknowledged as a promising accumulator of ARA, was chosen as the target algae in the present research. Effects of sodium bicarbonate (0.04-1.2 g/L), temperature (25, 30 and 33 °C) and phosphate (0.00-0.14 g/L) on biomass yield, total fatty acids (TFA) and arachidonic acid (ARA) accumulation were investigated systemically. NaHCO3 dose of 0.8 g/L and moderate temperature of 30 °C were preferred. In addition, TFA and ARA production were significantly enhanced by an appropriate concentration of phosphate, and the highest TFA yield of 666.38 mg/L and ARA yield of 159.74 mg/L were obtained at a phosphate concentration of 0.035 g/L. Interestingly, with phosphate concentration continuing to fall, UFA/TFA and ARA/EPA ratios were increased accordingly, suggesting that phosphate limitation promoted unsaturated fatty acids and arachidonic acid biosynthesis. Low concentration of phosphate may be favored to increase the enzymatic activities of ∆6-desaturase, which played a key role in catalyzing the conversion of C16:0 to C18:2, and thus the selectivity of UFA increased. Meanwhile, the increase of ARA selectivity could be attributed to ω6 pathway promotion and ∆17-desaturase activity inhibition with phosphate limitation. Phosphate limitation strategy enhanced unsaturated fatty acids and ARA biosynthesis in P. purpureum, and can be applied in commercial scale manufacturing and commercialization of ARA. PMID:27004948

  5. Melittin stimulates fatty acid release through non-phospholipase-mediated mechanisms and interacts with the dopamine transporter and other membrane spanning proteins

    OpenAIRE

    Keith, Dove J; Eshleman, Amy J; Janowsky, Aaron

    2010-01-01

    Phospholipase A2 releases the fatty acid arachidonic acid from membrane phospholipids. We used the purported phospholipase A2 stimulator, melittin, to examine the effects of endogenous arachidonic acid signaling on dopamine transporter function and trafficking. In HEK-293 cells stably transfected with the dopamine transporter, melittin reduced uptake of [3H]dopamine. Additionally, measurements of fatty acid content demonstrated a melittin-induced release of membrane-incorporated arachidonic a...

  6. Metabolism of arachidonic acid in hamster lung microsomes is not completely inhibited by aspirin and indomethacin

    Energy Technology Data Exchange (ETDEWEB)

    Uotila, P.; Paajanen, H.; Schalin, M.; Simberg, N.

    1983-10-01

    Aspirin (100 microM or 1 mM) or indomethacin (10 microM or 100 microM) was incubated with a microsomal preparation of hamster lungs in the presence of NADPH for 10 min. Then 14C-arachidonic acid (20 microM) was added and the incubation was continued for an additional 20 min. The metabolites were extracted with ethyl acetate first at pH 7.4 and then at pH 3.5 and analysed by thin layer chromatography. Both aspirin and indomethacin inhibited dose dependently the formation of all identified prostaglandins, including PGF2 alpha, 6-keto-PGF1 alpha, PGE2 and PGD2. The rate of formation of some unidentified metabolites extracted at pH 7.4 and 3.5 was, however, not changed by aspirin or indomethacin. We have earlier reported that in isolated perfused hamster lungs the formation of all arachidonate metabolites is inhibited by both aspirin and indomethacin. As the present study indicates that in the microsomes of hamster lungs all metabolic pathways of arachidonic acid are not inhibited by aspirin or indomethacin, it is possible that in isolated tissues and in vivo aspirin-like drugs have some other inhibitory effects on arachidonate metabolism than the inhibition of the cyclo-oxygenase enzyme.

  7. Anti-inflammatory potential of 2-styrylchromones regarding their interference with arachidonic acid metabolic pathways

    OpenAIRE

    Gomes, Ana; Fernandes, Eduarda; Silva, Artur; Santos, Clementina M.M.; Pinto, Diana; Cavaleiro, José; Lima, José Costa

    2009-01-01

    Abstract Cyclooxygenases (COXs) are the key enzymes in the biosynthesis of prostanoids. COX-1 is a constitutive enzyme while the expression of COX-2 is highly stimulated in the event of inflammatory processes, leading to the production of large amounts of prostaglandins (PGs), in particular PGE2 and PGI2, which are pro-inflammatory mediators. Lipoxygenases (LOXs) are enzymes that produce hydroxy acids and leukotrienes (LTs). 5-LOX metabolizes arachidonic acid to yield, a...

  8. Contact sensitizers modulate the arachidonic acid metabolism of PMA-differentiated U-937 monocytic cells activated by LPS.

    Science.gov (United States)

    Del Bufalo, Aurélia; Bernad, José; Dardenne, Christophe; Verda, Denis; Meunier, Jean Roch; Rousset, Françoise; Martinozzi-Teissier, Silvia; Pipy, Bernard

    2011-10-01

    For the effective induction of a hapten-specific T cell immune response toward contact sensitizers, in addition to covalent-modification of skin proteins, the redox and inflammatory statuses of activated dendritic cells are crucial. The aim of this study was to better understand how sensitizers modulate an inflammatory response through cytokines production and COX metabolism cascade. To address this purpose, we used the human monocytic-like U-937 cell line differentiated by phorbol myristate acetate (PMA) and investigated the effect of 6 contact sensitizers (DNCB, PPD, hydroquinone, propyl gallate, cinnamaldehyde and eugenol) and 3 non sensitizers (lactic acid, glycerol and tween 20) on the production of pro-inflammatory cytokines (IL-1β and TNF-α) and on the arachidonic acid metabolic profile after bacterial lipopolysaccharide (LPS) stimulation. Our results showed that among the tested molecules, all sensitizers specifically prevent the production of PMA/LPS-induced COX-2 metabolites (PGE(2,) TxB(2) and PGD(2)), eugenol and cinnamaldehyde inhibiting also the production of IL-1β and TNF-α. We further demonstrated that there is no unique PGE(2) inhibition mechanism: while the release of arachidonic acid (AA) from membrane phospholipids does not appear do be a target of modulation, COX-2 expression and/or COX-2 enzymatic activity are the major steps of prostaglandin synthesis that are inhibited by sensitizers. Altogether these results add a new insight into the multiple biochemical effects described for sensitizers. PMID:21807015

  9. Stimulation of arachidonic acid metabolism in primary cultures of osteoblast-like cells by hormones and drugs

    International Nuclear Information System (INIS)

    The effects of parathyroid hormone (PTH), dihydroxycholecalciferol (1,25-(OH)2 D3), thrombin, epidermal growth factor (EGF) and 12-o-tetradecanoylphorbol-13-acetate (PMA) on the biosynthesis and release of arachidonic acid metabolites were studied in primary cultures of osteoblast-like cells isolated from 18-day-old chick embryo calvaria. Cells were labelled with (14C)-arachidonic acid for 30 h. The radioactive eicosanoids were extracted from the cell culture media after a further 30 h stimulation period and analysed on a PRP-1 column by HPLC. The radioactive products were characterized by co-elution of (3H) standard prostanoids. Osteoblasts showed a basal release of the prostanoids 6-keto-PGF1 alpha, TXB2, PGF2 alpha, PGE2, PGD2 and PGB2, the latter being the most abundant one. Indomethacin (10(-5) M) effectively inhibited the basal release, but not that of an as yet unidentified compound. The release of prostanoids was stimulated by PTH (2 U/ml), thrombin (0.4 NIH/ml), EGF (50 ng/ml) and PMA (25 ng/ml), the latter being by far the most potent one. 1,25-(OH)2D3 was found to slightly inhibit the prostanoid release. These results indicate: (1) primary cultures of osteoblasts synthesize several prostaglandins, thromboxane B2 and one unidentified product. (2) the action on bone of PTH and the various drugs tested may be, at least partly, mediated by an increased prostaglandin production by osteoblasts. Clearly this does not apply to 1,25-(OH)2D3

  10. Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

    OpenAIRE

    Hyde, C. A. C.; Missailidis, S

    2009-01-01

    Arachidonic acid (AA) and its metabolites have recently generated a heightened interest due to growing evidence of their significant role in cancer biology. Thus, inhibitors of the AA cascade, first and foremost COX inhibitors, which have originally been of interest in the treatment of inflammatory conditions and certain types of cardiovascular disease, are now attracting attention as an arsenal against cancer. An increasing number of investigations support their role in cancer chemopreventio...

  11. 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.

  12. Increased cell membrane arachidonic acid in experimental colorectal tumours.

    OpenAIRE

    Nicholson, M. L.; Neoptolemos, J P; Clayton, H A; Talbot, I C; Bell, P R

    1991-01-01

    Tumour cell membrane fatty acid composition was investigated using an animal model of colorectal carcinogenesis. Eighty six male Wistar rats were fed experimental diets containing either 5% saturated fat or 20% saturated fat. Colorectal tumours were induced by intraperitoneal injection of azoxymethane, and control rats received saline. Animals were killed at intervals up to 26 weeks after the last injection of carcinogen for histology and lipid analysis. Cell membrane fatty acids in colonic m...

  13. Targeted Chiral Analysis of Bioactive Arachidonic Acid Metabolites Using Liquid-Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Clementina Mesaros

    2012-04-01

    Full Text Available A complex structurally diverse series of eicosanoids arises from the metabolism of arachidonic acid. The metabolic profile is further complicated by the enantioselectivity of eicosanoid formation and the variety of regioisomers that arise. In order to investigate the metabolism of arachidonic acid in vitro or in vivo, targeted methods are advantageous in order to distinguish between the complex isomeric mixtures that can arise by different metabolic pathways. Over the last several years this targeted approach has become more popular, although there are still relatively few examples where chiral targeted approaches have been employed to directly analyze complex enantiomeric mixtures. To efficiently conduct targeted eicosanoid analyses, LC separations are coupled with collision induced dissociation (CID and tandem mass spectrometry (MS/MS. Product ion profiles are often diagnostic for particular regioisomers. The highest sensitivity that can be achieved involves the use of selected reaction monitoring/mass spectrometry (SRM/MS; whereas the highest specificity is obtained with an SRM transitions between an intense parent ion, which contains the intact molecule (M and a structurally significant product ion. This review article provides an overview of arachidonic acid metabolism and targeted chiral methods that have been utilized for the analysis of the structurally diverse eicosanoids that arise.

  14. Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder.

    Science.gov (United States)

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Stanford, Kevin E; Hahn, Chang-Gyu; Richtand, Neil M

    2008-09-30

    Previous antemortem and postmortem tissue fatty acid composition studies have observed significant deficits in the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3) in red blood cell (RBC) and postmortem cortical membranes of patients with unipolar depression. In the present study, we determined the fatty acid composition of postmortem orbitofrontal cortex (OFC, Brodmann area 10) of patients with bipolar disorder (n=18) and age-matched normal controls (n=19) by gas chromatography. After correction for multiple comparisons, DHA (-24%), arachidonic acid (-14%), and stearic acid (C18:0) (-4.5%) compositions were significantly lower, and cis-vaccenic acid (18:1n-7) (+12.5%) composition significantly higher, in the OFC of bipolar patients relative to normal controls. Based on metabolite:precursor ratios, significant elevations in arachidonic acid, stearic acid, and palmitic acid conversion/metabolism were observed in the OFC of bipolar patients, and were inversely correlated with DHA composition. Deficits in OFC DHA and arachidonic acid composition, and elevations in arachidonic acid metabolism, were numerically (but not significantly) greater in drug-free bipolar patients relative to patients treated with mood-stabilizer or antipsychotic medications. OFC DHA and arachidonic acid deficits were greater in patients plus normal controls with high vs. low alcohol abuse severity. These results add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of bipolar disorder. PMID:18715653

  15. Arachidonic acid needed in infant formula when docosahexaenoic acid is present.

    Science.gov (United States)

    Brenna, J Thomas

    2016-05-01

    Recently, the European Food Safety Authority asserted that arachidonic acid (ARA) is an optional nutrient for the term infant even when docosahexaenoic acid (DHA) is present. The brief rationale is based on an explicit, widespread misapplication of the concept of "essential fatty acids" to linoleic acid that implies it is uniquely required as a nutrient per se. Linoleic acid prevents acute clinical symptoms caused by polyunsaturated fatty acid-deficient diets and is the major precursor for ARA in most human diets. Experimental diets with ARA as the sole n-6 similarly prevent symptoms but at a lower energy percentage than linoleic acid and show ARA is a precursor for linoleic acid. The absence of consistent evidence of ARA benefit from randomized controlled trials is apparently an issue as well. This review highlights basic and clinical research relevant to ARA requirements as an adjunct to DHA in infancy. ARA is a major structural central nervous system component, where it rapidly accumulates perinatally and is required for signaling. Tracer studies show that ARA-fed infants derive about half of their total body ARA from dietary preformed ARA. Clinically, of the 3 cohorts of term infants studied with designs isolating the effects of ARA (DHA-only vs DHA+ARA), none considered ARA-specific outcomes such as vascular or immune function; the study with the highest ARA level showed significant neurocognitive benefit. All breastfed term infants of adequately nourished mothers consume both DHA and ARA. The burden of proof to substantially deviate from the composition of breastmilk is greater than that available from inherently empirical human randomized controlled trial evidence. Infant formulas with DHA but without ARA risk harm from suppression of ARA-mediated metabolism manifest among the many unstudied functions of ARA. PMID:27013482

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

    International Nuclear Information System (INIS)

    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 Ca2+-independent, but not Ca2+-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 Ca2+-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.

  17. Individual variation and intraclass correlation in arachidonic acid and eicosapentaenoic acid in chicken muscle

    Directory of Open Access Journals (Sweden)

    Olesen Ingrid

    2010-04-01

    Full Text Available Abstract Chicken meat with reduced concentration of arachidonic acid (AA and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet. Analyses for fatty acid determination are expensive, and finding the optimal number of analyses to give reliable results is a challenge. The objective of the present study was i to analyse the intraclass correlation of different fatty acids in five meat samples, of one gram each, within the same chicken thigh, and ii to study individual variations in the concentrations of a range of fatty acids and the ratio between omega-6 and omega-3 fatty acid concentrations among fifteen chickens. Fifteen newly hatched broilers were fed a wheat-based diet containing 4% rapeseed oil and 1% linseed oil for three weeks. Five muscle samples from the mid location of the thigh of each chicken were analysed for fatty acid composition. The intraclass correlation (sample correlation within the same animal was 0.85-0.98 for the ratios of total omega-6 to total omega-3 fatty acids and of AA to eicosapentaenoic acid (EPA. This indicates that when studying these fatty acid ratios, one sample of one gram per animal is sufficient. However, due to the high individual variation between chicken for these ratios, a relatively high number of animals (minimum 15 are required to obtain a sufficiently high power to reveal significant effects of experimental factors (e.g. feeding regimes. The present experiment resulted in meat with a favorable concentration ratio between omega-6 and omega-3 fatty acids. The AA concentration varied from 1.5 to 2.8 g/100 g total fatty acids in thigh muscle in the fifteen broilers, and the ratio between AA and EPA concentrations ranged from 2.3 to 3.9. These differences among the birds may be due to genetic variance that can be exploited by

  18. Arachidonic and eicosapentaenoic acid metabolism in bovine neutrophils and platelets: effect of calcium ionophore

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, S.M.; Laegreid, W.W.; Heidel, J.R.; Straub, K.M.; Liggitt, H.D.; Silflow, R.M.; Breeze, R.G.; Leid, R.W.

    1987-09-01

    Substitution of dietary fatty acids has potential for altering the inflammatory response. The purpose of the present study was to define the metabolites of arachidonic acid (AA) and eicosapentaenoic acid (EPA) secreted by bovine peripheral blood neutrophils and platelets. High performance liquid chromatography was used to characterize cyclooxygenase and lipoxygenase metabolites secreted in response to the calcium ionophore A23187. Cells were prelabelled with /sup 3/H-AA or /sup 3/H-EPA prior to challenge with the calcium ionophore. Bovine neutrophils secreted leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) as the major metabolites of AA, as well as the corresponding leukotriene B5 (LTB5) and 5-hydroxyeicosapentaenoic acid (5-HEPE) metabolites of EPA. Peptidoleukotrienes derived from /sup 3/H-AA or /sup 3/H-EPA were not detected under these conditions. The major tritiated metabolites secreted from bovine platelets were: thromboxane A2, measured as the stable metabolite thromboxane B2 (TXB2); hydroxyheptadecatrienoic acid (HHT) and 12-HETE derived from /sup 3/H-AA; and the omega-3 analogs TXB3 and 12-HEPE, derived from /sup 3/H-EPA. Preferred substrate specificities existed amongst the AA- and EPA-derived metabolites for the intermediary enzymes involved in the arachidonic acid cascade. These findings support the hypothesis that substitution of membrane-bound AA by EPA has potential for modulation of the host inflammatory response following cellular phospholipid mobilization.

  19. Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for Intracellular Arachidonic Acid Metabolism

    Science.gov (United States)

    Toledo, Daniel A. M.; Roque, Natália R.; Teixeira, Lívia; Milán-Garcés, Erix A.; Carneiro, Alan B.; Almeida, Mariana R.; Andrade, Gustavo F. S.; Martins, Jefferson S.; Pinho, Roberto R.; Freire-de-Lima, Célio G.; Bozza, Patrícia T.; D’Avila, Heloisa

    2016-01-01

    Most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions termed lipid bodies (LBs) or lipid droplets (LDs). In mammalian cells, such as macrophages, these lipid-rich organelles are formed in response to host-pathogen interaction during infectious diseases and are sites for biosynthesis of arachidonic acid (AA)-derived inflammatory mediators (eicosanoids). Less clear are the functions of LBs in pathogenic lower eukaryotes. In this study, we demonstrated that LBs, visualized by light microscopy with different probes and transmission electron microscopy (TEM), are produced in trypomastigote forms of the parasite Trypanosoma cruzi, the causal agent of Chagas’ disease, after both host interaction and exogenous AA stimulation. Quantitative TEM revealed that LBs from amastigotes, the intracellular forms of the parasite, growing in vivo have increased size and electron-density compared to LBs from amastigotes living in vitro. AA-stimulated trypomastigotes released high amounts of prostaglandin E2 (PGE2) and showed PGE2 synthase expression. Raman spectroscopy demonstrated increased unsaturated lipid content and AA incorporation in stimulated parasites. Moreover, both Raman and MALDI mass spectroscopy revealed increased AA content in LBs purified from AA-stimulated parasites compared to LBs from unstimulated group. By using a specific technique for eicosanoid detection, we immunolocalized PGE2 within LBs from AA-stimulated trypomastigotes. Altogether, our findings demonstrate that LBs from the parasite Trypanosoma cruzi are not just lipid storage inclusions but dynamic organelles, able to respond to host interaction and inflammatory events and involved in the AA metabolism. Acting as sources of PGE2, a potent immunomodulatory lipid mediator that inhibits many aspects of innate and adaptive immunity, newly-formed parasite LBs may be implicated with the pathogen survival in its host. PMID:27490663

  20. Inability of murine peritoneal macrophages to convert linoleic acid into arachidonic acid. Evidence of chain elongation

    International Nuclear Information System (INIS)

    Various murine macrophage populations synthesize and secrete large amounts of arachidonic acid (20:4n-6) derived eicosanoids (cyclo-oxygenase and lipoxygenase products). These metabolites are known to possess a wide variety of functions with regard to the initiation and regulation of inflammation and tumorigenesis. Because the dietary intake of 20:4n-6 is usually low, tissues are largely dependent upon dietary linoleic acid (18:2n-6) as an initial unsaturated precursor for the biosynthesis of 20:4n-6. The purpose of these experiments was to determine whether resident or responsive murine macrophages possess desaturase and elongase activities capable of in vitro conversion of 18:2n-6 into 20:4n-6. Peritoneal exudate macrophages were purified by adherence and incubated in serum-free medium containing fatty acid-free BSA with [1-14C] 18:2n-6. Approximately 90 to 98% of the [14C]18:2n-6 at 4 and 16 h was recovered in phosphatidylcholine and phosphatidylethanolamine. The metabolism of [14C]18:2n-6 was determined after transesterification and separation of the 14C-fatty acid methyl esters by argentation TLC, reverse phase HPLC, and electron impact gas chromatography/mass spectrometry. Resident and responsive macrophages lacked the capacity to transform [14C]18:2n-6 into 20:4n-6. In addition, prelabeled macrophages incubated with soluble, calcium ionophore A23187 or phorbol myristate, or particulate, zymosan, membrane perturbing agents also lacked delta 6 desaturase activity. All macrophages tested were capable of elongating [14C]18:2n-6 into [14C]20:2n-6. These observations suggest that 20:4n-6, present in macrophage phospholipids, is biosynthesized elsewhere and transported to the macrophage for esterification into the phospholipids. In addition, these findings demonstrate that elongase activity is present in both the resident and responsive peritoneal macrophage

  1. PHYSIOLOGICAL INHIBITORY EFFECT OF OCS IN ARACHIDONIC ACID-RICH PARIETOCHLORIS INCISA (TREBOUXIOPHYCEAE, CHLOROPHYTA)

    Institute of Scientific and Technical Information of China (English)

    刘建国; 张成武; ZviCohen; AmosRichmond

    2002-01-01

    Parietochloris incisa is an arachidonic acid-rich snow green alga. The main physiological profiles, such as ash free dry weight (AFDW), chlorophyll, carotenoid, protein and total fatty acids (TFA), in this alga exposed to old culture supernatant (OCS) at the decline phase or its crude ethyl acetate extracts (CEAE) were investigated by using tubular photobioreactors of different diameters. Results showed that both OCS and CEAE had strong inhibitory effect on the above physiological parameters. The longer the culture was exposed to OCS and the more CEAE were added into the algal culture, the more the above physiological properties were inhibited. Arachidonic acid (AA), the dominant component of fatty acids in this alga, was also seriously inhibited with respect to total TFA, AFDW of cell mass, or culture volume, due to a prebable reduction of enzymes activities catalyzing chain elongation from C18:1ω9 to AA. These results incontestably evidenced that some CEAE dissolving substances existing in OCS, like auto-inhibitors, inhibited P. incisa growth through feedback. Hence, any efficient removal of auto-inhibitors from algal culture to decrease their bioactivity could be good for maximal production of desired products like AA.

  2. PHYSIOLOGICAL INHIBITORY EFFECT OF OCS IN ARACHIDONIC ACID-RICH PARIETOCHLORIS INCISA (TREBOUXIOPHYCEAE,CHLOROPHYTA)

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Parietochloris incisa is an arachidonic acid-rich snow green alga. The main phy siological profiles, such as ash free dry weight (AFDW), chlorophyll, carotenoid , protein and total fatty acids (TFA), in this alga exposed to old culture super natant (OCS) at the decline phase or its crude ethyl acetate extracts (CEAE) wer e investigated by using tubular photobioreactors of different diameters. Results showed that both OCS and CEAE had strong inhibitory effect on the above physiol ogical parameters. The longer the culture was exposed to OCS and the more CEAE w ere added into the algal culture, the more the above physiological properties we re inhibited. Arachidonic acid (AA), the dominant component of fatty acids in th is alga, was also seriously inhibited with respect to total TFA, AFDW of cell ma ss, or culture volume, due to a probable reduction of enzymes activities catalyz ing chain elongation from C18:1ω9 to AA. These results incontestably evidenced t hat some CEAE dissolving substances existing in OCS, like auto-inhibitors, inhi bited P. incisa growth through feedback. Hence, any efficient removal of aut o-i nhibitors from algal culture to decrease their bioactivity could be good for max imal production of desired products like AA.

  3. Release of arachidonate from membrane phospholipids in cultured neonatal rat myocardial cells during adenosine triphosphate depletion. Correlation with the progression of cell injury.

    OpenAIRE

    Chien, K R; Sen, A; Reynolds, R.; Chang, A.; Kim, Y; M. D. Gunn; Buja, L. M.; Willerson, J T

    1985-01-01

    The present study utilized a cultured myocardial cell model to evaluate the relationship between the release of arachidonate from membrane phospholipids, and the progression of cell injury during ATP depletion. High-energy phosphate depletion was induced by incubating cultured neonatal rat myocardial cells with various combinations of metabolic inhibitors (deoxyglucose, oligomycin, cyanide, and iodoacetate). Phospholipid degradation was assessed by the release of radiolabeled arachidonate fro...

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

    Science.gov (United States)

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

    2011-11-01

    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 that corresponded with no decrease in mRBC-DHA during pregnancy, or in infant (i) RBC-DHA or mRBC-DHA during the first 3 months postpartum (DHA-equilibrium) while exclusively breastfeeding. At delivery, iRBC-AA is uniformly high and independent of mRBC-AA. Infants born to mothers with low RBC-DHA exhibit higher, but infants born to mothers with high RBC-DHA exhibit lower RBC-DHA than their mothers. This switch from 'biomagnification' into 'bioattenuation' occurs at 6g% mRBC-DHA. At 6g%, mRBC-DHA is stable throughout pregnancy, corresponds with postpartum infant DHA-equilibrium of 6 and 0.4g% DHA in mature milk, but results in postpartum depletion of mRBC-DHA to 5g%. Postpartum maternal DHA-equilibrium is reached at 8g% mRBC-DHA, corresponding with 1g% DHA in mature milk and 7g% iRBC-DHA at delivery that increases to 8g% during lactation. This 8g% RBC-DHA concurs with the lowest risks of cardiovascular and psychiatric diseases in adults. RBC-data from 1866 infants, males and (non-)pregnant females indicated AA vs. DHA synergism at low RBC-DHA, but antagonism at high RBC-DHA. These data, together with high intakes of AA and DHA from our Paleolithic diet, suggest that bioattenuation of DHA during pregnancy and postnatal antagonism between AA and DHA are the physiological standard for humans across the life cycle. PMID:21561751

  5. Contact sensitizers modulate the arachidonic acid metabolism of PMA-differentiated U-937 monocytic cells activated by LPS

    International Nuclear Information System (INIS)

    For the effective induction of a hapten-specific T cell immune response toward contact sensitizers, in addition to covalent-modification of skin proteins, the redox and inflammatory statuses of activated dendritic cells are crucial. The aim of this study was to better understand how sensitizers modulate an inflammatory response through cytokines production and COX metabolism cascade. To address this purpose, we used the human monocytic-like U-937 cell line differentiated by phorbol myristate acetate (PMA) and investigated the effect of 6 contact sensitizers (DNCB, PPD, hydroquinone, propyl gallate, cinnamaldehyde and eugenol) and 3 non sensitizers (lactic acid, glycerol and tween 20) on the production of pro-inflammatory cytokines (IL-1β and TNF-α) and on the arachidonic acid metabolic profile after bacterial lipopolysaccharide (LPS) stimulation. Our results showed that among the tested molecules, all sensitizers specifically prevent the production of PMA/LPS-induced COX-2 metabolites (PGE2, TxB2 and PGD2), eugenol and cinnamaldehyde inhibiting also the production of IL-1β and TNF-α. We further demonstrated that there is no unique PGE2 inhibition mechanism: while the release of arachidonic acid (AA) from membrane phospholipids does not appear do be a target of modulation, COX-2 expression and/or COX-2 enzymatic activity are the major steps of prostaglandin synthesis that are inhibited by sensitizers. Altogether these results add a new insight into the multiple biochemical effects described for sensitizers. - Highlights: → We investigated how contact sensitizers modulate an inflammatory response. → We used macrophage-differentiated cell line, U-937 treated with PMA/LPS. → Sensitizers specifically inhibit the production of COX metabolites (PGE2, TxB2). → Several mechanisms of inhibition: COX-2 expression/enzymatic activity, isomerases. → New insight in the biochemical properties of sensitizers.

  6. Effect of aspirin on the metabolism of exogenous arachidonic acid in human polymorphonuclear leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Punnonen, K.; Uotila, P.

    1984-08-01

    When human polymorphonuclear leukocytes (PMNL) were incubated with exogenous /sup 14/C-arachidonic acid (/sup 14/C-AA), both lipoxygenase and cyclo-oxygenase metabolites were detected. The amount of the 5-lipoxygenase metabolites formed, including 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), was small. The amount of other mono-HETE's (migrating in the vicinity of 12-HETE) was greater, but this was obviously mainly due to the small amount of contaminating platelets. In the presence of calcium ionophore A23187 the rate of formation of 5-HETE was increased, but the formation of other metabolites remained unchanged. When PMNL were incubated with aspirin in the presence of A23187 the formation of the cyclo-oxygenase products was decreased but that of 5-HETE was unchanged. The present study indicates that the calcium ionophore A23187 stimulates specifically the 5-lipoxygenase in human PMNL and that aspirin has no effect on the formation of the 5-lipoxygenase metabolites of arachidonic acid in human PMNL.

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

    International Nuclear Information System (INIS)

    14C-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. Regulation of the arachidonic acid-stimulated respiratory burst in neutrophils by intra- cellular and extracellular calcium

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The respiratory burst is an important physiological function ofthe neutrophils in killing the bacteria invading in human body. We used chemiluminescence method to measure the exogenous arachidonic acid-stimulated respiratory burst, and measured the cytosolic free calcium concentration in neutrophils by the fluorescence method. It was found that, on one hand, the arachidonic acid-stimulated respiratory burst was enhanced by elevating the cytosolic free calcium concentration in neutrophils with a potent endomembrane Ca2+-ATPase inhibitor, Thapsgargin; on the other hand, chelating the intracellular or extracellular calcium by EGTA or BAPTA inhibited the respiratory burst. Results showed that calcium plays an important regulatory role in the signaling pathway involved in the exogenous arachidonic acid-stimulated respiratory burst of neutrophils.

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

    International Nuclear Information System (INIS)

    The fate of exogenous 14C-arachidonic acid (14C-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 14C-AA was infused into the pulmonary circulation most of the infused 14C-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 14C-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 14C-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 14C-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

  10. Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line

    International Nuclear Information System (INIS)

    Platelet-activating factor is a potent mediator of the inflammatory response. Studies of the actions of platelet-activating factor have centered mainly around neutrophils, monocytes, and platelets. In this report we begin to uncover the influence of platelet-activating factor on B lymphocytes. Employing the EBV-transformed human B cell line SKW6.4, we demonstrate that platelet-activating factor significantly alters membrane phospholipid metabolism indicated by the incorporation of 32P into phosphatidylcholine, phosphatidylinositol, and phosphatidic acid but not significantly into phosphatidylethanolamine at concentrations ranging from 10(-9) to 10(-6) M. The inactive precursor, lyso-platelet-activating factor, at a concentration as high as 10(-7) M had no effect on any of the membrane phospholipids. We also show that platelet-activating factor from 10(-12) to 10(-6) M induced rapid and significant elevation in intracellular calcium levels, whereas lyso-platelet-activating factor was again ineffective. We further demonstrate the impact of platelet-activating factor binding to B cells by measuring platelet-activating factor induced arachidonic acid release and 5-hydroxyeicosatetraenoic acid production. Moreover, platelet-activating factor was capable of inducing transcription of the nuclear proto-oncogenes c-fos and c-jun. Finally we explored the possible role of 5-hydroxyeicosatetraenoic acid as a regulator of arachidonic acid liberation demonstrating that endogenous 5-lipoxygenase activity modulates platelet-activating factor induced arachidonic acid release perhaps acting at the level of phospholipase A2. In summary, platelet-activating factor is shown here to have a direct and profound effect on a pure B cell line

  11. 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

  12. Absorption and lymphatic transport of exogenous and endogenous arachidonic and linoleic acid in the rat

    International Nuclear Information System (INIS)

    [3H]Arachidonic (20:4) and [14C]linoleic acid (18:2) were fed to thoracic duct-cannulated rats in test meals of either tracers alone, cream, Intralipid, pure arachidonic acid, or pure linoleic acid. Less [3H]20:4 than [14C]18:2 was recovered in chyle during the first 5 h. After cream feeding, the proportion of radioactivity found in phospholipids was high and increased during the first 3 h. After the meal 61 +/- 6% of the 3H and 57 +/- 10% of the 14C was in phosphatidylcholine, and 11 +/- 3% of the 3H and 3.0 +/- 4% of the 14C was in phosphatidylethanolamine. Changing the fat vehicle to Intralipid or pure 18:2 decreased the proportion of label in the phospholipds and increased the 3H and 14C radioactivity in the triacylglycerol fraction, the distribution of 14C radioactivity in the triacylglycerol fraction, the distribution of 14C being influenced more than that of 3H. After feeding the tracers in 200 μl of pure 20:4, >90% of both isotopes was in triacylglycerol. During fasting, triacylglycerol transported 56% (0.7 μmol/h), phosphatidylethanolamine transported 10% (0.1 μmol/h) of the 20:4 mass. After cream or Intralipid feeding, the output of 20:4-containing phosphatidylcholine and phosphatidylethanolamine increased 2.1- to 2.8-fold, whereas the transport of 20:4 with triacylglycerol remained constant. Phospholipids thus became the predominant transport form for 20:4. After feeding 200 μl of 20:4, the intestine produced, however, 20:4-rich triacylglycerols that transported 80% of the chyle 20:4

  13. 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...... dose dependently (EC50 = 86 nM) stimulated depolarization-evoked exocytosis by 450% without affecting the whole cell Ca2+ current or cytoplasmic Ca2+ levels. The stimulatory effect involved priming of secretory granules as reflected by an increase in the size of the readily releasable pool of granules...

  14. 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...... (EC50 = 86 nM) stimulated depolarization-evoked exocytosis by 450% without affecting the whole cell Ca2+ current or cytoplasmic Ca2+ levels. The stimulatory effect involved priming of secretory granules as reflected by an increase in the size of the readily releasable pool of granules from 70...

  15. Roles for nitric oxide and arachidonic acid in the induction of heterosynaptic cerebellar LTD.

    Science.gov (United States)

    Reynolds, T; Hartell, N A

    2001-01-22

    In cerebellar slices conjunctive pairing of parallel fibre (PF) stimulation with depolarization of Purkinje cells (PCs) induces a long-term depression (LTD) of PF synaptic transmission that spreads to unpaired PF inputs to the same cell. Inhibitors of NO synthase (7-nitro-indazole), soluble guanylate cyclase (ODQ) and PKG (KT5823) all prevented depression at each of two independent PF pathways to a single PC. Inhibition of NOS also unmasked a platelet activating factor (PAF)-mediated synaptic potentiation of possible presynaptic origin. LTD was also prevented by the phospholipase A2 inhibitor OBAA but was rescued by co-perfusion with arachidonic acid. We conclude that NO and diffusible products of phospholipase A2 metabolism are potential mediators of the spread of cerebellar plasticity at the single cell level. PMID:11201073

  16. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

    Directory of Open Access Journals (Sweden)

    Carlos Rodrigo Camara-Lemarroy

    2012-01-01

    Full Text Available After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD. This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise.

  17. Time-dependent changes in the brain arachidonic acid cascade during cuprizone-induced demyelination and remyelination

    OpenAIRE

    Palumbo, S.; Toscano, C.D.; Parente, L.; Weigert, R.; Bosetti, F.

    2011-01-01

    Phospholipases A2 (PLA2) are the enzymatic keys for the activation of the arachidonic acid (AA) cascade and the subsequent synthesis of proinflammatory prostanoids (prostaglandins and tromboxanes). Prostanoids play critical roles in the initiation and modulation of inflammation and their levels have been reported increased in several neurological and neurodegenerative disorders, including multiple sclerosis (MS).

  18. Calcium-dependent phospholipid catabolism and arachidonic acid mobilization in cerebral minces

    International Nuclear Information System (INIS)

    Cerebral minces were used to investigate the role of calcium influx on trauma-induced alterations of brain lipid metabolism. Cerebral phospholipids, nonpolar lipids, and free fatty acids were radiolabeled in vivo with [3H]arachidonic acid. Tissue incubation stimulated the time-dependent catabolism of choline and inositol glycerophospholipids, and resulted in the accumulation of [3H]free fatty acids. These effects were attenuated in Ca2+-free incubations, and when EGTA or verapamil were present. The inhibition of calcium influx also reduced the labeling of diglycerides, whereas ethanolamine and serine glycerophospholipids were not affected by incubation or treatments. Replacing Ca2+ with other cations also attenuated the incubation-dependent alterations in lipid metabolism. However, only cadmium was able to compete with calcium and reduce the accumulation of [3H]free fatty acids. It appeared that about half of the observed phospholipid catabolism was dependent on Ca2+ influx and that at least 80% of the [3H]free fatty acid accumulation required calcium

  19. Arachidonate metabolism in bovine gallbladder muscle

    International Nuclear Information System (INIS)

    Incubation of (1-14C]arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of [1-14C]PGH2 was virtually identical to that of [1-14C]AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid

  20. Role of arachidonic acid in hyposmotic membrane stretch-induced increase in calcium-activated potassium currents in gastric myocytes

    Institute of Scientific and Technical Information of China (English)

    Meng YANG; Wen-xie XU; Xing-lan LI; Hui-ying XU; Jia-bin SUN; Bin MEI; Hai-feng ZHENG; Lian-hua PIAO; De-gang XING; Zhai-liu LI

    2005-01-01

    Aim: To study effects of arachidonic acid (AA) and its metabolites on the hyposmotic membrane stretch-induced increase in calcium-activated potassium currents (IKCa) in gastric myocytes. Methods: Membrane currents were recorded by using a conventional whole cell patch-clamp technique in gastric myocytes isolated with collagenase. Results: Hyposmotic membrane stretch and AA increased both IK(Ca) and spontaneous transient outward currents significantly.Exogenous AA could potentiate the hyposmotic membrane stretch-induced increase in IK(Ca). The hyposmotic membrane stretch-induced increase in IK(Ca) was significantly suppressed by dimethyleicosadienoic acid (100 μmol/L in pipette solution), an inhibitor of phospholipase A2. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly suppressed AA and hyposmotic membrane stretch-induced increases in IK(Ca). External calcium-free or gadolinium chloride, a blocker of stretch-activated channels, blocked the AA-induced increase in IK(Ca) significantly, but it was not blocked by nicardipine, an L-type calcium channel blocker. Ryanodine, a calcium-induced calcium release agonist, completely blocked the AA-induced increase in IK(Ca); however, heparin, a potent inhibitor of inositol triphosphate receptor, did not block the AA-induced increase in IK(Ca). Conclusion:Hyposmotic membrane stretch may activate phospholipase A2, which hydrolyzes membrane phospholipids to ultimately produce AA; AA as a second messenger mediates Ca2+ influx, which triggers Ca2+-induced Ca2+ release and elicits activation of IK(Ca) in gastric antral circular myocytes of the guinea pig.

  1. Dietary arachidonic acid and docosahexaenoic acid regulate liver fatty acid desaturase (FADS) alternative transcript expression in suckling piglets.

    Science.gov (United States)

    Wijendran, Vasuki; Downs, Ian; Srigley, Cynthia Tyburczy; Kothapalli, Kumar S D; Park, Woo Jung; Blank, Bryant S; Zimmer, J Paul; Butt, C M; Salem, Norman; Brenna, J Thomas

    2013-10-01

    Molecular regulation of fatty acid desaturase (Fads) gene expression by dietary arachidonic acid (ARA) and docosahexaenoic acid (DHA) during early post-natal period, when the demand for long chain polyunsaturated fatty acids (LC-PUFA) is very high, has not been well defined. The objective of the current study was to determine regulation of liver Fads1, Fads2 and Fads3 classical (CS) and alternative transcripts (AT) expression by dietary ARA and DHA, within the physiological range present in human breast milk, in suckling piglets. Piglets were fed one of six milk replacer formula diets (formula-reared groups, FR) with varying ARA and DHA content from days 3-28 of age. The ARA/DHA levels of the six formula diets were as follows (% total fatty acid, FA/FA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D2) 0.67/0.62; and (D1) 0.66/0.33. The control maternal-reared (MR) group remained with the dam. Fads1 expression was not significantly different between FR and MR groups. Fads2 expression was down-regulated significantly in diets with 1:1 ratio of ARA:DHA, compared to MR. Fads2 AT1 expression was highly correlated to Fads2 expression. Fads3 AT7 was the only Fads3 transcript sensitive to dietary LC-PUFA intake and was up-regulated in the formula diets with lowest ARA and DHA contents compared to MR. Thus, the present study provides evidence that the proportion of dietary ARA:DHA is a significant determinant of Fads2 expression and LC-PUFA metabolism during the early postnatal period. Further, the data suggest that Fads3 AT7 may have functional significance when dietary supply of ARA and DHA are low during early development. PMID:24075244

  2. Age-related changes in retinoic, docosahexaenoic and arachidonic acid modulation in nuclear lipid metabolism.

    Science.gov (United States)

    Gaveglio, Virginia L; Pascual, Ana C; Giusto, Norma M; Pasquaré, Susana J

    2016-08-15

    The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity. Interestingly, RA, DHA and AA were observed to modulate these enzymatic activities and this modulation was found to change in aged rats. In adult nuclei, whereas RA led to high DAG and MAG production through inhibition of their hydrolytic enzymes, DHA and AA promoted high MAG production by LPAPase and DAGL stimulation. In contrast, in aged nuclei RA caused high MAG generation whereas DHA and AA diminished it through LPAPase activity modulation. These results demonstrate that aging promotes a different nuclear lipid metabolism as well as a different type of non-genomic regulation by RA, DHA and AA, which could be involved in nuclear signaling events. PMID:27355428

  3. Effects of arachidonic acid on ATP-sensitive K+ current in murine colonic smooth muscle cells.

    Science.gov (United States)

    Jun, Jae Yeoul; Yeum, Cheol Ho; Park, Yoo Whan; Jang, In Youb; Kong, In Deok; Sim, Jae Hoon; So, Insuk; Kim, Ki Whan; You, Ho Jin

    2002-09-01

    The effects of arachidonic acid (AA) and the mechanism through which it modulates ATP-sensitive K+ (K(ATP)) currents were examined in single smooth muscle cells of murine proximal colon. In the current-clamping mode, AA and glibenclamide induced depolarization of membrane potential. Using 0.1 mM ATP and 140 mM K+ solution in the pipette and 90 mM K+ in the bath solution at a -80 mV of holding potential, pinacidil activated the glibenclamide-sensitive inward current. The potential of these currents was reversed to near the equilibrium potential of K+ by 60 mM K+ in the bath solution. AA inhibited K(ATP) currents in a dose-dependent manner. This inhibition was not changed when 1 mM GDPbetaS was present in the pipette. Chelerythrine, protein kinase C inhibitor, did not block the AA effects. Superoxide dismutase and metabolic inhibitors (indomethacin and nordihydroguaiacretic acid) of AA did not affect the AA-induced inhibition. Eicosatetraynoic acid, a nonmetabolizable analogue of AA, inhibited the K(ATP) currents. These results suggest that AA-induced inhibition of K(ATP) currents is not mediated by G-protein or protein kinase C activation. The inhibitory action is likely to be a possible mechanism of AA-induced membrane depolarization. PMID:12396031

  4. Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis.

    Science.gov (United States)

    Hyde, C A C; Missailidis, S

    2009-06-01

    Arachidonic acid (AA) and its metabolites have recently generated a heightened interest due to growing evidence of their significant role in cancer biology. Thus, inhibitors of the AA cascade, first and foremost COX inhibitors, which have originally been of interest in the treatment of inflammatory conditions and certain types of cardiovascular disease, are now attracting attention as an arsenal against cancer. An increasing number of investigations support their role in cancer chemoprevention, although the precise molecular mechanisms that link levels of AA, and its metabolites, with cancer progression have still to be elucidated. This article provides an overview of the AA cascade and focuses on the roles of its inhibitors and their implication in cancer treatment. In particular, emphasis is placed on the inhibition of cell proliferation and neo-angiogenesis through inhibition of the enzymes COX-2, 5-LOX and CYP450. Downstream effects of inhibition of AA metabolites are analysed and the molecular mechanisms of action of a selected number of inhibitors of catalytic pathways reviewed. Lastly, the benefits of dietary omega-3 fatty acids and their mechanisms of action leading to reduced cancer risk and impeded cancer cell growth are mentioned. Finally, a proposal is put forward, suggesting a novel and integrated approach in viewing the molecular mechanisms and complex interactions responsible for the involvement of AA metabolites in carcinogenesis and the protective effects of omega-3 fatty acids in inflammation and tumour prevention. PMID:19239926

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

    Energy Technology Data Exchange (ETDEWEB)

    Uotila, P.; Puustinen, T.

    1985-06-01

    The fate of exogenous /sup 14/C-arachidonic acid (/sup 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 /sup 14/C-AA was infused into the pulmonary circulation most of the infused /sup 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 /sup 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 /sup 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 /sup 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.

  6. 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

    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...... 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...

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

    International Nuclear Information System (INIS)

    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 [14C]-AA and [14C]-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 A4 and leukotriene A5 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

  8. Breeding of arachidonic acid-producing strain by low-energy ion implantation

    International Nuclear Information System (INIS)

    Low energy ion implantation technology was used in mutation breeding on arachidonic acid (5, 8, 11, 14-eicosatetraenoic acid, AA) yielding starting strain, Mortierelle alpina N7. The results indicate that dispersion of descendants of the N7 strain implanted with 10 keV N+ (3 x 1014 N+/cm2) was bigger than that in natural division strain. I49-N18, a high-yield AA-producing strain, was screened out by continuous mutagenicity. The biomass, lipid in biomass, AA in lipids of the high-yield strain were 26.3 g/L, 33.8%(w/w), and 52.36%(w/w), respectively. The AA content in culture was 4.66 g/L, which is 126.2% higher than the control, and its descendiblity was stable. It is concluded that I49-N18 is a promising strain for industrialization, and that ion implantation has remarkable mutagenic effect on microorganism

  9. Culture media optimization of Porphyridium purpureum: production potential of biomass, total lipids, arachidonic and eicosapentaenoic acid.

    Science.gov (United States)

    Kavitha, Mysore Doddaiah; Kathiresan, Shanmugam; Bhattacharya, Sila; Sarada, Ravi

    2016-05-01

    Porphyridium purpureum a red marine microalga is known for phycobiliproteins (PB), polyunsaturated fatty acids and sulphated exopolysaccharides. In the present study, effects of media constituents for the production of different polyunsaturated fatty acids from P. purpureum were considered using a response surface methodology (RSM). A second order polynomial was used to predict the response functions in terms of the independent variables such as the concentrations of sodium chloride, magnesium sulphate, sodium nitrate and potassium dihydrogen phosphate. The response functions were production of biomass yield, total lipid and polyunsaturated fatty acids like arachidonic acid (AA 20:4) and eicosapentaenoic acid (EPA 20:5). Results corroborated that maximum Biomass (0.95 gL(-1)) yield was at the concentrations of sodium chloride (14.89 gL(-1)), magnesium sulfate (3.93 gL(-1)) and sodium nitrate (0.96 gL(-1)) and potassium dihydrogen phosphate (0.09 gL(-1)). Optimum total lipid (17.9 % w/w) and EPA (34.6 % w/w) content was at the concentrations of sodium chloride (29.98 gL(-1)), magnesium sulfate (9.34 gL(-1)) and sodium nitrate (1.86 gL(-1)). Variation in concentration of potassium dihydrogen phosphate for both lipid (0.01gL(-1)) and EPA content (0.20 gL(-1)) was observed. The optimum conditions for biomass, total lipid, AA and EPA varied indicating their batch mode of growth and interaction effect of the salt. PMID:27407193

  10. 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.

  11. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice.

    Science.gov (United States)

    Oliveros, L B; Videla, A M; Giménez, M S

    2004-03-01

    We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA) turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet), or the control diet containing soybean oil as fat source (10 mice per group). The fat content of each diet was 15% (w/w). Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL+VLDL)-cholesterol, thiobarbituric acid-reactive substances (TBARS) and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [3H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [3H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [3H]-AA uptake but induced an increase in [3H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress. PMID:15060696

  12. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

    Directory of Open Access Journals (Sweden)

    L.B. Oliveros

    2004-03-01

    Full Text Available We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet, or the control diet containing soybean oil as fat source (10 mice per group. The fat content of each diet was 15% (w/w. Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL + VLDL-cholesterol, thiobarbituric acid-reactive substances (TBARS and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [³H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [³H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [³H]-AA uptake but induced an increase in [³H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

  13. 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.

  14. Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects.

    Science.gov (United States)

    Altinbas, Burcin; Topuz, Bora Burak; İlhan, Tuncay; Yilmaz, Mustafa Sertac; Erdost, Hatice; Yalcin, Murat

    2014-08-01

    The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3-H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions. PMID:25065747

  15. Shuffling the cards in signal transduction: Calcium, arachidonic acid and mechanosensitivity

    Institute of Scientific and Technical Information of China (English)

    Luca; Munaron

    2011-01-01

    Cell signaling is a very complex network of biochemical reactions triggered by a huge number of stimuli coming from the external medium. The function of any single signaling component depends not only on its own structure but also on its connections with other biomolecules. During prokaryotic-eukaryotic transition, the rearrangement of cell organization in terms of diffusional compartmentalization exerts a deep change in cell signaling functional potentiality. In this review I briefly introduce an intriguing ancient relationship between pathways involved in cell responses to chemical agonists (growth factors, nutrients, hormones) as well as to mechanical forces (stretch, osmotic changes). Some biomolecules (ion channels and enzymes) act as "hubs", thanks to their ability to be directly or indirectly chemically/mechanically co-regulated. In particular calcium signaling machinery and arachidonic acid metabolism are very ancient networks, already present before eukaryotic appearance. A number of molecular "hubs", including phospholipase A2 and some calcium channels, appear tightly interconnected in a cross regulation leading to the cellular response to chemical and mechanical stimulations.

  16. The effects of anaerobic training in serum lipids and arachidonic acid metabolites

    Directory of Open Access Journals (Sweden)

    GEORGIOS KIPREOS

    2010-01-01

    Full Text Available Coronary arteries are subjected daily in high shear stress and manifest atherosclerosis very early in life in comparison to other arteries in the human body. Some factors that are implicated in the evolution and progress of this process are the concentration of lipids and arachidonic acid metabolites, such prostacyclin and thromboxane. It has been reported that those who participate in aerobic activities such as walking, cycling, jogging or brisk walking might have normal values of the mentioned chemical substances. On the other hand, it is reported that the effects of anaerobic and strength activities has negative effects on the vascular endothelium, which is essential for the maintenance of hemostatic balance and the local regulation of vascular tone.Therefore, even although extensive research has been conducted in this field, there are crucial gaps in our knowledge. Consequently, the purpose of this brief review is to describe what is known about the effects of anaerobic activities in which the competitive athletes have participated on the following blood parameters: Total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL - C, low density lipoproteins cholesterol (LDL - C, prostacyclin & thromboxane.

  17. Improving arachidonic acid fermentation by Mortierella alpina through multistage temperature and aeration rate control in bioreactor.

    Science.gov (United States)

    Gao, Min-Jie; Wang, Cheng; Zheng, Zhi-Yong; Zhu, Li; Zhan, Xiao-Bei; Lin, Chi-Chung

    2016-05-18

    Effective production of arachidonic acid (ARA) using Mortierella alpina was conducted in a 30-L airlift bioreactor. Varying the aeration rate and temperature significantly influenced cell morphology, cell growth, and ARA production, while the optimal aeration rate and temperature for cell growth and product formation were quite different. As a result, a two-stage aeration rate control strategy was constructed based on monitoring of cell morphology and ARA production under various aeration rate control levels (0.6-1.8 vvm). Using this strategy, ARA yield reached 4.7 g/L, an increase of 38.2% compared with the control (constant aeration rate control at 1.0 vvm). Dynamic temperature-control strategy was implemented based on the fermentation performance at various temperatures (13-28°C), with ARA level in total cellular lipid increased by 37.1% comparing to a constant-temperature control (25°C). On that basis, the combinatorial fermentation strategy of two-stage aeration rate control and dynamic temperature control was applied and ARA production achieved the highest level of 5.8 g/L. PMID:26038800

  18. Intestinal zinc transport: influence of streptozotocin-induced diabetes, insulin and arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Song, M.K.; Mooradian, A.D.

    1988-01-01

    The influence of arachidonic acid (AA) on the zinc flux rates of jejunal segments, isolated from streptozotocin-induced diabetic rats injected with saline or with insulin, was investigated using an Ussing chamber technique. Although the zinc flux rates from mucose-to-serosa (J/sub ms/) of normal rats were inhibited by addition of 5 ..mu..M AA to the jejunal segment bathing medium, AA had no effect on the J/sub ms/ of diabetic rats either with or without insulin treatment. Induction of diabetes also significantly reduces J/sub ms/, but 3 day insulin treatment did not reverse this effect. Addition of AA to the serosal side did not significantly alter the zinc flux rate from serosa-to-mucosa (J/sub sm/) in either control, diabetic or diabetic rats treated with insulin. The net zinc absorption rate (J/sub net/) of jejunal segments was decreased in diabetic rats compared to controls, but normalization of blood glucose with 3 day insulin treatment did not increase J/sub net/. Addition of AA was associated with a tendency to increase zinc uptake capacity. This change reached statistical significance in insulin treated diabetic rats. Short-circuit current (I/sub sc/) for diabetic rats was increased compared to controls but addition of AA to the mucosal side bathing medium decreased I/sub sc/ in all groups. 32 references, 3 figures, 1 table.

  19. Assay of phospholipase A2 with E. coli membrane doped by 3H-arachidonic acid

    International Nuclear Information System (INIS)

    Objective: To develop a new radiochemistry method to assay the secretory phospholipase A2 (sPLA2) and cytosolic phospholipase A2 (cPLA2) with a same substrate. Methods: E.coli membrane doped by 3H-arachidonic acid was prepared and hydrolyzed by PLA2 in certain condition, and the enzyme activity was expressed with the hydrolyzing rate. Results: Intra-day coefficient of variation (CV) of cPLA2 was 5.2% and inter-day CV was 10.9%, and 4.9% and 7.8% for sPLA2 respectively. Results of a series proportional dilution assay showed a good linear relationship. Serum sPLA2 activities of patients with acute cholecystitis were significantly higher than that of normal control subjects. There was a significant difference of activities of sPLA2 and cPLA2 between the endotoxin induced leukemia cell K562 and control. Conclusions: This method is specific, stable and sensitive, it may be used in clinical and scientific research

  20. The metabolism of arachidonic acid in isolated perfused fetal and neonatal rabbit lungs

    International Nuclear Information System (INIS)

    The developmental pattern of fetal and neonatal rabbit lungs to metabolize arachidonic acid (AA) to different cyclo-oxygenase products was studied in isolated rabbit lungs, which were perfused with Krebs bicarbonate buffer. 14C-AA (66 nmol) was injected into the pulmonary circulation and the nonrecirculating perfusion effluent was collected for four minutes. About ten per cent of the injected radioactivity was found in the 0-4 min perfusion effluent. The metabolites of AA in the effluent were analyzed by thin layer chromatography. The major metabolites of AA were PGE2 and its 15-keto-derivates, but also PGF2 alpha and its 15-keto-derivates, TXB2 and 6-keto-PGF1 alpha were found in the effluent. The most drastic developmental change was the increase in the amount of 15-keto-metabolites of PGE2 from late fetal period to the lungs of one day old rabbits (1.8 fold increase between birth and first postnatal day). Smaller changes were detected in the amounts of other cyclo-oxygenase products

  1. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    OpenAIRE

    Harry Gaylia; Kraft Andrew; Chen Mei; Greenstein Dede; Kellom Matthew; Kim Hyung-Wook; Rao Jagadeesh; Rapoport Stanley; Basselin Mireille

    2011-01-01

    Abstract Background Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers...

  2. Effects of chronic clozapine administration on markers of arachidonic acid cascade and synaptic integrity in rat brain

    OpenAIRE

    Kim, Hyung-Wook; Cheon, Yewon; Modi, Hiren R.; Rapoport, Stanley I; Rao, Jagadeesh S.

    2012-01-01

    The mode of action of clozapine, an atypical antipsychotic approved for treating schizophrenia and bipolar disorder (BD) mania, remains unclear. We tested for overlap with the actions of the mood stabilizers, lithium, carbamazepine and valproate, which downregulate arachidonic acid (AA) cascade markers in rat brain and upregulate BDNF. AA cascade markers are upregulated in the postmortem BD brain in association with neuroinflammation and synaptic loss, while BDNF is decreased. Rats were injec...

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

    International Nuclear Information System (INIS)

    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 14C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14C-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

  4. Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade.

    Science.gov (United States)

    Rapoport, Stanley I

    2014-06-18

    This Review evaluates the arachidonic acid (AA, 20:4n-6) cascade hypothesis for the actions of lithium and other FDA-approved mood stabilizers in bipolar disorder (BD). The hypothesis is based on evidence in unanesthetized rats that chronically administered lithium, carbamazepine, valproate, or lamotrigine each downregulated brain AA metabolism, and it is consistent with reported upregulated AA cascade markers in post-mortem BD brain. In the rats, each mood stabilizer reduced AA turnover in brain phospholipids, cyclooxygenase-2 expression, and prostaglandin E2 concentration. Lithium and carbamazepine also reduced expression of cytosolic phospholipase A2 (cPLA2) IVA, which releases AA from membrane phospholipids, whereas valproate uncompetitively inhibited in vitro acyl-CoA synthetase-4, which recycles AA into phospholipid. Topiramate and gabapentin, proven ineffective in BD, changed rat brain AA metabolism minimally. On the other hand, the atypical antipsychotics olanzapine and clozapine, which show efficacy in BD, decreased rat brain AA metabolism by reducing plasma AA availability. Each of the four approved mood stabilizers also dampened brain AA signaling during glutamatergic NMDA and dopaminergic D2 receptor activation, while lithium enhanced the signal during cholinergic muscarinic receptor activation. In BD patients, such signaling effects might normalize the neurotransmission imbalance proposed to cause disease symptoms. Additionally, the antidepressants fluoxetine and imipramine, which tend to switch BD depression to mania, each increased AA turnover and cPLA2 IVA expression in rat brain, suggesting that brain AA metabolism is higher in BD mania than depression. The AA hypothesis for mood stabilizer action is consistent with reports that low-dose aspirin reduced morbidity in patients taking lithium, and that high n-3 and/or low n-6 polyunsaturated fatty acid diets, which in rats reduce brain AA metabolism, were effective in BD and migraine patients. PMID

  5. Fatty acid transfer in the food web of a coastal Mediterranean lagoon: Evidence for high arachidonic acid retention in fish

    Science.gov (United States)

    Koussoroplis, Apostolos-Manuel; Bec, Alexandre; Perga, Marie-Elodie; Koutrakis, Emmanuil; Bourdier, Gilles; Desvilettes, Christian

    2011-02-01

    The transfer of fatty acids (FAs) in the food web of a Mediterranean lagoon was studied using FA compositional patterns across several trophic levels. The structure of the food web was inferred from C and N stable isotopes values and an isotope mixing model was used in order to estimate the relative contribution of the different potential food sources to the biomass of consumers. Bidimensional plots of FA composition of food web components against their δ 15N values indicated a general trend of increasing proportions of highly unsaturated fatty acids (HUFAs) with increasing trophic levels while the proportions of saturated fatty acids (SAFAs) and 18-carbon polyunsaturated fatty acids (PUFAs) decreased. Using the relative contributions of food sources to consumers and their FA compositions, a model was built in order to estimate the PUFA composition of consumer mixed diets which was compared to consumer PUFA profiles. The latter allowed the identification of the PUFAs which were mostly enriched/retained in consumer lipids. There was a surprisingly high retention of arachidonic acid (ARA), a trend which challenges the idea of low ARA needs in marine fish and suggests the important physiological role of this essential FA for fish in estuarine environments.

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

    International Nuclear Information System (INIS)

    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

  7. Eugenol: a dual inhibitor of platelet-activating factor and arachidonic acid metabolism.

    Science.gov (United States)

    Saeed, S A; Simjee, R U; Shamim, G; Gilani, A H

    1995-07-01

    Eugenol is an active principal and responsible for several pharmacological activities of clove oil. We studied the effects of eugenol on human platelet aggregation, arachidonic acid (AA) and platelet-activating factor (PAF) metabolism and in vivo effects on AA and PAF-induced shock in rabbits. Eugenol strongly inhibited PAF-induced platelet aggregation with lesser effect against AA and collegen. The IC(50) values were against AA: 31 ± 0.5; collagen: 64 ± 0.7 and PAF 7 ± 0.2 μM (n=9) respectively. In addition, eugenol stimulated PAF-acetylhydrolase activity suggesting that inhibition of PAF could be due to its inactivation to lyso-PAF. Pretreatment of rabbits with eugenol (50-100 mg/kg) prevented the lethal effects of intravenous PAF (11 μgg/kg) or AA (2 mg/kg) in a dose-dependent fashion. The protective effects of eugenol in the rabbits, however, were more pronounced against PAF-induced mortality (100% protection). In addition, eugenol also inhibited AA metabolism via cyclooxygenase and lipoxygenase pathways in human platelets. Both the production of thromboxane-A(2) and 12-hydroxy-eicosatetraenoic acid was inhibited by eugenol in a concentration-related manner (30-120 μM). In vivo, eugenol (50-100 mg/kg; i.p.) inhibited carrageenan-induced rat paw oedema (P < 0.001). In this test, eugenol was 5 times more potent than aspirin. These results provide evidence that eugenol acts as a dual antagonist of AA and PAF. PMID:23196096

  8. Influence of dietary linoleic acid intake with different fat intakes on arachidonic acid concentrations in plasma and platelet lipids and eicosanoid biosynthesis in female volunteers

    OpenAIRE

    Adam, Olaf; Wolfram, G.; Zöllner, N.

    2003-01-01

    Background/Aim: N-6 fatty acids are considered to promote diseases prevalent in industrialized countries and characterized by an increased eicosanoid biosynthesis from arachidonic acid (AA). We investigated the impact of the linoleic acid (LA) intake on AA levels in humans. Methods: Six healthy female volunteers (age range 2334 years) were given liquid formula diets (LFD) devoid of AA for 6 weeks, providing a constant intake of zero energy% (LFD 0: protein 15%, carbohydrates 85%) or 20 energy...

  9. Arachidonic acid pathway activates multidrug resistance related protein in cultured human lung cells.

    Science.gov (United States)

    Torky, Abdelrahman; Raemisch, Anja; Glahn, Felix; Foth, Heidi

    2008-05-01

    Primary cultures of human lung cells can serve as a model system to study the mechanisms underlying the effects of irritants in air and to get a deeper insight into the (patho)physiological roles of the xenobiotic detoxification systems. For 99 human lung cancer cases the culture duration for bronchial epithelium and peripheral lung cells (PLC) are given in term of generations and weeks. Using this system, we investigated whether and how prostaglandins (PG) modify multidrug resistance related protein (MRP) function in normal human lung cells. PGF2alpha had no effect on MRP function, whereas PGE2 induced MRP activity in cultured NHBECs. The transport activity study of MRP in NHBEC, PLC, and A549 under the effect of exogenously supplied PGF2alpha (10 microM, 1 day) using single cell fluorimetry revealed no alteration in transport activity of MRP. PG concentrations were within the physiological range. COX I and II inhibitors indomethacin (5, 10 microM) and celecoxib (5, 10 microM) could substantially decrease the transport activity of MRP in NHBEC, PLC, and A549 in 1- and 4-day trials. Prostaglandin E2 did not change cadmium-induced caspase 3/7 activation in NHBECs and had no own effect on caspase 3/7 activity. Cadmium chloride (5, 10 microM) was an effective inducer of caspase 3/7 activation in NHBECs with a fivefold and ninefold rise of activity. In primary human lung cells arachidonic acid activates MRP transport function only in primary epithelial lung cells by prostaglandin E2 but not by F2alpha mediated pathways and this effect needs some time to develop. PMID:17943274

  10. LC/ESI-MS/MS method for determination of salivary eicosapentaenoic acid concentration to arachidonic acid concentration ratio.

    Science.gov (United States)

    Ogawa, Shoujiro; Tomaru, Koki; Matsumoto, Nagisa; Watanabe, Shui; Higashi, Tatsuya

    2016-01-01

    A simple liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) method for determination of the eicosapentaenoic acid (EPA) concentration to arachidonic acid (AA) concentration ratio in human saliva has been developed. The EPA/AA ratio in serum or plasma is widely recognized as a useful indicator in identifying the risk of cardiovascular disease, especially atherosclerosis. The salivary EPA/AA ratio is expected to be a convenient alternative to the serum or plasma EPA/AA ratio, because saliva offers the advantages of easy and noninvasive sampling. The saliva was deproteinized with acetonitrile, purified using an Oasis HLB cartridge, and derivatized with 1-[(4-dimethylaminophenyl)carbonyl]piperazine (DAPPZ). The derivatized EPA and AA were subjected to LC/ESI-MS/MS, and the EPA/AA ratio was determined using the selected reaction monitoring mode. The DAPPZ-derivatization increased the ESI sensitivity by 100- and 300-fold for EPA and AA, respectively, and enabled the detection of trace fatty acids in saliva using a 200 μL sample. The assay reproducibility was satisfactory (relative standard deviation, <5.0%). The method was successfully applied to the measurement of the salivary EPA/AA ratios of healthy Japanese subjects and their changes owing to the supplementation of EPA. PMID:25620210

  11. 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...

  12. Anti-Inflammation Effects and Potential Mechanism of Saikosaponins by Regulating Nicotinate and Nicotinamide Metabolism and Arachidonic Acid Metabolism.

    Science.gov (United States)

    Ma, Yu; Bao, Yongrui; Wang, Shuai; Li, Tianjiao; Chang, Xin; Yang, Guanlin; Meng, Xiansheng

    2016-08-01

    Inflammation is an important immune response; however, excessive inflammation causes severe tissue damages and secondary inflammatory injuries. The long-term and ongoing uses of routinely used drugs such as non-steroidal anti-inflammatory drugs (NSAIDS) are associated with serious adverse reactions, and not all patients have a well response to them. Consequently, therapeutic products with more safer and less adverse reaction are constantly being sought. Radix Bupleuri, a well-known traditional Chinese medicine (TCM), has been reported to have anti-inflammatory effects. However, saikosaponins (SS) as the main pharmacodynamic active ingredient, their pharmacological effects and action mechanism in anti-inflammation have not been reported frequently. This study aimed to explore the anti-inflammatory activity of SS and clarify the potential mechanism in acute inflammatory mice induced by subcutaneous injection of formalin in hind paws. Paw edema was detected as an index to evaluate the anti-inflammatory efficacy of SS. Then, a metabolomic method was used to investigate the changed metabolites and potential mechanism of SS. Metabolite profiling was performed by high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). The detection and identification of the changed metabolites were systematically analyzed by multivariate data and pathway analysis. As a result, 12 different potential biomarkers associated with SS in anti-inflammation were identified, including nicotinate, niacinamide, arachidonic acid (AA), and 20-carboxy-leukotriene B4, which are associated with nicotinate and nicotinamide metabolism and arachidonic acid metabolism. The expression levels of biomarkers were effectively modulated towards the normal range by SS. It indicated that SS show their effective anti-inflammatory effects through regulating nicotinate and nicotinamide metabolism and arachidonic acid metabolism. PMID:27251379

  13. The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system

    Directory of Open Access Journals (Sweden)

    Sarkadi-Nagy Eszter A

    2005-06-01

    Full Text Available Abstract Background Docosahexaenoic acid (DHA and arachidonic acid (ARA are major components of the cerebral cortex and visual system, where they play a critical role in neural development. We quantitatively mapped fatty acids in 26 regions of the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA and ARA supplementation and prematurity on CNS DHA and ARA concentrations. Methods Baboons were randomized into a breastfed (B and four formula-fed groups: term, no DHA/ARA (T-; term, DHA/ARA supplemented (T+; preterm, no DHA/ARA (P-; preterm and DHA/ARA supplemented (P+. At four weeks adjusted age, brains were dissected and total fatty acids analyzed by gas chromatography and mass spectrometry. Results DHA and ARA are rich in many more structures than previously reported. They are most concentrated in structures local to the brain stem and diencephalon, particularly the basal ganglia, limbic regions, thalamus and midbrain, and comparatively lower in white matter. Dietary supplementation increased DHA in all structures but had little influence on ARA concentrations. Supplementation restored DHA concentrations to levels of breastfed neonates in all regions except the cerebral cortex and cerebellum. Prematurity per se did not exert a strong influence on DHA or ARA concentrations. Conclusion 1 DHA and ARA are found in high concentration throughout the primate CNS, particularly in gray matter such as basal ganglia; 2 DHA concentrations drop across most CNS structures in neonates consuming formulas with no DHA, but ARA levels are relatively immune to ARA in the diet; 3 supplementation of infant formula is effective at restoring DHA concentration in structures other than the cerebral cortex. These results will be useful as a guide to future investigations of CNS function in the absence of dietary DHA and ARA.

  14. 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

  15. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

    OpenAIRE

    Oliveros L.B.; Videla A.M.; Giménez M.S.

    2004-01-01

    We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA) turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet), or the control diet containing soybean oil as fat source (10 mice per group). The fat content of each diet was 15% (w/w). Mice were fed for 6 weeks and then sacr...

  16. Altered Arachidonic Acid Cascade Enzymes in Postmortem Brain from Bipolar Disorder Patients

    OpenAIRE

    Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.

    2009-01-01

    Mood stabilizers that are approved for treating bipolar disorder (BD), when given chronically to rats, decrease expression of markers of the brain arachidonic metabolic cascade, and reduce excitotoxicity and neuroinflammation-induced upregulation of these markers. These observations, plus evidence for neuroinflammation and excitotoxicity in BD, suggest that AA cascade markers are upregulated in the BD brain. To test this hypothesis, these markers were measured in postmortem frontal cortex fro...

  17. Lyso(bis)phosphatidic acid: a preferred donor of arachidonic acid for macrophage-synthesis of eicosanoids

    International Nuclear Information System (INIS)

    In order to dissect mechanisms of arachidonic acid (20:4) metabolism, two cell populations were investigated, resident (AM) and Bacillus Calmette-Guerin-activated (BCG-AM) rabbit alveolar macrophages. After purified AM were labeled overnight with [3H]20:4, radioactivity was localized primarily within lyso(bis)phosphatidic acid [L(bis)PA] (13.1%), phosphatidylethanolamine (PE) (22.8%) and phosphatidylcholine (PC) (26.7%), with lesser amounts recovered in phosphatidyl-serine (PS) plus phosphatidylinositol (PI) (9.2%). By contrast, analysis of the phospholipid classes from prelabeled BCG-AM revealed that the mass of L(bis)PA as well as its [3H]20:4 content was profoundly decreased while other BCG-AM phospholipids remained unchanged. When [3H]20:4-labeled AM were stimulated with 1 μM 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a loss of [3H]20:4 was observed from L(bis)PA, PE, PC, and PS/PI with a corresponding increase in eicosanoid synthesis. BCG-AM exposed to either TPA or 3.8 μM Ca+2 ionophore A23187 liberated [3H]20:4 solely from Pe and PC. BCG-AM, which exhibited depressed eicosanoid formation, consistently failed to deacylate [3H]20:4 from L(bis)PA or PI. Their evidence suggests that the diminution of eicosanoid synthesis by BCG-AM may be due to the reduction of 20:4 contained within specific phospholipid pools, namely L(bis)PA

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-08-01

    /sup 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.

  19. Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle

    OpenAIRE

    1992-01-01

    The effects of arachidonic acid (AA) and other long-chain fatty acids on voltage-dependent Ca channel current (ICa) were investigated, with the whole cell patch clamp method, in longitudinal smooth muscle cells of rabbit ileum. 10-30 microM AA caused a gradual depression of ICa. The inhibitory effect of AA was not prevented by indomethacin (10 microM) (an inhibitor of cyclooxygenase) or nordihydroguaiaretic acid (10 microM) (an inhibitor of lipoxygenase). 1-(5-Isoquinolinesulfonyl)- 2-methylp...

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-05-01

    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.

  2. Attachment of fatty acid substrate fragments to prostaglandin (PG) H synthase during reaction with arachidonate

    International Nuclear Information System (INIS)

    Pure ovine synthase was incubated aerobically with 14C-arachidonate to inactivate the cyclooxygenase. After solvent extraction to remove the bulk of the lipid, the inactive protein was analyzed by polyacrylamide gel electrophoresis. In SDS-PAGE radioactive label was associated with protein that comigrated with the 70 K Da synthase subunit, as well as with protein that accumulated at the upper edge of the resolving gel. In HPLC radioactivity was found in two peaks eluting in the region of unreacted synthase. SDS-PAGE analysis of pooled material from these HPLC peaks gave a distribution of radioactivity similar to that obtained with the unfractionated material. The radioactivity and protein content of inactivated synthase purified by HPLC indicated that 0.3-1.0 mole of substrate fragment were bound per mole of synthase subunit. Incubation of a mixture of the synthase and ovalbumin with arachidonate resulted in 5-fold more labelling of synthase than ovalbumin. Thus, a substrate fragment appears to become selectively attached to the synthase during reaction, and may represent the product of a self-inactivation event

  3. 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)

    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 [1-14C]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

  4. Heating of vegetable oils influences the activity of enzymes participating in arachidonic acid formation in Wistar rats.

    Science.gov (United States)

    Stawarska, Agnieszka; Białek, Agnieszka; Tokarz, Andrzej

    2015-10-01

    Dietary intake of lipids and their fatty acids profile influence many aspects of health. Thermal processing changes the properties of edible oils and can also modify their metabolism, for example, eicosanoids formation. The aim of our study was to verify whether the activity of desaturases can be modified by lipids intake, especially by the fatty acids content. The experimental diets contained rapeseed oil, sunflower oil, and olive oil, both unheated and heated (for 10 minutes at 200 °C each time before administration), and influenced the fatty acids composition in serum and the activity of enzymes participating in arachidonic acid (AA) formation. The activity of desaturases was determined by measuring the amounts of AA formed in vitro derived from linoleic acid as determined in liver microsomes of Wistar rats. In addition, the indices of ∆(6)-desaturase (D6D) and ∆(5)-desaturase (D5D) have been determined. To realize this aim, the method of high-performance liquid chromatography has been used with ultraviolet-visible spectrophotometry detection. Diet supplementation with the oils rich in polyunsaturated fatty acids affects the fatty acids profile in blood serum and the activity of D6D and ∆(5)-desaturase in rat liver microsomes, the above activities being dependent on the kind of oil applied. Diet supplementation with heated oils has been found to increase the amount of AA produced in hepatic microsomes; and in the case of rapeseed oil and sunflower oil, it has also increased D6D activity. PMID:26094213

  5. Discovery of Novel 15-Lipoxygenase Activators To Shift the Human Arachidonic Acid Metabolic Network toward Inflammation Resolution.

    Science.gov (United States)

    Meng, Hu; McClendon, Christopher L; Dai, Ziwei; Li, Kenan; Zhang, Xiaoling; He, Shan; Shang, Erchang; Liu, Ying; Lai, Luhua

    2016-05-12

    For disease network intervention, up-regulating enzyme activities is equally as important as down-regulating activities. However, the design of enzyme activators presents a challenging route for drug discovery. Previous studies have suggested that activating 15-lipoxygenase (15-LOX) is a promising strategy to intervene the arachidonic acid (AA) metabolite network and control inflammation. To prove this concept, we used a computational approach to discover a previously unknown allosteric site on 15-LOX. Both allosteric inhibitors and novel activators were discovered using this site. The influence of activating 15-LOX on the AA metabolite network was then investigated experimentally. The activator was found to increase levels of 15-LOX products and reduce production of pro-inflammatory mediators in human whole blood assays. These results demonstrate the promising therapeutic value of enzyme activators and aid in further development of activators of other proteins. PMID:26290290

  6. 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

  7. 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

  8. Nonenzymatic pathway of PUFA oxidation. A first-principles study of the reactions of OH radical with 1,4-pentadiene and arachidonic acid

    Czech Academy of Sciences Publication Activity Database

    Szöri, Milan; Csizmadia, I. G.; Viskolcz, B.

    2008-01-01

    Roč. 4, č. 9 (2008), s. 1472-1479. ISSN 1549-9618 Institutional research plan: CEZ:AV0Z40550506 Keywords : OH radical * arachidonic acid * ab initio * nonenzymatic biosynthesis Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.274, year: 2008

  9. 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

    2005-01-01

    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

  10. Lipoxygenase- and cyclooxygenase-reaction products and incorporation into glycerolipids or radiolabeled arachidonic acid in the bovine retina

    International Nuclear Information System (INIS)

    The metabolism of radiolabeled arachidonic acid (AA) by the intact bovine retina in vitro has been studied. Synthesis of prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs), and incorporation of AA into glycerolipids has been measured by reverse-phase and straight-phase high performance liquid chromatography with flow scintillation detection, and by thin-layer chromatography. AA was actively acylated into glycerolipids, particularly triglycerides, phosphatidylcholine and phosphatidylinositol. AA was also converted to the major PGs, PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha and TXB2, and to the lipoxygenase reaction products, 12-HETE, 5-HETE, and other monohydroxy isomers. Approximately 6% of the radiolabeled AA was converted to eicosanoids. The synthesis of HETEs was inhibited in a concentration-dependent manner (IC50 . 8.3 nM) by nordihydroguaiaretic acid (NDGA). PG synthesis was inhibited by aspirin (10 microM), indomethacin (1 microM) and NDGA (IC50 . 380 nM). Metabolism of AA via lipoxygenase, cyclooxygenase and activation-acylation was inhibited by boiling retinal tissue prior to incubation. These studies demonstrate an active system for the uptake and utilization of AA in the bovine retina, and provide the first evidence of lipoxygenase-mediated metabolism of AA, resulting in the synthesis of mono-hydroxyeicosatetraenoic acids, in the retina

  11. Generation of Bioactive Oxylipins from Exogenously Added Arachidonic, Eicosapentaenoic and Docosahexaenoic Acid in Primary Human Brain Microvessel Endothelial Cells.

    Science.gov (United States)

    Aukema, Harold M; Winter, Tanja; Ravandi, Amir; Dalvi, Siddhartha; Miller, Donald W; Hatch, Grant M

    2016-05-01

    The human blood-brain barrier (BBB) is the restrictive barrier between the brain parenchyma and the circulating blood and is formed in part by microvessel endothelial cells. The brain contains significant amounts of arachidonic acid (ARA), and docosahexaenoic acid (DHA), which potentially give rise to the generation of bioactive oxylipins. Oxylipins are oxygenated fatty acid metabolites that are involved in an assortment of biological functions regulating neurological health and disease. Since it is not known which oxylipins are generated by human brain microvessel endothelial cells (HBMECs), they were incubated for up to 30 min in the absence or presence of 0.1-mM ARA, eicosapentaenoic acid (EPA) or DHA bound to albumin (1:1 molar ratio), and the oxylipins generated were examined using high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Of 135 oxylipins screened in the media, 63 were present at >0.1 ng/mL at baseline, and 95 were present after incubation with fatty acid. Oxylipins were rapidly generated and reached maximum levels by 2-5 min. While ARA, EPA and DHA each stimulated the production of oxylipins derived from these fatty acids themselves, ARA also stimulated the production of oxylipins from endogenous 18- and 20-carbon fatty acids, including α-linolenic acid. Oxylipins generated by the lipoxygenase pathway predominated both in resting and stimulated states. Oxylipins formed via the cytochrome P450 pathway were formed primarily from DHA and EPA, but not ARA. These data indicate that HBMECs are capable of generating a plethora of bioactive lipids that have the potential to modulate BBB endothelial cell function. PMID:26439837

  12. Modulation of arachidonic Acid metabolism in the rat kidney by sulforaphane: implications for regulation of blood pressure.

    Science.gov (United States)

    Elbarbry, Fawzy; Vermehren-Schmaedick, Anke; Balkowiec, Agnieszka

    2014-01-01

    Background. We investigated the effects of sulforaphane (SF), the main active isothiocyanate in cruciferous vegetables, on arachidonic acid (AA) metabolism in the kidney and its effect on arterial blood pressure, using spontaneously hypertensive rats (SHR) as models. Methods. Rats were treated for 8 weeks with either drinking water alone (control) or SF (20 or 40 mg/kg) added to drinking water. Mean arterial pressure (MAP) was measured at 7-day intervals throughout the study. At the end of treatment rats were euthanized, and kidneys were harvested to prepare microsomes and measure enzymes involved in regulation of vasoactive metabolites: CYP4A, the key enzyme in the formation of 20-hydroxyeicosatetraenoic acid, and the soluble epoxide hydrolase, which is responsible for the degradation of the vasodilator metabolites such as epoxyeicosatetraenoic acids. Effect of SF on kidney expression of CYP4A was investigated by immunoblotting. Results. We found that treatment with SF leads to significant reductions in both, the expression and activity of renal CYP4A isozymes, as well as the activity of soluble epoxide hydrolase (sEH). Consistent with these data, we have found that treatment with SF resisted the progressive rise in MAP in the developing SHR in a dose-dependent manner. Conclusion. This is the first demonstration that SF modulates the metabolism of AA by both P450 enzymes and sEH in SHR rats. This may represent a novel mechanism by which SF protects SHR rats against the progressive rise in blood pressure. PMID:24734194

  13. Senegalese sole (Solea senegalensis) metamorphic larvae are more sensitive to pseudo-albinism induced by high dietary arachidonic acid levels than post-metamorphic larvae

    OpenAIRE

    Boglino, A.; Wishkerman, A.; Darias, Maria Jose; de la Iglesia, P.; Andree, K. B.; Gisbert, E; Estevez, A

    2014-01-01

    High dietary levels of arachidonic acid (ARA) and its relative proportions with eicosapentaenoic acid (EPA), fed during early larval stages, have been associated with malpigmentation in various flatfish species. This study investigated whether the nutritional induction of pigmentary disorders at larval stages was related to a specific larval period of increased sensitivity to ARA in Senegalese sole (Solea senegalensis Kaup, 1858). Senegalese sole larvae were fed high dietary ARA levels during...

  14. Astrocytes Release Polyunsaturated Fatty Acids by Lipopolysaccharide Stimuli.

    Science.gov (United States)

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

    2016-01-01

    We previously reported that levels of long-chain fatty acids (FAs) including docosahexaenoic acids (DHA) increase in the hypothalamus of inflammatory pain model mice. However, the precise mechanisms underlying the increment of free fatty acids (FFAs) in the brain during inflammation remains unknown. In this study, we characterized FFAs released by inflammatory stimulation in rat primary cultured astrocytes, and tested the involvement of phospholipase A2 (PLA2) on these mechanisms. Lipopolysaccharide (LPS) stimulation significantly increased the levels of several FAs in the astrocytes. Under these conditions, mRNA expression of cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2) in LPS-treated group increased compared with the control group. Furthermore, in the culture media, the levels of DHA and arachidonic acid (ARA) significantly increased by LPS stimuli compared with those of a vehicle-treated control group whereas the levels of saturated FAs (SFAs), namely palmitic acid (PAM) and stearic acid (STA), did not change. In summary, our findings suggest that astrocytes specifically release DHA and ARA by inflammatory conditions. Therefore astrocytes might function as a regulatory factor of DHA and ARA in the brain. PMID:27374285

  15. Menopause-induced uterine epithelium atrophy results from arachidonic acid/prostaglandin E2 axis inhibition-mediated autophagic cell death.

    Science.gov (United States)

    Zhou, Shengtao; Zhao, Linjie; Yi, Tao; Wei, Yuquan; Zhao, Xia

    2016-01-01

    Women experience menopause later in life. Menopause is characterized by dramatically decreased circulating estrogen level secondary to loss of ovarian function and atrophic state of genital organs. However, the molecular mechanisms for this process are not fully understood. In this study, we aimed to investigate the potential molecular mechanisms that underlie menopause-induced uterine endometrial atrophy. Our data showed that autophagy was activated in the uterine epithelial cells of both ovariectomized rats and peri-menopausal females. Endoplasmic reticulum (ER) stress occurred even prior to autophagy induction. Integrated bioinformatics analysis revealed that ER stress induced downstream decreased release of arachidonic acid (AA) and downregulation of AA/prostaglandin E2 (PGE2) axis, which led to Akt/mTOR signaling pathway inactivation. Consequently, autophagosomes were recruited and LC3-dependent autophagy was induced in uterine epithelial cells. Treatment with exogenous E2, PGE2, salubrinal or RNAi-mediated silencing of key autophagy genes could effectively counteract estrogen depletion-induced autophagy. Collectively, autophagy is a critical regulator of the uterine epithelium that accounts for endometrial atrophy after menopause. PMID:27506466

  16. Menopause-induced uterine epithelium atrophy results from arachidonic acid/prostaglandin E2 axis inhibition-mediated autophagic cell death

    Science.gov (United States)

    Zhou, Shengtao; Zhao, Linjie; Yi, Tao; Wei, Yuquan; Zhao, Xia

    2016-01-01

    Women experience menopause later in life. Menopause is characterized by dramatically decreased circulating estrogen level secondary to loss of ovarian function and atrophic state of genital organs. However, the molecular mechanisms for this process are not fully understood. In this study, we aimed to investigate the potential molecular mechanisms that underlie menopause-induced uterine endometrial atrophy. Our data showed that autophagy was activated in the uterine epithelial cells of both ovariectomized rats and peri-menopausal females. Endoplasmic reticulum (ER) stress occurred even prior to autophagy induction. Integrated bioinformatics analysis revealed that ER stress induced downstream decreased release of arachidonic acid (AA) and downregulation of AA/prostaglandin E2 (PGE2) axis, which led to Akt/mTOR signaling pathway inactivation. Consequently, autophagosomes were recruited and LC3-dependent autophagy was induced in uterine epithelial cells. Treatment with exogenous E2, PGE2, salubrinal or RNAi-mediated silencing of key autophagy genes could effectively counteract estrogen depletion-induced autophagy. Collectively, autophagy is a critical regulator of the uterine epithelium that accounts for endometrial atrophy after menopause. PMID:27506466

  17. The effects of centrally injected arachidonic acid on respiratory system: Involvement of cyclooxygenase to thromboxane signaling pathway.

    Science.gov (United States)

    Erkan, Leman Gizem; Guvenc, Gokcen; Altinbas, Burcin; Niaz, Nasir; Yalcin, Murat

    2016-05-01

    Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the phospholipids of the cell membranes of the body and is abundant in the brain. Exogenously administered AA has been shown to affect brain metabolism and to exhibit cardiovascular and neuroendocrine actions. However, little is known regarding its respiratory actions and/or central mechanism of its respiratory effects. Therefore, the present study was designed to investigate the possible effects of centrally injected AA on respiratory system and the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway on AA-induced respiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA induced dose- and time-dependent increase in tidal volume, respiratory rates and respiratory minute ventilation and also caused an increase in partial oxygen pressure (pO2) and decrease in partial carbon dioxide pressure (pCO2) in male anaesthetized Spraque Dawley rats. I.c.v. pretreatment with ibuprofen, a non-selective COX inhibitor, completely blocked the hyperventilation and blood gases changes induced by AA. In addition, central pretreatment with different doses of furegrelate, a TXA2 synthesis inhibitor, also partially prevented AA-evoked hyperventilation and blood gases effects. These data explicitly show that centrally administered AA induces hyperventilation with increasing pO2 and decreasing pCO2 levels which are mediated by the activation of central COX to TXA2 signaling pathway. PMID:26767978

  18. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    1997-01-01

    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  19. COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.

    Science.gov (United States)

    Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N

    2016-08-15

    Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. PMID:26335394

  20. Arachidonic acid drives postnatal neurogenesis and elicits a beneficial effect on prepulse inhibition, a biological trait of psychiatric illnesses.

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    Motoko Maekawa

    Full Text Available Prepulse inhibition (PPI is a compelling endophenotype (biological markers for mental disorders including schizophrenia. In a previous study, we identified Fabp7, a fatty acid binding protein 7 as one of the genes controlling PPI in mice and showed that this gene was associated with schizophrenia. We also demonstrated that disrupting Fabp7 dampened hippocampal neurogenesis. In this study, we examined a link between neurogenesis and PPI using different animal models and exploring the possibility of postnatal manipulation of neurogenesis affecting PPI, since gene-deficient mice show biological disturbances from prenatal stages. In parallel, we tested the potential for dietary polyunsaturated fatty acids (PUFAs, arachidonic acid (ARA and/or docosahexaenoic acid (DHA, to promote neurogenesis and improve PPI. PUFAs are ligands for Fabp members and are abundantly expressed in neural stem/progenitor cells in the hippocampus. Our results are: (1 an independent model animal, Pax6 (+/- rats, exhibited PPI deficits along with impaired postnatal neurogenesis; (2 methylazoxymethanol acetate (an anti-proliferative drug elicited decreased neurogenesis even in postnatal period, and PPI defects in young adult rats (10 weeks when the drug was given at the juvenile stage (4-5 weeks; (3 administering ARA for 4 weeks after birth promoted neurogenesis in wild type rats; (4 raising Pax6 (+/- pups on an ARA-containing diet enhanced neurogenesis and partially improved PPI in adult animals. These results suggest the potential benefit of ARA in ameliorating PPI deficits relevant to psychiatric disorders and suggest that the effect may be correlated with augmented postnatal neurogenesis.

  1. Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome

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    Taha Ameer Y

    2012-10-01

    Full Text Available Abstract Background In animal models, the metabolic syndrome elicits a cerebral response characterized by altered phospholipid and unesterified fatty acid concentrations and increases in pro-apoptotic inflammatory mediators that may cause synaptic loss and cognitive impairment. We hypothesized that these changes are associated with phospholipase (PLA2 enzymes that regulate arachidonic (AA, 20:4n-6 and docosahexaenoic (DHA, 22:6n-6 acid metabolism, major polyunsaturated fatty acids in brain. Male Wistar rats were fed a control or high-sucrose diet for 8 weeks. Brains were assayed for markers of AA metabolism (calcium-dependent cytosolic cPLA2 IVA and cyclooxygenases, DHA metabolism (calcium-independent iPLA2 VIA and lipoxygenases, brain-derived neurotrophic factor (BDNF, and synaptic integrity (drebrin and synaptophysin. Lipid concentrations were measured in brains subjected to high-energy microwave fixation. Results The high-sucrose compared with control diet induced insulin resistance, and increased phosphorylated-cPLA2 protein, cPLA2 and iPLA2 activity and 12-lipoxygenase mRNA, but decreased BDNF mRNA and protein, and drebrin mRNA. The concentration of several n-6 fatty acids in ethanolamine glycerophospholipids and lysophosphatidylcholine was increased, as was unesterified AA concentration. Eicosanoid concentrations (prostaglandin E2, thromboxane B2 and leukotriene B4 did not change. Conclusion These findings show upregulated brain AA and DHA metabolism and reduced BDNF and drebrin, but no changes in eicosanoids, in an animal model of the metabolic syndrome. These changes might contribute to altered synaptic plasticity and cognitive impairment in rats and humans with the metabolic syndrome.

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

    International Nuclear Information System (INIS)

    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 370C for 15 min with 14C-AA (5 x 10-5M) 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 14C-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 PGE2. 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

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

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    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.

  4. Nitro-Arachidonic Acid Prevents Angiotensin II-Induced Mitochondrial Dysfunction in a Cell Line of Kidney Proximal Tubular Cells.

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    Beatriz Sánchez-Calvo

    Full Text Available Nitro-arachidonic acid (NO2-AA is a cell signaling nitroalkene that exerts anti-inflammatory activities during macrophage activation. While angiotensin II (ANG II produces an increase in reactive oxygen species (ROS production and mitochondrial dysfunction in renal tubular cells, little is known regarding the potential protective effects of NO2-AA in ANG II-mediated kidney injury. As such, this study examines the impact of NO2-AA on ANG II-induced mitochondrial dysfunction in an immortalized renal proximal tubule cell line (HK-2 cells. Treatment of HK-2 cells with ANG II increases the production of superoxide (O2●-, nitric oxide (●NO, inducible nitric oxide synthase (NOS2 expression, peroxynitrite (ONOO- and mitochondrial dysfunction. Using high-resolution respirometry, it was observed that the presence of NO2-AA prevented ANG II-mediated mitochondrial dysfunction. Attempting to address mechanism, we treated isolated rat kidney mitochondria with ONOO-, a key mediator of ANG II-induced mitochondrial damage, in the presence or absence of NO2-AA. Whereas the activity of succinate dehydrogenase (SDH and ATP synthase (ATPase were diminished upon exposure to ONOO-, they were restored by pre-incubating the mitochondria with NO2-AA. Moreover, NO2-AA prevents oxidation and nitration of mitochondrial proteins. Combined, these data demonstrate that ANG II-mediated oxidative damage and mitochondrial dysfunction is abrogated by NO2-AA, identifying this compound as a promising pharmacological tool to prevent ANG II-induced renal disease.

  5. 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

  6. Positive Selection on a Regulatory Insertion–Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid

    Science.gov (United States)

    Kothapalli, Kumar S. D.; Ye, , Kaixiong; Gadgil, Maithili S.; Carlson, Susan E.; O’Brien, Kimberly O.; Zhang, Ji Yao; Park, Hui Gyu; Ojukwu, Kinsley; Zou, James; Hyon, Stephanie S.; Joshi, Kalpana S.; Gu, Zhenglong; Keinan, Alon; Brenna, J.Thomas

    2016-01-01

    Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion–deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product–precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice. PMID:27188529

  7. Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid.

    Science.gov (United States)

    Kothapalli, Kumar S D; Ye, Kaixiong; Gadgil, Maithili S; Carlson, Susan E; O'Brien, Kimberly O; Zhang, Ji Yao; Park, Hui Gyu; Ojukwu, Kinsley; Zou, James; Hyon, Stephanie S; Joshi, Kalpana S; Gu, Zhenglong; Keinan, Alon; Brenna, J Thomas

    2016-07-01

    Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion-deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product-precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice. PMID:27188529

  8. Increased concentrations of arachidonic acid, prostaglandins E2, D2, and 6-oxo-F1 alpha, and histamine in human skin following UVA irradiation

    International Nuclear Information System (INIS)

    The buttock skin of clinically normal human subjects was subjected to approximately 2.5 minimal erythema doses of ultraviolet A irradiation. Deep red erythema developed during irradiation, faded slightly within the next few hours, increased to maximum intensity between 9-15 h, and decreased gradually thereafter although still persisting strongly at 48 h. Suction blister exudates were obtained at 0, 5, 9, 15, 24, and 48 h after irradiation as well as suction blister exudates from a contralateral control site and assayed for arachidonic acid, prostaglandins D2 and E2, and the prostacyclin breakdown product 6-oxo-prostaglandin F1 alpha by gas chromatography-mass spectrometry, and for histamine by radioenzyme assay. Increased concentrations of arachidonic acid and prostaglandins D2, E2, and 6-oxo-prostaglandin F1 alpha were found maximally between 5-9 h after irradiation, preceding the phase of maximal erythema. Elevations of histamine concentration occurred 9-15 h after irradiation, preceding and coinciding with the phase of maximal erythema. At 24 h, still at the height of the erythemal response, all values had returned to near control levels. Hence increased concentrations of arachidonic acid and its products from the cyclooxygenase pathway, and of histamine, accompany the early stages up to 24 h. A causal role in production of the erythema seems likely for these substances although other mediators are almost certainly involved

  9. Effect of some saturated and unsaturated fatty acids on prostaglandin biosynthesis in washed human blood platelets from (1-/sup 14/ C)arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, K.C.; Awasthi, K.K.; Lindegard, P.; Tiwari, K.P.

    1982-03-01

    The effects of some saturated (lauric, palmitic and stearic) an unsaturated (linoleic, gamma-linolenic, alpha-linolenic and oleic) fatty acids at 0.1. 0.25 and 0.5 mM concentrations on the in vitro metabolization of (1-14 C) arachidonic acid by washed human blood platelets have been studied. Effects of these fatty acids were studied with intact as well as lysed platelet preparations. With intact platelet preparations it was found that (i) all unsaturated fatty acids enhanced the biosynthesis of TxB2, PGE2, PGD2 and PGF2 alpha, (ii) unsaturated fatty acids reduced the formation of HHT and HETE with the exception of oleic acid which showed very little effect, (iii) unsaturated fatty acids reduced the formation of MDA, whereas palmitic and stearic acids increased its formation and (iv) all unsaturated fatty acids reduced the synthesis of prostaglandin endoperoxides. These results support our previous observations where effects of fatty acids were examined at higher concentrations (10). At 0.1 mM FA concentration, inconsistent results were obtained. With lysed platelet preparations all cyclooxygenase products were reduced in presence of unsaturated fatty acids, whereas HETE formation was reduced only in presence of linoleic and gamma-linolenic acids. Electron micrographs of washed platelet suspensions were obtained with untreated platelet preparations and platelet preparations treated with 0.25 and 0.5 mM linoleic acid concentrations. The results are discussed in the light of a possible soap-like effect of FA salt on platelets.

  10. 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.

  11. Effects of arachidonic acid intake on inflammatory reactions in dextran sodium sulphate-induced colitis in rats.

    Science.gov (United States)

    Naito, Yukiko; Ji, Xu; Tachibana, Shigehiro; Aoki, Satoko; Furuya, Mami; Tazura, Yoshiyuki; Miyazawa, Daisuke; Harauma, Akiko; Moriguchi, Toru; Nagata, Tomoko; Iwai, Naoharu; Ohara, Naoki

    2015-09-14

    The aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease. PMID:26234346

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

    Science.gov (United States)

    De Souza, Eduardo O.; Lowery, Ryan P.; Wilson, Jacob M.; Sharp, Matthew H.; Mobley, Christopher Brooks; Fox, Carlton D.; Lopez, Hector L.; Shields, Kevin A.; Rauch, Jacob T.; Healy, James C.; Thompson, Richard M.; Ormes, Jacob A.; Joy, Jordan M.; Roberts, Michael D.

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:27182886

  13. Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2

    OpenAIRE

    Mulugeta, Surafel; Suzuki, Takashi; Hernandez, Noemi Tejera; Griesser, Markus; Boeglin, William E; Schneider, Claus

    2010-01-01

    Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX) enzymes is accompanied by formation of a small amount of 11R-hydroxyeicosatetraenoic acid (HETE), 15R-HETE, and 15S-HETE as by-products. Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers formation of 15R-HETE as the sole product of oxygenation of arachidonic acid. Here, we investigated the formation of by-products of the transformation of 5S-HETE by native COX-2 and by aspirin-acetylated CO...

  14. Arachidonic acid has a dominant effect to regulate lipogenic genes in 3T3-L1 adipocytes compared to omega-3 fatty acids

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    Hitesh Vaidya

    2015-03-01

    Full Text Available Background: The effects of long-chain n-3 and n-6 polyunsaturated fatty acids (PUFA on the regulation of adipocytes metabolism are well known. These fatty acids are generally consumed together in our diets; however, the metabolic regulation of adipocytes in the presence of these fatty acids when given together is not known. Objective: To investigate the effects of n-3 PUFA and arachidonic acid (AA, an n-6 PUFA, on the regulation of adipogenic and lipogenic genes in mature 3T3-L1 adipocytes. Methods: 3T3-L1 adipocytes were incubated in the presence or absence of 100 µM of eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA; docosapentaenoic acid, DPA and AA, either alone or AA+n-3 PUFA; control cells received bovine serum albumin alone. The mRNA expression of adipogenic and lipogenic genes was measured. The fatty acid composition of adipocytes was analyzed using gas chromatography. Results: Individual n-3 PUFA or AA had no effect on the mRNA expression of peroxisome-proliferator-activated receptor-γ; however, AA+EPA and AA+DPA significantly increased (P<0.05 the expression compared to control cells (38 and 42%, respectively. AA and AA+EPA increased the mRNA expression of acetyl-CoA carboxylase 1 (P<0.05. AA treatment decreased the mRNA expression of stearoyl-CoA desaturase (SCD1 (P<0.01, while n-3 PUFA, except EPA, had no effect compared to control cells. AA+DHA and AA+DPA inhibited SCD1 gene expression (P<0.05 suggesting a dominant effect of AA. Fatty acids analysis of adipocytes revealed a higher accretion of AA compared to n-3 PUFA. Conclusions: Our findings reveal that AA has a dominant effect on the regulation of lipogenic genes in adipocytes.

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

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    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.

  16. Incorporation of arachidonic acid (AA) into phosphatidylcholine molecular species of the human neutrophil (PMN)

    International Nuclear Information System (INIS)

    Recently the authors proposed that the initial incorporation of AA into 1,2 diacylphosphatidylcholine (PC) was mediated by AA-CoA transferase(s) while the subsequent transfer of AA from 1,2-diacyl- into alkyl, acyl-PC was mediated by a CoA-independent transacylase. Studies here provide further evidence for such a two-step mechanism. PMNs were pulse labeled for 5 min with 3H-AA (.07μM) which was rapidly incorporated into 1,2-diacyl-PC. However, incorporation of AA into 1,2-diacyl-PC was inhibited by incubation with high levels of AA (30 μM). Similarly PMNs were pulsed labeled with 3H-AA for 5 min followed by a 120 min incubation. In these cells, 3H-AA was rapidly transferred from 1,2-diacyl-PC into alkyl, acyl-PC. In the presence of 30 μM AA redistribution of 3H-AA from diacyl to alkyl, acyl-PC was observed. This result implied that the initial incorporation of 3H-AA proceeds via a free acid intermediate while the transfer of 3H-AA from diacyl to alkyl, acyl-PC does not. Using a cell free system, 14C-AACoA was incubated for 5 min and found to be incorporated into 1,2-diacyl-PC containing 16:0, 18:0, and 18:1 at the sn-1 position. Furthermore 14C-AACoA and various 1-radyl, 2-lyso-PC were added to a PMN membrane preparation. The arachidonyl-transferase(s) preferred the 1-acyl, 2-lyso-PC substrate to 1-alkyl, 2-lyso-PC. Thus these studies provide further evidence that AA is initially incorporated into 1,2-diacyl-PC through arachidonyl-CoA transferases

  17. Long-term modifications of blood pressure in normotensive and spontaneously hypertensive rats by gene delivery of rAAV-mediated cytochrome P450 arachidonic acid hydroxylase

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Arachidonic acid cytochrome P-450 (CYP) hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adenoassociated viral vector (rAAV) to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHR), respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hypertension. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV.4A1-treated SD rats and decreased by 13.7±2.2 mm Hg in rAAV.anti4A1-treated SHR rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mRNA and protein levels. In anti-4A1-treated SHR, CYP4A mRNA in various tissues was probed, especially in kidneys,but 4A1 protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxylases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension.rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hypertension by blocking expression of CYP 4A in kidneys.

  18. FATTY ACIDS PROFILE IN A HIGH CELL DENSITY CULTURE OF ARACHIDONIC ACID-RICH PARIETOCHLORIS INCISA (TREBOUXIOPHYCEAE,CHLOROPHYTA) EXPOSED TO HIGH PFD

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The changes in arachidonic acid (AA) and fatty acids profiles along the growth curve of Parietochloris incisa, a coccoid snow green alga, were studied in a 2.8 cm light-path flat photobioreactor, exposed to strong photon flux density [PFD, 2400 μEmol/(m2*s)]. Sixteen fatty acids were identified by gas chromatography showing that AA was the dominant fatty acid (33%-41%) followedby linoleic acid (17%-21%). AA content was closely investigated with respect tototal fatty acids (TFA), ash free dry weight (AFDW) of cell mass as well as total culture content. These parameters were influenced significantly in a similar manner by culture growth phase, i.e., slightly decreasing in the lag period, gradually increasing in the logarithmic phase, becoming maximal at the early stationary phase, starting to decrease at the late stationary phase, sharply dropping at the decline phase. The increase in AA per culture volume during the logarithmic phase was not only associated with the increase in AFDW but also connected with a corresponding increase in AA/TFA, TFA/AFDW as well as AA/AFDW. The sharp decrease in AA content of the culture during the decline phase was mainly due to the decrease in AA/TFA, TFA/AFDW and AA/AFDW, although AFDW declined only a smallextent. Maximal AA concentration, obtained at the early stationary phase, was 900 mg/L culture volume, and the average daily net increase of AA during 9 days logarithmic growth was 1.7 g/(m2*day). Therefore, harvesting prior to the declinephase in a batch culture, or at steady state in continuous culture mode seems best for high AA production. The latter possibility was also further confirmed bycontinuous culture with 5 gradients of harvesting rate. ``

  19. The combined impact of plant-derived dietary ingredients and acute stress on the intestinal arachidonic acid cascade in Atlantic salmon (Salmo salar)

    OpenAIRE

    Oxley, Anthony; Jolly, Cecile; Eide, Torunn; Jordal, Ann-Elise O.; Svardal, Asbjørn Martin; Olsen, Rolf Erik

    2010-01-01

    A study was conducted to assess the effect of substituting high levels of dietary fish oil (FO) and fishmeal (FM) for vegetable oil (VO) and plant protein (PP) on the intestinal arachidonic acid (AA) cascade in the carnivorous fish species Atlantic salmon. Four diets were fed to salmon over a period of 12 months, including a control FMFO diet, with varying replacements of plant-derived ingredients: 80 % PP and 35 % VO; 40 % PP and 70 % VO; 80 % PP and 70 %VO. Subsequently, fish were examined ...

  20. Ca-mediated and independent effects of arachidonic acid on gap junctions and Ca-independent effects of oleic acid and halothane.

    Science.gov (United States)

    Lazrak, A; Peres, A; Giovannardi, S; Peracchia, C

    1994-09-01

    In Novikoff hepatoma cell pairs studied by double perforated patch clamp (DPPC), brief (20 s) exposure to 20 microM arachidonic acid (AA) induced a rapid and reversible uncoupling. In pairs studied by double whole-cell clamp (DWCC), uncoupling was completely prevented by effective buffering of Cai2+ with BAPTA. Similarly, AA (20 s) had no effect on coupling in cells perfused with solutions containing no added Ca2+ (SES-no-Ca) and studied by DPPC, suggesting that Ca2+ influx plays an important role. Parallel experiments monitoring [Ca2+]i with fura-2 showed that [Ca2+]i increases with AA to 0.7-1.5 microM in normal [Ca2+]o, and to approximately 400 nM in SES-no-Ca solutions. The rate of [Ca2+]i increase matched that of Gj decrease, but [Ca2+]i recovery was faster. In cells studied by DWCC with 2 mM BAPTA in the pipette solution and superfused with SES-no-Ca, long exposure (1 min) to 20 microM AA caused a slow and virtually irreversible uncoupling. This result suggests that AA has a dual mechanism of uncoupling: one dominant, fast, reversible, and Ca(2+)-dependent, the other slow, poorly reversible, and Ca(2+)-independent. In contrast, uncoupling by oleic acid (OA) or halothane was insensitive to internal buffering with BAPTA, suggesting a Ca(2+)-independent mechanism only. PMID:7811915

  1. 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

    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...

  2. Organochlorine insecticides induce NADPH oxidase-dependent reactive oxygen species in human monocytic cells via phospholipase A2/arachidonic acid.

    Science.gov (United States)

    Mangum, Lee C; Borazjani, Abdolsamad; Stokes, John V; Matthews, Anberitha T; Lee, Jung Hwa; Chambers, Janice E; Ross, Matthew K

    2015-04-20

    ) levels and enhanced p47(phox) membrane localization compared to that in vehicle-treated cells. p47(phox) is a cytosolic regulatory subunit of Nox, and its phosphorylation and translocation to the NOX2 catalytic subunit in membranes is a requisite step for Nox assembly and activation. Dieldrin and trans-nonachlor treatments of monocytes also resulted in marked increases in arachidonic acid (AA) and eicosanoid production, which could be abrogated by the phospholipase A2 (PLA2) inhibitor arachidonoyltrifluoromethyl ketone (ATK) but not by calcium-independent PLA2 inhibitor bromoenol lactone. This suggested that cytosolic PLA2 plays a crucial role in the induction of Nox activity by increasing the intracellular pool of AA that activates protein kinase C, which phosphorylates p47(phox). In addition, ATK also blocked OC-induced p47(phox) serine phosphorylation and attenuated ROS levels, which further supports the notion that the AA pool liberated by cytosolic PLA2 is responsible for Nox activation. Together, the results suggest that trans-nonachlor and dieldrin are capable of increasing intracellular superoxide levels via a Nox-dependent mechanism that relies on elevated intracellular AA levels. These findings are significant because chronic activation of monocytes by environmental toxicants might contribute to pathogenic oxidative stress and inflammation. PMID:25633958

  3. Short-term diets rich in arachidonic acid influence plasma phospholipid polyunsaturated fatty acid levels and prostacyclin and thromboxane production in humans.

    Science.gov (United States)

    Sinclair, A J; Mann, N J

    1996-04-01

    Two small-scale dietary intervention studies were conducted to examine the effect of diets rich in arachidonic acid (AA) and n-3 long-chain polyunsaturated fatty acids (n-3 LCP), on the in vivo production of prostacyclin (PGI2) and thromboxane (TXA2). The first was a pilot study and contained insufficient numbers for statistical analyses. It involved a 7-d intervention with 10 subjects divided into three groups, consuming diets rich in AA (500 mg/d), rich in AA and docosahexaenoic acid (DHA) (500 mg/d of each), or rich in DHA and eicosapentaenoic acid (EPA) (approximately 1500 mg/d of n-3 LCP). Plasma phospholipid (PL) levels of AA increased in all subjects in groups 1 (n = 4) and 2 (n = 3). DHA levels increased in all subjects in Groups 2 and 3 (n = 3), and EPA levels increased in all subjects from Group 3 but fell in all subjects from Group 1. The in vivo production of PGI2, measured as its urinary metabolite, was increased in two subjects in Group 1 and one subject in Group 2, with all other subjects showing little change. Urinary TXA2 metabolite increased in all subjects from Group 1. The second study was conducted in seven subjects, who consumed a low fat diet for 2 wk: the 1st wk was a vegetarian diet (no LCP) followed by a 2nd wk where the subjects were required to consume 500 g (raw weight) of kangaroo meat daily (305 mg/d AA, 325 mg/d n-3 LCP). The meat diet was associated with a marked rise in the serum PL levels of AA, EPA and docosapentaenoic acid 22:5(n-3) and with a significant increase in the urinary output of the prostacyclin metabolite, but no effect on TXA2 production, as measured by its urinary metabolite level. The results of these studies have shown that diets that contain both AA and n-3 LCP are associated with an increase in PGI2 production, without affecting TXA2 production. Further studies with purified LCP are warranted. PMID:8642442

  4. Effect of NC-1900, an active fragment analog of arginine vasopressin, and inhibitors of arachidonic acid metabolism on performance of a passive avoidance task in mice.

    Science.gov (United States)

    Sato, Tomoaki; Ishida, Takayuki; Irifune, Masahiro; Tanaka, Koh-ichi; Hirate, Kenji; Nakamura, Norifumi; Nishikawa, Takashige

    2007-03-29

    In this study, we investigated the effect of administration of inhibitors of each of the arachidonic acid metabolism pathways and the effect of co-administration of these inhibitors with NC-1900, a fragment analog of arginine vasopressin, on step-through passive avoidance task performance. All drugs were administered just after the acquisition trial in the passive avoidance task. Intracerebroventricular (i.c.v.) administration of nordihydroguaiaretic acid (NDGA, 1 and 10 microg), a phospholipase A2 (PLA2) and lipoxygenase (LOX) inhibitor, and of arachidonyl trifluoromethyl ketone (ATK, 1 and 10 microg), a specific PLA2 inhibitor caused reductions in latency on the retention trial. The i.c.v. administration of either of baicalein (0.1-10 microg), a 12-LOX inhibitor, or AA-861 (0.1-10 microg), a 5-LOX inhibitor, did not influence the latency. Intraperitoneal administration of indomethacin (20 mg/kg), a non-specific COX inhibitor, or NS-398 (10 mg/kg), a specific COX-2 inhibitor, impaired performance on the retention trial in the task, while piroxicam (20 mg/kg), a specific COX-1 inhibitor, did not. Subcutaneous administration of NC-1900 (0.1 ng/kg) ameliorated the reduction of latency caused by NDGA, ATK, indomethacin, or NS-398. These results suggested that the COX-2 pathway of arachidonic acid metabolism may be important for learning and/or memory in the passive avoidance task in mice, and that the ameliorating effect of NC-1900, in part, is due to mimicking of the effects of metabolites of the COX-2 pathway. PMID:17303115

  5. Arachidonic acid production from cane molasses by Mortierella alpina%利用甘蔗糖蜜发酵生产花生四烯酸的研究

    Institute of Scientific and Technical Information of China (English)

    彭超; 黄和; 纪晓俊; 刘欣; 聂志奎; 邓中涛

    2013-01-01

    Arachidonic acid (ARA) fermentation by Mortierella alpina was carried out using cane molasses.Several different preparation methods were investigated to evaluate the optimal process of cane molasses method.The results indicated that sulfuric acid process was the best method.The cultivation parameters were as follows:reducing sugar concentration 80 g/L,nitrogen resource concentration 6 g/L,inoculum density 20%,initial pH 6.0,and cultivation temperature 25 ℃.The resultant dry cell weight,total lipid content,arachidonic acid yield,and sugar utilization were 28.5 g/L,11.7 g/L,3.68 g/L,and 94.5%,respectively.%通过培养高山被孢霉利用糖蜜来发酵生产花生四烯酸(ARA),研究了不同甘蔗糖蜜预处理方法对ARA发酵生产的影响.研究表明:H2S04法是最利于ARA发酵生产的糖蜜预处理方法.利用预处理的甘蔗糖蜜发酵生产ARA,通过单因素实验设计,确定了最优的培养条件,包括初始还原糖80 g/L,N源6g/L,接种量20%,初始pH6.0和培养t温度25℃,在此条件下发酵,干细胞质量、油脂含量、ARA产量和糖利用率分别达到28.5 g/L、11.7g/L、3.68 g/L和94.5%.

  6. 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

    Supplementation of dietary arachidonic acid (ARA) is known to cause hypopigmentation in common sole larvae (Solea solea L.). This study examined a possible link between dietary ARA supplementation - light intensity and tank colour on pigment defects in common sole larvae. Larval tissue ARA and...... prostaglandin PGE(2) content increased significantly when fed Artemia enriched by a fish oil emulsion supplemented with 24% dietary ARA during premetamorphosis (until 11 days post hatch, dph) as compared to larvae fed on Artemia enriched by a fish oil based emulsion. More than 90% of all larvae in groups...... treated with the ARA supplemented emulsion during premetamorphosis showed partly or complete dorsal hypopigmentation. There were no significant effects of light intensity or tank background colour in combination with ARA on malpigmentation. Larval hypopigmentation was below 10% in the groups not treated...

  7. Acetyl eugenol, a component of oil of cloves (Syzygium aromaticum L.) inhibits aggregation and alters arachidonic acid metabolism in human blood platelets.

    Science.gov (United States)

    Srivastava, K C; Malhotra, N

    1991-01-01

    In continuation of our studies with the oil of cloves--a common kitchen spice and a crude drug for home medicine--we have isolated yet another active component identified as acetyl eugenol (AE); the earlier reported active component being eugenol. The isolated material (IM) was found to be a potent platelet inhibitor; IM abolished arachidonate (AA)-induced aggregation at ca. 12 microM, a concentration needed to abolish the second phase of adrenaline-induced aggregation. Chemically synthesized acetyl eugenol showed similar effects on AA- and adrenaline-induced aggregation. A dose-dependent inhibition of collagen-induced aggregation was also observed. AE did not inhibit either calcium ionophore A23187- or thrombin-induced aggregation. Studies on aggregation and ATP release were done using whole blood (WB). AA-induced aggregation in WB was abolished at 3 micrograms/ml (14.6 microM) which persisted even after doubling the concentration of AA. ATP release was inhibited. Inhibition of aggregation appeared to be mediated by a combination of two effects: reduced formation of thromboxane and increased generation of 12-lipoxygenase product (12-HPETE). These effects were observed by exposing washed platelets to (14C)AA or by stimulating AA-labelled platelets with ionophore A23187. Acetyl eugenol inhibited (14C)TxB2 formation in AA-labelled platelets on stimulation with thrombin. AE showed no effect on the incorporation of AA into platelet phospholipids. PMID:2011614

  8. A liquid chromatography/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in rat brain tissue.

    Science.gov (United States)

    Yue, Hongfei; Jansen, Susan A; Strauss, Kenneth I; Borenstein, Michael R; Barbe, Mary F; Rossi, Luella J; Murphy, Elise

    2007-02-19

    A sensitive, specific, and robust liquid chromatography/mass spectrometric (LC/MS) method was developed and validated that allows simultaneous analysis of arachidonic acid (AA) and its cyclooxygenase, cytochrome P450, and lipoxygenase pathway metabolites prostaglandins (PGs), dihydroxyeicosatrienoic acids (DiHETrEs), hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs), including PGF(2alpha), PGE(2), PGD(2), PGJ(2), 14,15-DiHETrE, 11,12-DiHETrE, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 9-HETE, 8-HETE, 5-HETE, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET in rat brain tissues. Deuterium labeled PGF(2alpha)-d(4), PGD(2)-d(4), 15(S)-HETE-d(8), 14,15-EET-d(8), 11,12-EET-d(8), 8,9-EET-d(8), and AA-d(8) were used as internal standards. Solid phase extraction was used for sample preparation. A gradient LC/MS method using a C18 column and electrospray ionization source under negative ion mode was optimized for the best sensitivity and separation within 35 min. The method validation, including LC/MS instrument qualification, specificity, calibration model, accuracy, precision (without brain matrix and with brain matrix), and extraction efficiency were performed. The linear ranges of the calibration curves were 2-1000 pg for PGs, DiHETrEs, HETEs, and EETs, 10-2400 pg for PGE(2) and PGD(2), and 20-2000 ng for AA, respectively. PMID:17125954

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying; Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zheng, Hao; Yu, Wei; Chai, Hongyan [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390,USA (United States); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yue, Jiang; Peng, Renxiu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2013-10-01

    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{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B{sub 4} (LTB{sub 4}). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser{sup 241}), phospho-Akt (Thr{sup 308}), phospho-Bad (Ser{sup 136}), and Bcl-x{sub L} expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE{sub 2}, LTB{sub 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{sup 308}). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic

  10. 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)

    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 E2 (PGE2) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B4 (LTB4). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser241), phospho-Akt (Thr308), phospho-Bad (Ser136), and Bcl-xL expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE2, LTB4 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 (Thr308). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer

  11. Epoxyeicosatrienoic acids are endogenous regulators of vasoactive neuropeptide release from trigeminal ganglion neurons.

    Science.gov (United States)

    Iliff, Jeffrey J; Fairbanks, Stacy L; Balkowiec, Agnieszka; Alkayed, Nabil J

    2010-12-01

    Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. We previously described the expression of cytochrome P450-2J epoxygenase in rat trigeminal ganglion neurons and that EETs signaling is involved in cerebrovascular dilation resulting from perivascular nerve stimulation. In this study, we evaluate the presence of the EETs signaling pathway in trigeminal ganglion neurons and their role in modulating the release of calcitonin gene-related peptide (CGRP) by trigeminal ganglion neurons. Liquid chromatography tandem mass spectrometry identified the presence of each of the four EETs regio-isomers within primary trigeminal ganglion neurons. Stimulation for 1 h with the transient receptor potential vanilloid-1 channel agonist capsaicin (100 nmol/L) or depolarizing K(+) (60 mmol/L) increased CGRP release as measured by ELISA. Stimulation-evoked CGRP release was attenuated by 30 min pre-treatment with the EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol/L). K(+) stimulation elevated CGRP release 2.9 ± 0.3-fold above control levels, whereas in the presence of 14,15-EEZE K(+)-evoked CGRP release was significantly reduced to 1.1 ± 0.2-fold above control release (p < 0.01 anova, n = 6). 14,15-EEZE likewise attenuated capsaicin-evoked CGRP release from trigeminal ganglion neurons (p < 0.05 anova, n = 6). Similarly, pre-treatment with the cytochrome P450 epoxygenase inhibitor attenuated stimulation-evoked CGRP release. These data demonstrate that EETs are endogenous constituents of rat trigeminal ganglion neurons and suggest that they may act as intracellular regulators of neuropeptide release, which may have important clinical implications for treatment of migraine, stroke and vasospasm after subarachnoid hemorrhage. PMID:20950340

  12. Epoxyeicosatrienoic Acids (EETs) are Endogenous Regulators of Vasoactive Neuropeptide Release from Trigeminal Ganglion Neurons

    Science.gov (United States)

    Iliff, Jeffrey J.; Fairbanks, Stacy L.; Balkowiec, Agnieszka; Alkayed, Nabil J.

    2010-01-01

    Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. We previously described the expression of CYP-2J epoxygenase in rat trigeminal ganglion neurons and that EETs signaling is involved in cerebrovascular dilation resulting from perivascular nerve stimulation. Herein we evaluate the presence of the EETs signaling pathway in trigeminal ganglion neurons and their role in modulating the release of calcitonin gene-related peptide (CGRP) by trigeminal ganglion neurons. Liquid chromatography tandem mass spectrometry identified the presence of each of the four EETs regio-isomers within primary trigeminal ganglion neurons. Stimulation for one hour with the transient receptor potential vanilloid-1 channel agonist capsaicin (100 nmol/L) or depolarizing K+ (60 mmol/L) increased CGRP release as measured by ELISA. Stimulation-evoked CGRP release was attenuated by 30 min pre-treatment with the EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol/L). K+ stimulation elevated CGRP release 2.9 ± 0.3-fold above control levels, while in the presence of 14,15-EEZE K+-evoked CGRP release was significantly reduced to 1.1 ± 0.2-fold above control release (p<0.01 ANOVA, n=6). 14,15-EEZE likewise attenuated capsaicin-evoked CGRP release from trigeminal ganglion neurons (p<0.05 ANOVA, n=6). Similarly, pre-treatment with the CYP epoxygenase inhibitor attenuated stimulation-evoked CGRP release. These data demonstrate that EETs are endogenous constituents of rat trigeminal ganglion neurons and suggest that they may act as intracellular regulators of neuropeptide release, which may have important clinical implications for treatment of migraine, stroke and vasospasm after subarachnoid hemorrhage. PMID:20950340

  13. 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. PMID:27138971

  14. Increased arachidonic acid-containing phosphatidylcholine is associated with reactive microglia and astrocytes in the spinal cord after peripheral nerve injury.

    Science.gov (United States)

    Xu, Dongmin; Omura, Takao; Masaki, Noritaka; Arima, Hideyuki; Banno, Tomohiro; Okamoto, Ayako; Hanada, Mitsuru; Takei, Shiro; Matsushita, Shoko; Sugiyama, Eiji; Setou, Mitsutoshi; Matsuyama, Yukihiro

    2016-01-01

    Peripheral nerve injury (PNI) triggers cellular and molecular changes in the spinal cord. However, little is known about how the polyunsaturated fatty acid-containing phosphatidylcholines (PUFA-PCs) are regulated in the spinal cord after PNI and the association of PUFA-PCs with the non-neuronal cells within in the central nervous system (CNS). In this study, we found that arachidonic acid-containing phosphatidylcholine (AA-PC), [PC(16:0/20:4)+K](+), was significantly increased in the ipsilateral ventral and dorsal horns of the spinal cord after sciatic nerve transection, and the increased expression of [PC(16:0/20:4)+K](+) spatiotemporally resembled the increase of reactive microglia and the astrocytes. From the lipidomics point of view, we conclude that [PC(16:0/20:4)+K](+) could be the main phospholipid in the spinal cord influenced by PNI, and the regulation of specific phospholipid molecule in the CNS after PNI is associated with the reactive microglia and astrocytes. PMID:27210057

  15. 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.

  16. 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.

  17. High extracellular Ca2+ stimulates Ca2+-activated Cl- currents in frog parathyroid cells through the mediation of arachidonic acid cascade.

    Directory of Open Access Journals (Sweden)

    Yukio Okada

    Full Text Available Elevation of extracellular Ca(2+ concentration induces intracellular Ca(2+ signaling in parathyroid cells. The response is due to stimulation of the phospholipase C/Ca(2+ pathways, but the direct mechanism responsible for the rise of intracellular Ca(2+ concentration has remained elusive. Here, we describe the electrophysiological property associated with intracellular Ca(2+ signaling in frog parathyroid cells and show that Ca(2+-activated Cl(- channels are activated by intracellular Ca(2+ increase through an inositol 1,4,5-trisphophate (IP(3-independent pathway. High extracellular Ca(2+ induced an outwardly-rectifying conductance in a dose-dependent manner (EC(50 ∼6 mM. The conductance was composed of an instantaneous time-independent component and a slowly activating time-dependent component and displayed a deactivating inward tail current. Extracellular Ca(2+-induced and Ca(2+ dialysis-induced currents reversed at the equilibrium potential of Cl(- and were inhibited by niflumic acid (a specific blocker of Ca(2+-activated Cl(- channel. Gramicidin-perforated whole-cell recording displayed the shift of the reversal potential in extracellular Ca(2+-induced current, suggesting the change of intracellular Cl(- concentration in a few minutes. Extracellular Ca(2+-induced currents displayed a moderate dependency on guanosine triphosphate (GTP. All blockers for phospholipase C, diacylglycerol (DAG lipase, monoacylglycerol (MAG lipase and lipoxygenase inhibited extracellular Ca(2+-induced current. IP(3 dialysis failed to induce conductance increase, but 2-arachidonoylglycerol (2-AG, arachidonic acid and 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S-HPETE dialysis increased the conductance identical to extracellular Ca(2+-induced conductance. These results indicate that high extracellular Ca(2+ raises intracellular Ca(2+ concentration through the DAG lipase/lipoxygenase pathway, resulting in the activation of Cl(- conductance.

  18. 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

    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......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...... determine pigmentation. Malpigmentation defined as hypomelanosis was significantly related to elevated dietary and larval ARA contents, but not to EPA. The study reports evidence for a pigmentation window, as larval sensitivity to ARA or its derivatives was much higher during pre metamorphosis, than during...

  19. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.

    Science.gov (United States)

    Reddy, I A; Pino, J A; Weikop, P; Osses, N; Sørensen, G; Bering, T; Valle, C; Bluett, R J; Erreger, K; Wortwein, G; Reyes, J G; Graham, D; Stanwood, G D; Hackett, T A; Patel, S; Fink-Jensen, A; Torres, G E; Galli, A

    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 cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA. PMID:27187231

  20. 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)

    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

  1. 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. PMID:20022733

  2. 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

    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...... 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. This...... 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 the...

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

    International Nuclear Information System (INIS)

    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

  4. Role of arachidonic acid and protein kinase C during maturation-inducing hormone-dependent meiotic resumption and ovulation in ovarian follicles of Atlantic croaker

    Science.gov (United States)

    Patino, R.; Yoshizaki, G.; Bolamba, D.; Thomas, P.

    2003-01-01

    The roles of arachidonic acid (AA) and protein kinase C (PKC) during in vitro maturation-inducing hormone (MIH)-dependent meiotic resumption (maturation) and ovulation were studied in ovarian follicles of Atlantic croaker (Micropogonias undulatus). The requirement for cyclooxygenase (COX) metabolites of AA was examined using a nonspecific COX inhibitor, indomethacin (IM), as well as two COX products, prostaglandin (PG) F2?? and PGE2, whereas the role of lipoxygenase (LOX) was investigated using a specific LOX inhibitor, nordihydroguaiaretic acid (NDGA). The involvement of PKC was examined using phorbol 12-myristate 13-acetate (PMA), a PKC activator, as well as GF109203X (GF), a specific inhibitor of PKC and 1-(5-isoquin- olinesulfonyl)-2-methylpiperazine (H7), nonspecific inhibitor of protein kinases. Genomic mechanisms were examined with the transcription-inhibitor actinomycin D (ActD) and the functionality of heterologous (oocyte-granulosa) gap junctions (GJ) with a dye transfer assay. The AA (100 ??M) and PGF2?? (5 ??M) did not induce maturation, and NDGA (10 ??M) did not affect MIH-dependent maturation. However, IM (100 ??M) partially inhibited MIH-dependent maturation. Conversely, AA and both PGs induced, and IM and NDGA inhibited, MIH-dependent ovulation in matured follicles. The PMA (1 ??g/ml) did not induce maturation but caused ovulation in matured follicles, whereas PKC inhibitors (GF, 5 ??M; H7, 50??M) did not affect MIH-dependent maturation but inhibited MIH- and PMA-dependent ovulation. The PMA-dependent ovulation was inhibited by IM but not by NDGA. In addition, ActD (5 ??M) blocked MIH-dependent, but not PMA-dependent, ovulation, and PGF2?? restored MIH-dependent ovulation in ActD-blocked follicles. The AA and PGs did not induce, and GF did not inhibit, MIH-dependent heterologous GJ uncoupling. In conclusion, AA and PKC mediate MIH-dependent ovulation but not meiotic resumption or heterologous GJ uncoupling in croaker follicles, but a permissive role

  5. The application of arachidonic acid in dairy products%花生四烯酸在乳制品中的应用

    Institute of Scientific and Technical Information of China (English)

    詹现璞; 吕银德; 赵俊芳

    2009-01-01

    花生四烯酸(AA)是一种人体必需的多不饱和脂肪酸,是人体生长因子,影响婴幼儿大脑和神经发育.AA具有改善记忆力和视力、调节血脂和血糖、降低血清胆固醇、预防心血管疾病、辅助抑制肿瘤、预防癌变、神经功能调节等作用.人体自身不能合成AA,必需从食物补充才能满足机体代谢的需要,牛乳是人体补充营养物质的载体,而AA在牛乳中几乎不存在,所以在牛乳中强化AA已显得非常必要.本文介绍了AA添加带配方奶粉中的工艺流程和操作要点;AA应用于纯牛奶中的工艺流程和操作要点;开发富含AA酸牛奶的生产工艺和操作要点;开发富含AA乳饮料的工艺流程和操作要点.研究发现,AA在酸牛奶和乳饮料中的应用将是新的发展趋势,富含AA的乳制品将会给企业带来巨大的经济效益和社会效益.%Arachidonic acid(AA)is an essential polyunsaturated fatty acids for human.It is a human growth factor,which can greatly affect infant brain and neurological development.AA can improve the memory and vision,regulate blood lipids and blood sugar,reduce cholesterol,and prevent cardiovascular disease and cancer.AA can not be synthesized by human body,it can only be obtained through food.Milk contains rich nutrients except AA,so AA fortified milk has become necessary.In this paper,the formula and process for adding AA into milk has been studied.It is found that AA in the acidophilus milk and milk drinks will be the new trend of dairy products.AA enrichment products will bring enormous economic and social benefits.

  6. Engineering of a novel hybrid enzyme: an anti-inflammatory drug target with triple catalytic activities directly converting arachidonic acid into the inflammatory prostaglandin E2

    Science.gov (United States)

    Ruan, Ke-He; Cervantes, Vanessa; So, Shui-Ping

    2009-01-01

    Cyclooxygenase isoform-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) are inducible enzymes that become up-regulated in inflammation and some cancers. It has been demonstrated that their coupling reaction of converting arachidonic acid (AA) into prostaglandin (PG) E2 (PGE2) is responsible for inflammation and cancers. Understanding their coupling reactions at the molecular and cellular levels is a key step toward uncovering the pathological processes in inflammation. In this paper, we describe a structure-based enzyme engineering which produced a novel hybrid enzyme that mimics the coupling reactions of the inducible COX-2 and mPGES-1 in the native ER membrane. Based on the hypothesized membrane topologies and structures, the C-terminus of COX-2 was linked to the N-terminus of mPGES-1 through a transmembrane linker to form a hybrid enzyme, COX-2-10aa-mPGES-1. The engineered hybrid enzyme expressed in HEK293 cells exhibited strong triple-catalytic functions in the continuous conversion of AA into PGG2 (catalytic-step 1), PGH2 (catalytic-step 2) and PGE2 (catalytic-step 3), a pro-inflammatory mediator. In addition, the hybrid enzyme was also able to directly convert dihomo-gamma-linolenic acid (DGLA) into PGG1, PGH1 and then PGE1 (an anti-inflammatory mediator). The hybrid enzyme retained similar Kd and Vmax values to that of the parent enzymes, suggesting that the configuration between COX-2 and mPGES-1 (through the transmembrane domain) could mimic the native conformation and membrane topologies of COX-2 and mPGES-1 in the cells. The results indicated that the quick coupling reaction between the native COX-2 and mPGES-1 (in converting AA into PGE2) occurred in a way so that both enzymes are localized near each other in a face-to-face orientation, where the COX-2 C-terminus faces the mPGES-1 N-terminus in the ER membrane. The COX-2-10aa-mPGES-1 hybrid enzyme engineering may be a novel approach in creating inflammation cell and animal models, which

  7. Effects of heparin on platelet aggregation and release and thromboxane A2 production

    International Nuclear Information System (INIS)

    Heparin, when added to citrated platelet-rich plasma (PRP), caused potentiation of platelet aggregation and the release reaction induced by the aggregating agents adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine. At low concentrations (4.7 x 10(-5) M) arachidonic acid failed to cause aggregation of platelets in citrated PRP. However, in the presence of heparin, the same concentration of arachidonic acid caused aggregation. Examination of PRP for the presence of thromboxane A2 (TxA2) by use of a bioassay revealed that heparin also stimulated release of TxA2. This finding indicated that platelets released more TxA2 when they were challenged by low concentrations of arachidonic acid in the presence of heparin than in its absence. Platelets were labeled with 3H-arachidonic acid and 14C-serotonin, and attempts were made to determine whether heparin stimulated the platelet release reaction first with subsequent increased production of TxA2, or alternatively, whether heparin stimulated TxA2 production first with subsequent enhancement of the release reaction. In view of the demonstrated simultaneous release of 14C-serotonin and 3H-arachidonic acid metabolites, it appeared that either release of 14C and 3H occurs concurrently or, even if one of these events is dependent on the other, both events take place in rapid succession. Timed sequential studies revealed that in the presence of arachidonic acid, the addition of heparin hastened the apparently simultaneous release of both 14C and 3H

  8. The combined impact of plant-derived dietary ingredients and acute stress on the intestinal arachidonic acid cascade in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Oxley, Anthony; Jolly, Cecile; Eide, Torunn; Jordal, Ann-Elise O; Svardal, Asbjørn; Olsen, Rolf-Erik

    2010-03-01

    A study was conducted to assess the effect of substituting high levels of dietary fish oil (FO) and fishmeal (FM) for vegetable oil (VO) and plant protein (PP) on the intestinal arachidonic acid (AA) cascade in the carnivorous fish species Atlantic salmon. Four diets were fed to salmon over a period of 12 months, including a control FMFO diet, with varying replacements of plant-derived ingredients: 80 % PP and 35 % VO; 40 % PP and 70 % VO; 80 % PP and 70 %VO. Subsequently, fish were examined pre- (0 h) and post- (1 h) acute stress for blood parameters and intestinal bioactive lipidic mediators of inflammation (prostaglandins). Plasma cortisol responses were greatest in the FMFO group, while 80 % PP and 70 % VO fish exhibited increased plasma chloride concentrations. The n-3:n-6 PUFA ratio in intestinal glycerophospholipids from 70 % VO groups significantly decreased in both proximal and distal regions due to elevated levels of 18 : 2n-6 and the elongation/desaturation products 20 : 2n-6 and 20 : 3n-6. Increases in n-6 PUFA were not concomitant with increased AA, although the AA:EPA ratio did vary significantly. The 40 % PP and 70 % VO diet produced the highest intestinal AA:EPA ratio proximally, which coincided with a trend in elevated levels of PGF2alpha, PGE2 and 6-keto-PGF1alpha in response to stress. PGE2 predominated over PGF2alpha and 6-keto-PGF1alpha (stable metabolite of PGI2) with comparable concentrations in both intestinal regions. Cyclo-oxygenase-2 (COX-2) mRNA expression was an order of magnitude higher in distal intestine, compared with proximal, and was significantly up-regulated following stress. Furthermore, the 80 % PP and 70 % VO diet significantly amplified proximal COX-2 induction post-stress. Results demonstrate that high replacements with plant-derived dietary ingredients can enhance COX-2 induction and synthesis of pro-inflammatory eicosanoids in the intestine of salmon in response to acute physiological stress. PMID:19943982

  9. Altered secretion of selected arachidonic acid metabolites during subclinical endometritis relative to estrous cycle stage and grade of fibrosis in mares.

    Science.gov (United States)

    Gajos, Katarzyna; Kozdrowski, Roland; Nowak, Marcin; Siemieniuch, Marta J

    2015-08-01

    Mares that fail to become pregnant after repeated breeding, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). Contact with infectious agents results in altered synthesis and secretion of inflammatory mediators, including cytokines and arachidonic acid metabolites, and disturbs endometrial functional balance. To address the hypothesis that SE affects the immune endocrine status of the equine endometrium, spontaneous secretion of prostaglandin E(2) (PGE(2)), prostaglandin F(2α) (PGF(2α)), 6-keto-PGF(1α )(a metabolite of prostacyclin I(2)), leukotriene B(4) (LTB(4)), and leukotriene C(4) (LTC(4)) was examined. In addition, secretion of these factors was examined relative to the grade of inflammation, fibrosis, and estrous cycle stage. Eighty-two warmblood mares, of known breeding history, were enrolled in this study. On the basis of histopathologic assessment, mares were classified as suffering from first-grade SE, second-grade SE, or being healthy. The grade of fibrosis and the infiltration of endometrial tissue with polymorphonuclear leukocytes were examined by routine hematoxylin-eosin staining. In mares suffering from SE, the secretion profiles of PGE(2), 6-keto-PGF(1α), LTB(4), and LTC(4) were changed compared to mares that did not suffer from endometritis. The secretion of PGE(2) and 6-keto-PGF1α was increased, whereas that of LTB(4) and LTC(4) was decreased. Secretion of 6-keto-PGF(1α) was increased in first- and second-grade SE (P < 0.01). The concentration of PGI(2) metabolite was increased only in inflamed endometrium, independently of the inflammation grade, but was not affected by fibrosis. Prostaglandin E(2) secretion was increased in second-grade SE (P < 0.05). The secretion of LTB(4) decreased in both first- and second-grade SE (P < 0.05), whereas secretion of LTC(4) was decreased only in second-grade SE (P < 0.05). Fibrosis did not change the secretion profile of PGE(2), PGF(2α), and 6

  10. Understanding the Mechanism of the Hydrogen Abstraction from Arachidonic Acid Catalyzed by the Human Enzyme 15-Lipoxygenase-2. A Quantum Mechanics/Molecular Mechanics Free Energy Simulation.

    Science.gov (United States)

    Suardíaz, Reynier; Jambrina, Pablo G; Masgrau, Laura; González-Lafont, Àngels; Rosta, Edina; Lluch, José M

    2016-04-12

    Lipoxygenases (LOXs) are a family of enzymes involved in the biosynthesis of several lipid mediators. In the case of human 15-LOX, the 15-LOX-1 and 15-LOX-2 isoforms show slightly different reaction regiospecificity and substrate specificity, indicating that substrate binding and recognition may be different, a fact that could be related to their different biological role. Here, we have used long molecular dynamics simulations, QM(DFT)/MM potential energy and free energy calculations (using the newly developed DHAM method), to investigate the binding mode of the arachidonic acid (AA) substrate into 15-LOX-2 and the rate-limiting hydrogen-abstraction reaction 15-LOX-2 catalyzes. Our results strongly indicate that hydrogen abstraction from C13 in 15-LOX-2 is only consistent with the "tail-first" orientation of AA, with its carboxylate group interacting with Arg429, and that only the pro-S H13 hydrogen will be abstracted (being the pro-R H13 and H10 too far from the acceptor oxygen atom). At the B3LYP/6-31G(d) level the potential and free energy barriers for the pro-S H13 abstraction of AA by 15-LOX-2 are 18.0 and 18.6 kcal/mol, respectively. To analyze the kinetics of the hydrogen abstraction process, we determined a Markov model corresponding to the unbiased simulations along the state-discretized reaction coordinate. The calculated rates based on the second largest eigenvalue of the Markov matrices agree well with experimental measurements, and also provide the means to directly determine the pre-exponential factor for the reaction by comparing with the free energy barrier height. Our calculated pre-exponential factor is close to the value of kBT/h. On the other hand, our results suggest that the spin inversion of the complete system (including the O2 molecule) that is required to happen at some point along the full process to lead to the final hydroperoxide product, is likely to take place during the hydrogen transfer, which is a proton coupled electron transfer

  11. Control of the growth of human breast cancer cells in culture by manipulation of arachidonate metabolism

    International Nuclear Information System (INIS)

    Arachidonate metabolites are important regulators of human breast cancer cells. Production of bioactive lipids are frequently initiated by the enzyme phospholipase A2 which releases arachidonic acid (AA) that is rapidly metabolized by cyclooxygenases (COX) or lipoxygenases (LO) to other highly potent lipids. In this study we screened a number of inhibitors which blocked specific pathways of AA metabolism for their antiproliferative activity on MCF-7 wild type and MCF-7 ADR drug resistant breast cancer cells. The toxicity of these inhibitors was further tested on human bone marrow cell proliferation. Inhibitors of LO pathways (specifically the 5-LO pathway) were most effective in blocking proliferation. Inhibitors of platelet activating factor, a byproduct of arachidonate release, were also effective antiproliferative agents. Curcumin, an inhibitor of both COX and LO pathways of eicosanoid metabolism, was 12-fold more effective in blocking proliferation of the MCF-7 ADRs cells compared to MCF-7 wild type (WT) cells. These inhibitors that effectively blocked the proliferation of breast cancer cells showed varying degrees of toxicity to cultures of human bone marrow cells. We observed greater toxicity to bone marrow cells with inhibitors that interfere with the utilization of AA in contrast to those which block utilization of its downstream metabolites. MK-591, MK-886, PCA-4248, and AA-861 blocked proliferation of breast cancer cells but showed no toxicity to bone marrow cells. These inhibitors were effective in blocking the proliferation of breast cancer cells and may be potentially useful in human breast cancer therapy

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

    OpenAIRE

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

    2011-01-01

    Over the past 50 years, increases in dietary n-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid, have been hypothesized to cause or exacerbate chronic inflammatory diseases. This study examines an individual’s innate capacity to synthesize n-6-long chain PUFAs (LC-PUFAs), with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes/metabolic syndrome. Compared to European Americans (EAm), African Americans (AfAm) exhibited marke...

  13. 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, ...

  14. Intestinal release and uptake of phenolic antioxidant diferulic acids

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Kroon, P A; Williamson, G;

    2001-01-01

    in oil. Our study also reveals that human and rat colonic microflora contain esterase activity able to release 5-5-, 8-O-4-, and 8-5-diferulic acids from model compounds and dietary cereal brans, hence providing a mechanism for release of dietary diferulates prior to absorption of the free acids...

  15. Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility.

    Science.gov (United States)

    Murase, Remi; Sato, Hiroyasu; Yamamoto, Kei; Ushida, Ayako; Nishito, Yasumasa; Ikeda, Kazutaka; Kobayashi, Tetsuyuki; Yamamoto, Toshinori; Taketomi, Yoshitaka; Murakami, Makoto

    2016-03-25

    Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizerin vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization. PMID:26828067

  16. [Therapeutic effects of larger doses of arachidonic acid added to DHA on social impairment and its relation to alterations of polyunsaturated fatty acids in individuals with autism spectrum disorders].

    Science.gov (United States)

    Yui, Kunio; Koshiba, Mamiko; Nakamura, Shun; Onishi, Masako

    2011-06-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and docosahexaenoic acid (DHA) may play key roles in brain network maturation. ARA plays an important role in signal transduction related to neuronal maturation. This study aims to evaluate the efficacy of supplementing with larger doses of ARA added to DHA in a double-blind, placebo-controlled 16-week trial. To confirm findings observed in the placebo-controlled trial, an additional 16-week open-label study was further conducted. To examine the relationship between the efficacy of the supplementation regimen and alterations in PUFAs levels, we examined plasma levels of PUFAs. We used the Social Responsiveness Scale (SRS) and the Aberrant Behavior Checklist-Community (ABC) to estimate psychotic symptoms. Repeated measures ANOVA revealed that this supplementation significantly improved SRS-measured communication as well as ABC-measured social withdrawal during the placebo-controlled trial. The treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: 0.87 vs. 0.44; social withdrawal: 0.88 vs. 0.54). At the end of the placebo-controlled trial, there was a significant difference in the change in plasma ARA levels from the baseline and a trend towards a significant difference in plasma ARA levels between the two groups. The open-label study was not powered to detect significant improvements in the outcome measures or significant differences in plasma ARA levels. The present clinical trials suggest that supplementation with larger ARA doses added to DHA improves social impairment in individuals with ASD via ARA-induced upregulation of neuronal functioning. PMID:21800702

  17. Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: a double-blind, placebo-controlled, randomized trial.

    Science.gov (United States)

    Yui, Kunio; Koshiba, Mamiko; Nakamura, Shun; Kobayashi, Yuji

    2012-04-01

    Autism spectrum disorders are a neurodevelopmental disorders with reduced cortical functional connectivity relating to social cognition. Polyunsaturated fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) may have key role in brain network maturation. In particularly, ARA is important in signal transduction related to neuronal maturation. Supplementation with larger ARA doses added to DHA may therefore mitigate social impairment. In a 16-week, double-blind, randomized, placebo-controlled trial, we evaluated the efficacy of supplementation with large doses of ARA added to DHA (n = 7) or placebo (n = 6) in 13 participants (mean age, 14.6 [SD, 5.9] years). To examine underlying mechanisms underlying the effect of our supplementation regimen, we examined plasma levels of antioxidants transferrin and superoxide dismutase, which are useful markers of signal transduction. The outcome measures were the Social Responsiveness Scale and the Aberrant Behavior Checklist-Community. Repeated-measures analysis of variance revealed that our supplementation regimen significantly improved Aberrant Behavior Checklist-Community-measured social withdrawal and Social Responsiveness Scale-measured communication. Treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: treatment groups, 0.87 vs, placebo, 0.44; social withdrawal: treatment groups, 0.88, vs placebo, 0.54). There was a significant difference in the change in plasma transferrin levels and a trend toward a significant difference in the change in plasma superoxide dismutase levels between the 2 groups. This preliminary study suggests that supplementation with larger ARA doses added to DHA improves impaired social interaction in individuals with autism spectrum disorder by up-regulating signal transduction. PMID:22370992

  18. 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.

  19. 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; Kristiansen, Karsten; Frøyland, Livar; Madsen, Lise

    2010-01-01

    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...

  20. Capture and release of acid-gasses with acid-gas binding organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Heldebrant, David J; Yonker, Clement R; Koech, Phillip K

    2015-03-17

    A system and method for acid-gas capture wherein organic acid-gas capture materials form hetero-atom analogs of alkyl-carbonate when contacted with an acid gas. These organic-acid gas capture materials include combinations of a weak acid and a base, or zwitterionic liquids. This invention allows for reversible acid-gas binding to these organic binding materials thus allowing for the capture and release of one or more acid gases. These acid-gas binding organic compounds can be regenerated to release the captured acid gasses and enable these organic acid-gas binding materials to be reused. This enables transport of the liquid capture compounds and the release of the acid gases from the organic liquid with significant energy savings compared to current aqueous systems.

  1. A rapid method for determining arachidonic:eicosapentaenoic acid ratios in whole blood lipids: correlation with erythrocyte membrane ratios and validation in a large Italian population of various ages and pathologies

    Directory of Open Access Journals (Sweden)

    Corsetto Paola

    2010-01-01

    Full Text Available Abstract Background Omega-3 and -6 polyunsaturated fatty acids (LCPUFA, are important for good health conditions. They are present in membrane phospholipids. The ratio of total n-6:n-3 LCPUFA and arachidonic acid:eicosapentaenoic acid (AA and EPA, should not exceed 5:1. Increased intake of n-6 and decreased consumption of n-3 has resulted in much higher, ca 10/15:1 ratio in RBC fatty acids with the possible appearance of a pathological "scenario". The determination of RBC phospholipid LCPUFA contents and ratios is the method of choice for assessing fatty acid status but it is labour intensive and time consuming. Aims of the study [i] To describe and validate a rapid method, suitable for large scale population studies, for total blood fatty acid assay; [ii] to verify a possible correlation between total n-6:n-3 ratio and AA:EPA ratios in RBC phospholipids and in whole-blood total lipids, [iii] to assess usefulness of these ratio as biomarkers of LCPUFA status. Methods 1 Healthy volunteers and patients with various pathologies were recruited. 2 Fatty acid analyses by GC of methyl esters from directly derivatized whole blood total lipids and from RBC phospholipids were performed on fasting blood samples from 1432 subjects categorised according to their age, sex and any existing pathologies. AA:EPA ratio and the total n-6:n-3 ratio were determined. Results AA:EPA ratio is a more sensitive and reliable index for determining changes in total blood fatty acid and it is correlated with the ratio derived from extracted RBC phospholipids. Conclusions The described AA:EPA ratio is a simple, rapid and reliable method for determining n-3 fatty acid status.

  2. Novel Caffeic Acid Nanocarrier: Production, Characterization, and Release Modeling

    Directory of Open Access Journals (Sweden)

    Milad Fathi

    2013-01-01

    Full Text Available This paper deals with the development of novel nanocarriers using layer by layer carbohydrate coating of caffeic acid loaded solid lipid nanoparticles (SLNs to improve stability and colon delivery of the poorly water-soluble caffeic acid. Three biopolymers (chitosan, alginate, and pectin in different concentrations (0.1, 0.25, and 0.5% were electrostatically coated over the SLN surface. The size and zeta potential of produced nanocarriers were measured using photon correlation spectroscopy. Mathematical models (i.e., zero-order, first-order, Higuchi, Ritger-Peppas, reciprocal powered time, Weibull, and quadratic models were used to describe the release and kinetic modeling in gastrointestinal solution (GIS. Also, antioxidant activity of caffeic acid during the release in GIS was investigated using DPPH and reducing activity methods. The prepared treatments coated by alginate-chitosan as well as pectin-chitosan coated SLN at the concentration of 0.1% showed nanosized bead; the latter efficiently retarded the release of caffeic acid in gastric media up to 2.5 times higher than that of SLN. Zeta potential values of coated samples were found to significantly increase in comparison to SLN indicating the higher stability of produced nanocarriers. Antioxidant activity of caffeic acid after gastric release did not result in the same trend as observed for caffeic acid release from different treatments; however, in line with less caffeic acid release in the intestine solution by the effect of coating, lower antioxidant activity was determined at the end stage of the experiment.

  3. Release of selected amino acids from zinc carriers.

    Science.gov (United States)

    Dyja, Renata; Dolińska, Barbara; Ryszka, Florian

    2016-06-01

    The paper deals with the results of an investigation of the release of selected amino acids (histidine, tryptophan, tyrosine) from model suspensions prepared by co-precipitation with zinc chloride. It has been proven that the influence of the Zn(II)/amino acid molar ratio on dissolution profiles of the tested amino acids and dissolution half-life (t1/2) of histidine or tryptophan is significant. The amount of amino acid in the dispersed phase (supporting dose) is a determinant of the amino acid release profile. There is a minimal supporting dose (30.0 μmol of histidine or 17.4 μmol of tryptophan) that provides release of similar amounts of amino acid (4.1-4.6 μmol of histidine or 8.7-9.9 μmol of tryptophan) after the same time intervals. The tyrosine release profiles follow first order kinetics since the supporting dose (0.9-11.2 μmol) is limited by the tyrosine low solubility in water. PMID:27279069

  4. Acidic preparations of platelet concentrates release bone morphogenetic protein-2.

    OpenAIRE

    Wahlström, Ola; Linder, Cecilia; Kalén, Anders; Magnusson, Per

    2008-01-01

    BACKGROUND AND PURPOSE: Growth factors released from platelets have potent effects on fracture and wound healing. The acidic tide of wound healing, i.e. the pH within wounds and fractures, changes from acidic pH to neutral and alkaline pH as the healing process progresses. We investigated the influence of pH on lysed platelet concentrates regarding the release of growth factors. MATERIAL AND METHODS: Platelet concentrates free of leukocyte components were lysed and incubated in buffers with p...

  5. Acid Release from an Acid Sulfate Soil Sample Under Successive Extractions with Different Extractants

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    An acid sulfate soil sample was successively extracted with deionized water, 1 mol L-1 KCI and 0.000 5 mol L-1 Ca(OH)2 solutions. The results showed that only very small amounts of acidity were extracted by deionized water, possibly through slow jarosite hydrolysis. Acid release through jarosite hydrolysis was greatly enhanced by Ca(OH)2 extraction at the expense of the added OH- being neutralized by the acid released. Successive extraction of the sample with KCI removed the largest amounts of acidity from the sample. However, it is likely that the major form of acidity released by KC1 extraction was exchangeable acidity. The results also show the occurrence of low or non charged A1 and Fe species in water and Ca(OH)2 extracts after first a few extractions. It appears that such a phenomenon was related to a decreasing EC value with increasing number of extractions.

  6. POLARIZED RELEASE OF LIPID MEDIATORS DERIVED FROM PHOSPHOLIPASE A2 ACTIVITY IN A HUMAN BRONCHIAL CELL LINE

    Science.gov (United States)

    The release of arachidonic acid (AA) and platelet activating factory (PAF) from airway epithelial cells may be an important mediating factor in lung physiological and inflammatory processes. The type of lung response may be determined by the directional release of AA and PAF. We ...

  7. Mechanism of drug release from poly(L-lactic acid) matrix containing acidic or neutral drugs.

    Science.gov (United States)

    Miyajima, M; Koshika, A; Okada, J; Ikeda, M

    1999-08-01

    The release profiles of acidic and neutral drugs from poly(L-lactic acid) [P(L)LA] matrices were investigated to reveal their release mechanism. Cylindrical matrices (rods; 10 mmx1 mm diameter) were prepared by the heat compression method. The acidic and neutral drugs investigated were dissolved in the P(L)LA rods. It was found that the release profiles consisted of two sequential stages. At the first release stage, P(L)LA remained in an amorphous state and the drugs diffused through the hydrated matrices. At the second release stage, P(L)LA transformed to a semicrystalline state and the drugs diffused through water-filled micropores developed by polymer crystallization. In addition, the drugs were also found to precipitate out as crystals in the rods, resulting in a transformation of the rods into drug-dispersed matrices. On the basis of these findings, we derived a modified diffusion equation for the drug release at the second stage. This equation showed good fits to the release profiles of these drugs. Furthermore, the availability of the derived equation was supported by the acceleration in the fractional drug release rate noted both with decreases in the drug content in the rod and increases in the pH of the medium. PMID:10425326

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

    International Nuclear Information System (INIS)

    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

  9. Acid rain draft study released: No environmental emergency found

    International Nuclear Information System (INIS)

    This article discusses the findings released in the draft study of the National Acid Precipitation Assessment Program (NAPAP). Some areas where acidic deposition and related air pollution is evident include 10 percent of eastern lakes and streams, visibility reduction throughout the eastern US and large metropolitan areas of the West, erosion and corrosion damage to stone and metal structures and cultural resources, and a reduction in cold tolerance of red spruce trees at high elevations. Human health effects have not been clearly demonstrated. The report tied sulfur dioxide emissions to regions of high acidic deposition. The problem is characterized as not an environmental emergency but a long term problem that should be addressed with minimum impact on other environmental goals and with efficient use of the nations economic and energy resources

  10. Ion-beam-mutation breeding of an arachidonic acid biosynthesis microorganism and its industrial fermentation control%微生物油脂花生四烯酸产生菌离子束诱变和发酵调控

    Institute of Scientific and Technical Information of China (English)

    余增亮; 王纪; 袁成凌; 黄青; 冯慧云; 贡国鸿; 郑之明; 姚建铭

    2012-01-01

    某些微生物是高质量油脂的生产者.微生物油脂不仅有益健康,而且是生物柴油潜在的油脂来源.中国是个油脂资源缺乏的国家,开发微生物源油脂具有重要的意义.本文以产油微生物——高山被孢霉菌为出发菌,以单细胞油脂多不饱和脂肪酸产率为筛选目标,采用二步离子束诱变-筛选的策略,获得了高产菌株.研究了高产菌株的营养需求,创建了重复利用提油后的残体(菌粕)合成微生物油脂的技术.针对丝状真菌高密度发酵的传能和传质问题,研制了6×50和4×200m3大容量专用反应器组,单位发酵容积生物量达38.2g/L(发酵液)、油脂20.67g/L.其中具有重要生理活性的花生四烯酸产率最高达9.89 g/L,平均为8.97g/L.花生四烯酸提取和精炼后的残油转化为生物柴油,主要指标达到国家生物柴油标准.%Some microorganisms in nature produce high-quality oils. These oils provide nutritional benefits to human health, and can be potential sources of biodiesel. Developing microorganism-derived oils, also known as single-cell oils, is particularly important for China because of the shortage of oil resources. We have bred a high-yielding, polyunsaturated fatty acids (PUFCs)-producing strain from the fungi Mortierelia alpine by using a two-step strategy of ion-beam-mutation breeding and PUFCs productivity screening. We further studied the nutritional requirements of this new strain, and developed a technique that recycles the fungi residues, after oil extraction, into fermentation substrates. A biomass of 38.2 g/L, 20.67 g/L of which were oils, was reached in the 6x50 m3 and 4x200 m3 high-capacity reactors, designed for mycelial fungus fermentation at high-density, with optimized energy and mass transmission efficiency. Among the oils, the content of the physiologically active arachidonic acid reached 9.89 g/L at the highest level and 8.97 g/L on average. Residual oils, after arachidonic acid

  11. THE EFFECT OF ACIDIC EXCIPIENTS ON THE RELEASE OF WEAKLY BASIC DRUGS FROM THE PROGRAMMED RELEASE MEGALOPOROUS SYSTEM

    NARCIS (Netherlands)

    VANDERVEEN, C; BUITENDIJK, H; LERK, CF

    1991-01-01

    Weakly basic drugs such as ketanserin and mianserin exhibit strongly pH-dependent solubilities. Incorporated in the programmed release megaloporous system, these drugs showed pH-dependent release profiles. The strongly inhibited release rates in neutral media compared to acidic media, could be raise

  12. PREPARATION OF SUSTAINED-RELEASE TIABROFENIC ACID BEADS

    OpenAIRE

    Y. OZSOY, A. ARAMAN, A. YILDIZ, D. SENSOY, A. BAYTOKOVA,

    2015-01-01

    Tiaprofenic acid (TA), has analgesic, anti-inflammatory and antipyreticproperties; it is an inhibitor of prostaglandin synthetase. The usual oral dose bymouth is 600 mg daily; this may be given in 2 or 3 divided doses or once daily as a sustained-release preparation. TA is readily absorbed from the gastrointestinal tract. It has a short half-life of about 2 hours.Sodium alginate is a natural, biodegradable and biocornpatible polymer usedas suspending and gelling agent in pharmaceutical techno...

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

    Directory of Open Access Journals (Sweden)

    J. O. Woo

    2014-01-01

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

  14. PLA2 - a major regulator of volume-sensitive taurine release in NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Lambert, I. H.

    2006-01-01

    -lipoxygenase (5-LO) system is prevented by the 5-LO inhibitor ETH 615-139 and is reduced under hypertonic conditions. Exposure to the amphiphilic bee venom peptide melittin, which has no effect on the kinetic properties of PLA2 but promotes substrate replenishment, induces release of arachidonic acid and...

  15. Inhibition of Aspergillus growth and aflatoxin release by derivatives of benzoic acid.

    OpenAIRE

    Chipley, J. R.; Uraih, N

    1980-01-01

    A study was conducted to determine the effects of o-nitrobenzoate, p-aminobenzoate, benzocaine (ethyl aminobenzoate), ethyl benzoate, methyl benzoate, salicylic acid (o-hydroxybenzoate), trans-cinnamic acid (beta-phenylacrylic acid), trans-cinnamaldehyde (3-phenylpropenal), ferulic acid (p-hydroxy-3-methoxycinnamic acid), aspirin (o-acetoxy benzoic acid), and anthranilic acid (o-aminobenzoic acid) upon growth and aflatoxin release in Aspergillus flavus NRRL 3145 and A. parasiticus NRRL 3240. ...

  16. Dexamethasone blocks arachidonate biosynthesis in isolated hepatocytes and cultured hepatoma cells

    International Nuclear Information System (INIS)

    The effect of dexamethasone on the incorporation and conversion of [1-14C]eicosa-8,11,14-trienoic acid to arachidonic acid in isolated hepatocytes and in hepatoma tissue culture (HTC) cells was studied. In both kinds of cells, no changes in the exogenous acid incorporation were found when the hormone was added to the incubation media at 0.1 or 0.2 mM concentration, while the biosynthesis of arachidonic acid was significantly depressed. The effect on the biosynthesis was faster in isolated normal liver cells (60 min) than in tumoral cells (120 min) and reached an inhibition of ca. 50% after 3 hr of treatment. The addition of cycloheximide (10(-6) M) also caused a marked decrease in the biosynthesis of this polyunsaturated fatty acid, but when dexamethasone was added to the media simultaneously with cycloheximide, a synergistic action was not observed. The results obtained show that protein synthesis would be involved in the modulation of the biosynthesis of arachidonic acid by glucocorticoids. The changes in the delta 5 desaturation of labeled 20:3 omega 6 to arachidonic acid correlated with changes in the fatty acid composition in isolated cells

  17. Membrane sialic acid influences basophil histamine release by interfering with calcium dependence

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Skov, P S;

    1987-01-01

    The influence of the cell membrane content of sialic acid on basophil histamine release was examined in vitro in allergic patients and normal controls. Enzymatical removal of sialic acid enhanced histamine release induced by allergen and anti-IgE, whereas an increase in membrane sialic acid content...

  18. Metal release from fly ash upon leaching with sulfuric acid or acid mine drainage

    International Nuclear Information System (INIS)

    Generation of electricity by coal-fired power plants produces large quantities of bottom ash and fly ash. New power plants commonly use fluidized bed combustion (FBC) boilers, which create ashes with high neutralization potential (NP). These ashes, due to their alkaline nature, are often used in surface mine reclamation to neutralize acidity and reduce hydraulic conductivity of disturbed overburdens. Conventional fly ashes from older power plants exhibit a range of pH and NP, with some ashes having neutral or acidic pH and low NP values, and may not be good candidates for supplying alkalinity in reclamation projects. In this study, the authors used two acidic solutions to leach a low NP fly ash (LNP ash) and two FBC ashes (FBC1 and FBC2). After passing 78 pore volumes of sulfuric acid and 129 pore volumes of acid mine drainage (AMD) through these ash materials several trace elements were found at high levels in the leachates. LNP fly ash leachates had high arsenic and selenium concentrations with sulfuric acid leaching, but showed low arsenic and selenium concentrations after leaching with AMD. Leaching with AMD caused the iron and aluminum inherent in AMD to complex these elements and make them unavailable for leaching. Lead, cadmium, and barium concentrations in fly ash leachates were not high enough to cause water pollution problems with either leaching solution. For both leaching solutions, manganese was released from LNP ash at a constant level, FBC1 ash did not release manganese, and FBC2 ash released manganese only after the NP had been exhausted by >60 pore volumes of leaching

  19. Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

    1995-01-01

    Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

  20. Release of brain amino acids during hyposmolar stress and energy deprivation.

    Science.gov (United States)

    Haugstad, T S; Langmoen, I A

    1996-04-01

    The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or energy deprivation was measured by high-performance liquid chromatography. Exposing the slices to hyposmotic stress by lowering extracellular NaCl caused a 10-fold release of taurine (p alanine release (p isoelectric point) and hydropathy indexes. Energy deprivation increased the permissivity in the following order: acidic > neutral > basic. Among neutral amino acids, permissivity increased with increasing hydrophobicity. These results indicate that the mechanisms of amino acid release are different during cerebral ischemia and hyposmotic stress. PMID:8829565

  1. Simultaneous Intercalation of 1-Naphthylacetic Acid and Indole-3-butyric Acid into Layered Double Hydroxides and Controlled Release Properties

    OpenAIRE

    Shifeng Li; Yanming Shen; Min Xiao; Dongbin Liu; Lihui Fan; Zhigang Zhang

    2014-01-01

    Controlled release formulations have been shown to have potential in overcoming the drawbacks of conventional plant growth regulators formulations. A controlled-release formulation of 1-naphthylacetic acid (NAA) and indole-3-butyric acid (IBA) simultaneous intercalated MgAl-layered double hydroxides (LDHs) was prepared. The synthetic nanohybrid material was characterized by various techniques, and release kinetics was studied. NAA and IBA anions located in the gallery of MgAl-LDHs with bilaye...

  2. Influence of Organic Acids on Diltiazem HCl Release Kinetics from Hydroxypropyl Methyl Cellulose Matrix Tablets.

    Science.gov (United States)

    Sateesha, Sb; Rajamma, Aj; Narode, Mk; Vyas, Bd

    2010-07-01

    The matrix tablets of diltiazem hydrochloride were prepared by direct compression using hydroxypropyl methyl cellulose (HPMC) and various amounts (2.5%, 5.0%, 10% and 20%) of citric acid, malic acid and succinic acid. The characterization of physical mixture of drug and organic acids was performed by Infra-red spectroscopy. An organic acid was incorporated to set up a system bringing about gradual release of this drug. The influence of organic acids on the release rate were described by the Peppas equation: M (t) /M(∞) = Kt (n) and Higuchi's equation: Q (t) = K(1)t(1/2). The addition of organic acids and the pH value of medium could notably influence the dissolution behavior and mechanism of drug-release from matrices. Increasing amounts of organic acid produced an increase in drug release rate, which showed a good linear relationship between contents of organic acid and drug accumulate release (%) in phosphate buffer, pH 7.4. The drug release increased significantly (P < 0.05) with use of succinic acid in tablet formulation. Increasing amounts of succinic acid above 10% produced decreasing values of n and increasing values of k, in a linear relationship, which indicated there was a burst release of drug from the matrix. Optimized formulations are found to be stable upon 3-month study. PMID:21042476

  3. Phosphorus release from phosphate rock and iron phosphate by low-molecular-weight organic acids

    Institute of Scientific and Technical Information of China (English)

    XU Ren-kou; ZHU Yong-guan; David Chittleborough

    2004-01-01

    Low-molecular-weight(LMW) organic acids widely exist in soils, particularly in the rhizosphere. A series of batch experiments were carried out to investigate the phosphorus release from rock phosphate and iron phosphate by Iow-molecular-weight organic acids.Results showed that citric acid had the highest capacity to solubilize P from both rock and iron phosphate. P solubilization from rock phosphate and iron phosphate resulted in net proton consumption. P release from rock phosphate was positively correlated with the pKa values. P release from iron phosphate was positively correlated with Fe-organic acid stability constants except for aromatic acids, but was not correlated with PKa. Increase in the concentrations of organic acids enhanced P solubilization from both rock and iron phosphate almost linearrly. Addition of phenolic compounds further increased the P release from iron phosphate. Initial solution pH had much more substantial effect on P release from rock phosphate than from iron phosphate.

  4. Novel amino acids: synthesis of furoxan and sydnonimine containing amino acids and peptides as potential nitric oxide releasing motifs.

    Science.gov (United States)

    Nortcliffe, Andrew; Botting, Nigel P; O'Hagan, David

    2013-07-28

    The incorporation of furoxan and sydnonimine ring systems into amino acid side chains is demonstrated with the preparation of four novel amino acids which carry these nitric oxide-releasing motifs. N-((4-Nitrophenoxy)carbonyl)-3-phenylsydnonimine 9 and bis(phenylsulfonyl)furoxan 10 are the key intermediates for introducing the heterocycle side chains onto appropriate amine and alcohol functionalities respectively. Furoxan 5 and 7 both displayed NO release based on determination of nitrite production. Orthogonal amino acid protecting group strategies were deployed to demonstrate that the amino acids could be incorporated into peptide frameworks. By way of demonstration the amino acids were placed centrally into several tripeptide motifs. Griess test assays showed that these amino acids released NO in the presence of γ-glutathione (GST). PMID:23753002

  5. Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo.

    OpenAIRE

    Connick, J. H.; Stone, T. W.

    1988-01-01

    1. The effect of quinolinic acid, N-methyl-D,L-aspartate (NMDLA) and kainate on the release of endogenous and exogenous amino acids from the rat cerebral cortex in vitro and in vivo was studied. 2. Neither quinolinic acid nor NMDLA had any effect on the basal or potassium-evoked release of [3H]-D-aspartate from slices of rat cerebral cortex either in the presence or absence of magnesium. Kainic acid failed to modify the basal efflux of [3H]-D-aspartate but significantly inhibited (by 34.4% +/...

  6. Simultaneous Intercalation of 1-Naphthylacetic Acid and Indole-3-butyric Acid into Layered Double Hydroxides and Controlled Release Properties

    Directory of Open Access Journals (Sweden)

    Shifeng Li

    2014-01-01

    Full Text Available Controlled release formulations have been shown to have potential in overcoming the drawbacks of conventional plant growth regulators formulations. A controlled-release formulation of 1-naphthylacetic acid (NAA and indole-3-butyric acid (IBA simultaneous intercalated MgAl-layered double hydroxides (LDHs was prepared. The synthetic nanohybrid material was characterized by various techniques, and release kinetics was studied. NAA and IBA anions located in the gallery of MgAl-LDHs with bilayer arrangement, and the nanohybrids particles were of typical plate-like shape with the lateral size of 50–100 nm. The results revealed that NAA and IBA have been intercalated into the interlayer spaces of MgAl-LDHs. The release of NAA and IBA fits pseudo-second-order model and is dependent on temperature, pH value, and release medium. The nanohybrids of NAA and IBA simultaneously intercalated in LDHs possessed good controlled release properties.

  7. Inhibitors of the cytochrome P-450 enzymes block the secretagogue-induced release of corticotropin in mouse pituitary tumor cells.

    OpenAIRE

    Luini, A G; Axelrod, J

    1985-01-01

    A mouse pituitary tumor cell line (AtT-20) releases corticotropin (ACTH) in response to a number of secretagogues, including corticotropin-releasing factor (CRF), beta-adrenergic agents, N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2 cAMP), and potassium. The stimulation of ACTH secretion induced by the secretagogues can be blocked by inhibitors of the enzymes that generate (phospholipase A2) and metabolize (lipoxygenase and epoxygenase) arachidonic acid. The phospholipase A2 block...

  8. Oxidation of esterified arachidonate by rat liver microsomes

    International Nuclear Information System (INIS)

    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-14C) was incorporated into rat liver microsomes and NADPH-supported peroxidation was carried out at 370C 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 A2 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 Fe3+ and since product formation is unaffected in the presence of carbon monoxide

  9. Wheat-Exuded Organic Acids Influence Zinc Release from Calcareous Soils

    Institute of Scientific and Technical Information of China (English)

    M. A. MAQSOOD; S. HUSSAIN; T. AZIZ; M. ASHRAF

    2011-01-01

    Rhizosphere drives plant uptake of sparingly soluble soil zinc (Zn).An investigation with three experiments was conducted to study organic acid exudation by two contrasting wheat genotypes (Sehar-06 and Vatan),Zn fractious in 10 different calcareous soils from Punjab,Pakistan,and release of different soil Zn fractions by organic acids.The two genotypes differed significantly in biomass production and Zn accumulation under deficient and optimum Zn levels in nutrient solution.At a deficient Zn level,Sehar-06 released more maleic acid in the rhizosphere than Vatan.Ten soils used in the present study had very different physicochemical properties; their total Zn and Zn distribution among different fractions varied significantly.Zinc release behaviour was determined by extracting the soils with 0.005 mol L-1 citric acid or maleic acid.The parabolic diffusion model best described Zn release as a function of time.Parabolic diffusion model fitting indicated more maleic acid-driven than citric acid-driven soil Zn mobility from different fractions.Cumulative Zn release in six consecutive extractions during 24 h ranged from 1.85 to 13.58 mg kg-1 using maleic acid and from 0.37 to 11.84 mg kg-1 using citric acid.In the selected calcareous soils,the results of stepwise linear regression indicated significant release of Fe-Mn oxide-bounded soil Zn by maleic acid and its availability to the Zn-efficient genotype.Hence,release of maleic acid by plants roots played an important role in phytoavailability of Zn from calcareous soils.

  10. pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Background and purpose of the study: Propranolol HCl, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Methods: Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15 % were added to the matrices prepared by hydroxypropyl methylcellulose (HPMC and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time (MDT as well as similarity factor (¦2 were calculated for all formulations. Results and discussion: It was found that incorporation of 5 and 10 % tartaric acid in tablet formulations with 30 % HPMC resulted in a suitable pH-independent release profiles with significant higher ¦2 values (89.9 and 87.6 respectively compared to acid free tablet (58.03. The other two acids did not show the desirable effects. It seems that lower pKa of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles.

  11. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein–Coupled Bile Acid Receptors

    OpenAIRE

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E; Glass, Leslie L; Schoonjans, Kristina; Holst, Jens J.; Gribble, Fiona M.; Reimann, Frank

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from t...

  12. Radiation-induced increase in the release of amino acids by isolated, perfused skeletal muscle

    International Nuclear Information System (INIS)

    Local exposure of the hindquarter of the rat to 15Gy of gamma-radiation resulted, 4-6h after irradiation, in increased release of amino acids by the isolated, perfused hindquarter preparation, 70% of which is skeletal muscle. This increase in release involves not only alanine and glutamine, but also those amino acids not metabolized by muscle and, therefore, released in proportion to their occurrence in muscle proteins. Because metabolic parameters and content of energy-rich phosphate compounds in muscle remain unchanged, it is unlikely that general cellular damage is the underlying cause of the radiation-induced increase in amino acid release. The findings strongly favour the hypothesis that increased availability of amino acids results from enhanced protein break-down in skeletal muscle which has its onset shortly after irradiation. This radiation-induced disturbance in protein metabolism might be one of the pathogenetic factors in the aetiology of radiation myopathy. (author)

  13. Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation

    OpenAIRE

    Basselin, Mireille; Kim, Hyung-Wook; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Robert C. Murphy; Farias, Santiago E.

    2010-01-01

    Neuroinflammation, caused by 6 days of intracerebroventricular infusion of a low dose of lipopolysaccharide (LPS; 0.5 ng/h), stimulates brain arachidonic acid (AA) metabolism in rats, but 6 weeks of lithium pretreatment reduces this effect. To further understand this action of lithium, we measured concentrations of eicosanoids and docosanoids generated from AA and docosahexaenoic acid (DHA), respectively, in high-energy microwaved rat brain using LC/MS/MS and two doses of LPS. In rats fed a l...

  14. The effect of carbohydrate and fat variation in euenergetic diets on postabsorptive free fatty acid release

    NARCIS (Netherlands)

    Bisschop, PH; Ackermans, MT; Endert, E; Ruiter, AFC; Meijer, AJ; Kuipers, F; Sauerwein, HP; Romijn, JA

    2002-01-01

    Diet composition and energy content modulate free fatty acid (FFA) release. The aim of this study was to evaluate the dose-response effects of euenergetic variations in dietary carbohydrate and fat content on postabsorptive FFA release. The rate of appearance (R-a) of palmitate was measured by infus

  15. Does gastric acid release plasma somatostatin in man?

    OpenAIRE

    Lucey, M.R.; Wass, J A; Fairclough, P D; O'Hare, M; Kwasowski, P; Penman, E; Webb, J.; Rees, L H

    1984-01-01

    Food and insulin hypoglycaemia raise plasma concentrations of somatostatin. Both also stimulate gastric acid secretion but it is not clear whether gastric acid itself has any effect on somatostatin secretion. We, therefore, studied the effect on plasma concentrations of somatostatin of infusion of 0.1 N HC1 into the stomach and duodenum of healthy subjects. Plasma somatostatin did not rise with a small dose of HC1 given intragastrically (15 mmol) or intraduodenally (4 mmol). After an intraduo...

  16. Acrolein stimulates eicosanoid release from bovine airway epithelial cells

    International Nuclear Information System (INIS)

    Injury to the airway mucosa after exposure to environmental irritants is associated with pulmonary inflammation and bronchial hyperresponsiveness. To better understand the relationships between mediator release and airway epithelial cell injury during irritant exposures, we studied the effects of acrolein, a low-molecular-weight aldehyde found in cigarette smoke, on arachidonic acid metabolism in cultured bovine tracheal epithelial cells. Confluent airway epithelial cell monolayers, prelabeled with [3H]arachidonic acid, released significant levels of 3H activity when exposed (20 min) to 100 microM acrolein. [3H]arachidonic acid products were resolved using reverse-phase high-performance liquid chromatography. Under control conditions the released 3H activity coeluted predominantly with the cyclooxygenase product, prostaglandin (PG) E2. After exposure to acrolein, significant peaks in 3H activity coeluted with the lipoxygenase products 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE, as well as with PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. Dose-response relationships for acrolein-induced release of immunoreactive PGF2 alpha and PGE2 from unlabeled epithelial monolayers demonstrated 30 microM acrolein as the threshold dose, with 100 microM acrolein inducing nearly a fivefold increase in both PGF2 alpha and PGE2. Cellular viability after exposure to 100 microM acrolein, determined by released lactate dehydrogenase activity, was not affected until exposure periods were greater than or equal to 2 h. These results implicate the airway epithelial cell as a possible source of eicosanoids after exposure to acrolein

  17. Recognition and Release of Nalidixic Acid Using Uniformly Sized -Imprinted Nanospheres: Methacrylic Acid to Methyl Methacrylate Different Mole Ratios

    Directory of Open Access Journals (Sweden)

    Mehdi Forouzani

    2013-01-01

    Full Text Available In the presence of imprinting molecules of Nalidixic acid, uniformly sized molecularly imprinted polymers (MIPs in nanometer range were synthesized. The MIPs were successfully prepared by precipitation polymerization using methacrylic acid (MAA and methyl methacrylate (MMA as functional monomers at different mole ratios. The effect of combination of MAA-to-MMA on the morphology, binding, recognition and release behaviors of the final particles were studied. The produced polymers were characterized by differential scanning calorimetry and their morphology was precisely examined by scanning electron microscopy. We obtained very uniform imprinted nanospheres with diameter of 120- 180 nm. Among the MIP nanospheres the MIPs using combination of MAA and MMA showed nanospheres with lowest mean diameter (120 nm and the highest selectivity factor (9.7. The adsorption properties of Nalidixic acid in acetonitrile for imprinted nanospheres were evaluated by equilibrium rebinding experiments. Results from binding experiments proved that MIPs exhibit specific affinity to Nalidixic acid in contrast to control polymers and this performance was affected by pH of loading solution and. Moreover, release experiments showed the controlled release of Nalidixic acid in longtime period. The loaded Nalidixic acid was released from the imprinted nanospheres within the 140 h.

  18. Preparation of coated valproic acid and sodium valproate sustained-release matrix tablets

    Directory of Open Access Journals (Sweden)

    Phaechamud T

    2010-01-01

    Full Text Available The aim of this research was to investigate the technique for preparation of coated valproic acid and sodium valproate sustained-release matrix tablets. Different diluents were tested and selected as the effective absorbent for oily valproic acid. Effect of the amount of absorbent and hydroxypropylmethylcellulose on drug release from valproic acid-sodium valproate matrix tablets prepared with wet granulation technique was evaluated in pH change system. Colloidal silicon dioxide effectively adsorbed liquid valproic acid during wet granulation and granule preparation. The amounts of colloidal silicon dioxide and hydroxypropylmethylcellulose employed in tablet formulations affected drug release from the tablets. The drug release was prominently sustained for over 12 h using hydroxypropylmethylcellulose-based hydrophilic matrix system. The mechanism of drug release through the matrix polymer was a diffusion control. The drug release profile of the developed matrix tablet was similar to Depakine Chrono; , providing the values of similarity factor (f2 and difference factor (f1 of 85.56 and 2.37, respectively. Eudragit; L 30 D-55 was used as effective subcoating material for core matrix tablets before over coating with hydroxypropylmethylcellulose film with organic base solvent. Drug release profile of coated matrix tablet was almost similar to that of Depakine Chrono; .

  19. Digestion of thyroglobulin with purified thyroid lysosomes: preferential release of iodoamino acids

    International Nuclear Information System (INIS)

    [131I]Thyroglobulin [( 131I]Tg), prepared by either enzymatic iodination of human goiter Tg in vitro or isolation from the thyroids of rats previously injected with 131I, was digested with a solubilized enzyme mixture prepared from purified hog thyroid lysosomes. The digestion was performed at 37 C for 24 h under nitrogen at pH 5.0 in the presence of 4 mM dithiothreitol. Under these conditions the release of free [131I] iodoamino acids (MIT, DIT, T4, and T3) was quantitatively very similar to that observed with a standard pronase digestion procedure. To determine whether other amino acids in Tg were released as quantitatively as the iodoamino acids, free amino acids in the lysosomal digest were measured, and total free amino acid release was compared with a similar analysis performed after digestion of [131I]Tg with 6 N HCl. Total amino acid release was much less complete than iodoamino acid release, indicating preferential release of iodoamino acids from Tg by lysosomal digestion. Analysis of the lysosomal digest by HPLC on a size exclusion column indicated that Tg was degraded to peptides with a mol wt less than 4000. Assuming that the in vitro lysosomal digestion system represents a valid model for the physiological proteolytic system that degrades Tg, the results of the present study suggest that a substantial portion of the Tg in the thyroid is not degraded to free amino acids and that peptide fragments of Tg are normally present in the thyroid. In such a case, the fate and possible physiological activity of these fragments require further elucidation

  20. Sandwich Structure-like Meshes Fabricated via Electrospinning for Controllable Release of Zoledronic Acid

    Institute of Scientific and Technical Information of China (English)

    LU Jian; LIU Jian-guo; SONG Xiao-feng; CHEN Xue-si; WU Xiao-dong

    2011-01-01

    Novel sandwich structure-like nanofiber multilayered meshes were fabricated via electrospinning. The purpose of the present work was to control zoledronic acid release via the novel structure of sandwich structure-like meshes. The in vitro release experiments reveal that the drug release speed and initial burst release were controllable by adjusting the thicknesses of electrospun barrier mesh and drug-loaded mesh. Compared with those of other drug delivery systems, the main advantages of the sandwich structure-like fiber meshes are facile preparation conditions and the generality for hydrophobic and hydrophilic pharmaceuticals.

  1. Effect of Oxalic Acid on Potassium Release from Typical Chinese Soils and Minerals

    Institute of Scientific and Technical Information of China (English)

    TU Shu-Xin; GUO Zhi-Fen; SUN Jin-He

    2007-01-01

    Oxalic acid plays an important role in improving the bioavailability of soil nutrients. Batch experiments were employed to examine the influences of oxalic acid on extraction and release kinetics of potassium (K) from soils and minerals along with the adsorption and desorption of soil K+. The soils and minerals used were three typical Chinese soils, black soil (Mollisol), red soil (Ultisol), and calcareous alluvial soil (Entisol), and four K-bearing minerals, biotite, phlogopite, muscovite, and microcline. The results showed that soil K extracted using 0.2 mol L-1 oxalic acid was similar to that using 1 mol L-1 boiling HNO3. The relation between K release (y) and concentrations of oxalic acid (c) could be best described logarithmically as y=a+blogc, while the best-fit kinetic equation of K release was y=a +b√t, where a and b are the constants and t is the elapsed time. The K release for minerals was ranked as biotite> phlogopite>> muscovite> microcline and for soils it was in the order: black soil> calcareous alluvial soil> red soil. An oxalic acid solution with low pH was able to release more K from weathered minerals and alkaline soils. Oxalic acid decreased the soil K+ adsorption and increased the soil K+ desorption, the effect of which tended to be greater at lower solution pH, especially in the red soil.

  2. Development of paradigm for the study of amino acid neurotransmitter release in human autopsy brain samples

    International Nuclear Information System (INIS)

    Full text: This study attempted to establish a release protocol to characterize both the vesicular and cytoplasmic components of amino acid transmitter release in human synaptosomes. Experiments with rat synaptosomes showed that, with depolarizing concentrations of K+ ions, vesicular release could be successfully differentiated from cytoplasmic release for preloaded L-[3H ]glutamate and [14C ]GABA. However, human tissue studies did not give clear-cut results. Experiments were carried out to optimize the release paradigm as well as to improve the vesicular uptake of labeled transmitters. A 'pulse- chase' protocol, with an unlabelled D-aspartate chase, was performed in human tissue samples in order to enhance the L-[3H ] glutamate release signal derived from exocytosis by removing the cytoplasmic pool of L-[3H ] glutamate first. However, the results showed that total release was not enhanced effectively in comparison with the non-pulse-chase protocol. In brief, the pulse-chase protocol did not build up the vesicular pool of L-[3H ]glutamate, though the cytoplasmic L- [3H ] glutamate pool was effectively depressed by D-aspartate. Further studies applied 4- aminopyridine (4-AP) to trigger release, to circumvent the problem of the reversal of plasma membrane transporters caused by raised K+ ion concentrations. The results showed that the application of 4-AP elicited the release of amino acid transmitters from rat synaptosomes, but failed to produce successful release signals in the human tissue experiments. Our findings suggest that the vesicular compartment may be impaired by freezing and affected by post-mortem delay (PMD). Rat studies showed that the freezing step had a major effect on Ca 2+-dependent release, as less L- [3 H ]glutamate and [14C ]GABA were released from the frozen rat tissue preparations. Moreover, there was an indication of a decline in L-[3H ]glutamate release with increasing PMD. Copyright (2001) Australian Neuroscience Society

  3. Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Thastrup, Ole;

    1987-01-01

    Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S...

  4. pH-Triggered release from surface-modified poly(lactic-co-glycolic acid nanoparticles

    Directory of Open Access Journals (Sweden)

    Manuel Häuser

    2015-12-01

    Full Text Available Nanoparticles (NP of poly(lactic-co-glycolic acid (PLGA represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid (PAA as a pH-sensitive component and poly(diallyldimethylammonium chloride (PDADMAC as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative 1H NMR, yielding a pH-dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by 1H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH-sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative.

  5. Some remarks on hydrogen release from nitric acid solutions

    International Nuclear Information System (INIS)

    After a survey of the literature on generalisable statements on β, γ-radiolysis of water and salty solutions, an attempt is made to summarize and evaluate existing measurements in connection with the formation of H2 in nitrous fission product solutions (or corresponding simulates). It is seen that laboratory experiments with such fission products show rather uniform and plausible G(H2)-values in the region -3. It is also seen, however, that G(H2)-values and steady H2-release rates are not suitable to describe technical systems (HAW stores). Either H2 is carried away by purge air or it is, in a non-operating system, consumed again in situ, obviously by back reactions. (orig.)

  6. [Synthesis, characterization and in vitro release of poly (succinimide-co-4-aminobutanoic acid) by acid-catalyzed polycondensation of L-aspartic acid and 4-aminobutanoic acid].

    Science.gov (United States)

    Liao, Zhiyin; Tang, Guping

    2003-09-01

    For the purpose of increasing the hydrophilicity of poly aspartic acid, a series of polymer of L-aspartic acid and 4-aminobutanoic acid with different ratios (mol/mol) were prepared. The copolymers were characterized by 13CNMR, DSC and x-ray. The confirmed the structures of the polymers. In-vitro tests of release at phosphate buffer saline, enzyme solution of trypsin and papain (37.0 degrees C, pH = 7.4) were carried out. The result indicated that the polymers could be degraded in some degree, and that 4-aminobutanoic acid segments accelerated the degradation rate of the polymers. Skin irritation test and systemic acute toxicity test were carried out, which showed that the polymer was a nontoxic biomedical material. PMID:14564996

  7. Depolarization-induced release of amino acids from the vestibular nuclear complex.

    Science.gov (United States)

    Godfrey, Donald A; Sun, Yizhe; Frisch, Christopher; Godfrey, Matthew A; Rubin, Allan M

    2012-04-01

    There is evidence from immunohistochemistry, quantitative microchemistry, and pharmacology for several amino acids as neurotransmitters in the vestibular nuclear complex (VNC), including glutamate, γ-aminobutyrate (GABA), and glycine. However, evidence from measurements of release has been limited. The purpose of this study was to measure depolarization-stimulated calcium-dependent release of amino acids from the VNC in brain slices. Coronal slices containing predominantly the VNC were prepared from rats and perfused with artificial cerebrospinal fluid (ACSF) in an interface chamber. Fluid was collected from the chamber just downstream from the VNC using a microsiphon. Depolarization was induced by 50 mM potassium in either control calcium and magnesium concentrations or reduced calcium and elevated magnesium. Amino acid concentrations in effluent fluid were measured by high performance liquid chromatography. Glutamate release increased fivefold during depolarization in control calcium concentration and twofold in low calcium/high magnesium. These same ratios were 6 and 1.5 for GABA, 2 and 1.3 for glycine, and 2 and 1.5 for aspartate. Differences between release in control and low calcium/high magnesium ACSF were statistically significant for glutamate, GABA, and glycine. Glutamine release decreased during and after depolarization, and taurine release slowly increased. No evidence for calcium-dependent release was found for serine, glutamine, alanine, threonine, arginine, taurine, or tyrosine. Our results support glutamate and GABA as major neurotransmitters in the VNC. They also support glycine as a neurotransmitter and some function for taurine. PMID:22147284

  8. Sheep erythrocyte membrane binding and transfer of long-chain fatty acids

    DEFF Research Database (Denmark)

    Bojesen, Inge Norby; Bojesen, Eigil

    1999-01-01

    Palmitic acid, oleic acid, linoleic acid, arachidonic acid, sheep erythrocyte ghosts, transporting elements, transport kinetics, fatty acid transport, transport rate constants......Palmitic acid, oleic acid, linoleic acid, arachidonic acid, sheep erythrocyte ghosts, transporting elements, transport kinetics, fatty acid transport, transport rate constants...

  9. In vitro release and antibacterial activity of poly(oleic/linoleic acid dimer:sebacic acid)-gentamicin

    Institute of Scientific and Technical Information of China (English)

    YANGXiu-Fen; ZHOUZhi-Bin; 等

    2003-01-01

    AIM:To investigate whether poly(oleic/linoleic acid dimer:sebacic acid)-getamicin[Poly(OAD/LOAD:SA)-gentamicin]delivery system was useful to treat chronic osteomyelitis.METHODS:Drug delivery system consisted of gentamicin sufate dispersed in a copolymer containing oleic/linoleic acid dimer(OAD/LOAD)and sebacic acid(SA)in a 1:1 weight ration.The gentamicin releast from[Poly(OAD/LOAD:SA)-gentamicin]was tested in water 0.9% saline,and phosphate buffer 0.1mol/L,RESULTS:The gentamicin concentration peak was found on d2,then slowly decreased.considerable amout of gentamicin was still released on d 50.From d 2 o d 50,the gentamicin concentration in the releasing fluids was from 59 to 42128-fold and 1.8 to 1314-fold of the MIC for Staphylococcus aureus and Escherichia coli,respectively.Staphylococcus aureus and Escherichia coli were strongly inhibited by the releasing fluids for 50d.The gentamicin release and anti-bacterial activity in the three media were similar.only in 0.1mol/L phosphate buffer,from d 2 to 14 it was lower.CONCLUSION:Poly(OAD/LOAD:SA)-gentamicin was useful to treat chronic osteomyelitis.

  10. Swelling and Drug Release Characteristics of Poly (methacrylic acid-co-poloxamer) hydrogels

    Institute of Scientific and Technical Information of China (English)

    XUHui; LINYan-nan; DINGPing-tian; TIANMei-juan; ZHENGJun-min

    2003-01-01

    Poly (methacrylie acid co-poloxamer) hydrogel networks were synthesized by free-radical solution polymerization, and the dynamic swelling and in vitro release properties of model drugs, dextromethorphan hydrobromide (DMP) and vitamin B12 (VB12) were studied. These gels exhibited pH-dependant swelling and sustained drug release properties, and the water uptake rate and drug release rate in neutral or basic media were higher than that in acidic media. The results showed that the water uptake followed non-Fickian or zero order process in neutral or basic media, and the release of model drugs from hydrogels of appropriate composition was of zero order kinetics over a period of several hours.

  11. pH-Triggered release from surface-modified poly(lactic-co-glycolic acid) nanoparticles

    OpenAIRE

    Manuel Häuser; Klaus Langer; Monika Schönhoff

    2015-01-01

    Nanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium...

  12. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors

    DEFF Research Database (Denmark)

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.;

    2015-01-01

    -coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L......Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium......-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing...

  13. Arachidonate 12-lipoxygenases with reference to their selective inhibitors

    International Nuclear Information System (INIS)

    Lipoxygenase is a dioxygenase recognizing a 1-cis,4-cis-pentadiene of polyunsaturated fatty acids. The enzyme oxygenates various carbon atoms of arachidonic acid as a substrate and produces 5-, 8-, 12- or 15-hydroperoxy eicosatetraenoic acid with a conjugated diene chromophore. The enzyme is referred to as 5-, 8-, 12- or 15-lipoxygenase, respectively. Earlier we found two isoforms of 12-lipoxygenase, leukocyte- and platelet-type enzymes, which were distinguished by substrate specificity, catalytic activity, primary structure, gene intron size, and antigenicity. Recently, the epidermis-type enzyme was found as the third isoform. Attempts have been made to find isozyme-specific inhibitors of 12-lipoxygenase, and earlier we found hinokitol, a tropolone, as a potent inhibitor selective for the platelet-type 12-lipoxygenase. More recently, we tested various catechins of tea leaves and found that (-)-geotechnical gallate was a potent and selective inhibitor of human platelet 12-lipoxygenase with an IC5 of 0.14 μM. The compound was much less active with 12-lipoxygenase of leukocyte-type, 15-, 8-, and 5-lipoxygenases, and cyclo oxygenases-1 and -2

  14. Bile acid induced colonic irritation stimulates intracolonic nitric oxide release in humans.

    OpenAIRE

    F. Casellas; Mourelle, M; Papo, M; Guarner, F; Antolin, M; Armengol, J R; J. R. Malagelada

    1996-01-01

    AIM--To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA). PATIENTS--Seven patients with irritable bowel syndrome. METHODS--The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can...

  15. The effect of humic acids on the element release from high level waste glass

    International Nuclear Information System (INIS)

    Eu and Am doped glasses were interacted with synthetic interstitial clay water (SiC) and corresponding reference leachant, humic acids free interstitial solution (IS) to investigate the influence of humic acids on the leaching behavior of the waste glass. Static leach tests were carried out at 40 C and 90 C. The release of the lanthanide Eu and the actinide Am from the glass was obviously enhanced by the presence of humic acids. The leaching of transition elements, Fe and Ti strongly depends on the humic acids concentration. The leaching of glass matrix components, Al and B was also influenced by the concentrations of humic acids. However, humic acids have little effect on the leaching of glass matrix element Si

  16. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

    International Nuclear Information System (INIS)

    Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of 125I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid

  17. Bile acids trigger GLP-1 release predominantly by accessing basolaterally-located G-protein coupled bile acid receptors

    DEFF Research Database (Denmark)

    Brighton, Cheryl A; Rievaj, Juraj; Kuhre, Rune Ehrenreich; Glass, Leslie L; Schoonjans,, Kristina; Holst, Jens Juul; Gribbe, Fiona M; Reimann, Frank

    2015-01-01

    coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release, and whether bile acids target their receptors on GLP-1 secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L...... significant effect in non-polarised primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminalTDCA.Intestinal primary culturesandUssingchamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA...

  18. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    Directory of Open Access Journals (Sweden)

    Wen-Hao Wei

    2015-03-01

    Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

  19. Omega-6 Fatty Acids

    Science.gov (United States)

    ... Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other ... ACIDS are as follows:Improving mental development or growth in infants. Adding arachidonic acid (an omega-6 ...

  20. Acacia-gelatin microencapsulated liposomes: preparation, stability, and release of acetylsalicylic acid.

    Science.gov (United States)

    Dong, C; Rogers, J A

    1993-01-01

    Liposomes of dipalmitoylphosphatidylcholine (DPPC) containing acetylsalicylic acid (ASA) have been microencapsulated by acacia-gelatin using the complex coacervation technique as a potential oral drug delivery system. The encapsulation efficiency of ASA was unaltered by the microencapsulation process. The stability of the microencapsulated liposomes in sodium cholate solutions at pH 5.6 was much greater than the corresponding liposomes. The optimum composition and conditions for stability and ASA release were 3.0% acacia-gelatin and a 1- to 2-hr formaldehyde hardening time. Approximately 25% ASA was released in the first 6 hr from microencapsulated liposomes at 23 degrees C and the kinetics followed matrix-controlled release (Q varies; is directly proportional to t1/2). At 37 degrees C, this increased to 75% released in 30 min followed by a slow constant release, likely due to lowering of the phase transition temperature of DPPC by the acacia-gelatin to near 37 degrees C. At both temperatures, the release from control liposomes was even more rapid. Hardening times of 4 hr and an acacia-gelatin concentration of 5% resulted in a lower stability of liposomes and a faster release of ASA. It is concluded that under appropriate conditions the microencapsulation of liposomes by acacia-gelatin may increase their potential as an oral drug delivery system. PMID:8430052

  1. Controlled release of insulin through hydrogels of (acrylic acid)/trimethylolpropane triacrylate

    Science.gov (United States)

    Raymundi, Vanessa C.; Aguiar, Leandro G.; Souza, Esmar F.; Sato, Ana C.; Giudici, Reinaldo

    2015-12-01

    Hydrogels of poly(acrylic acid) crosslinked with trimethylolpropane triacrylate (TMPTA) were produced through solution polymerization. After these hydrogels were loaded with insulin solution, they evidenced swelling. Experiments of controlled release of insulin through the hydrogels were performed in acidic and basic media in order to evaluate the rates of release of this protein provided by the referred copolymer. Additionally, a mathematical description of the system based on differential mass balance was made and simulated in MATLAB. The model consists of a system of differential equations which was solved numerically. As expected, the values of swelling index at the equilibrium and the rates of insulin release were inversely proportional to the degree of crosslinking. The mathematical model provided reliable predictions of release profiles with fitted values of diffusivity of insulin through the hydrogels in the range of 6.0 × 10-7-1.3 × 10-6 cm2/s. The fitted and experimental values of partition coefficients of insulin between the hydrogel and the medium were lower for basic media, pointing out good affinity of insulin for these media in comparison to the acidic solutions.

  2. Microbial release of 2,4-dichlorophenyl bound to humic acid or incorporated during humification

    International Nuclear Information System (INIS)

    The microbial release of 14C-labeled 2,4-dichlorophenol (DCP) bound to synthetic and natural humic materials or polymerized by enzymes was investigated to evaluate the possibility of future adverse effects if binding or polymerization is used for decontamination purposes. After 12 wk of incubation with microorganisms obtained from a forest soil, the amounts of substances released into the media were very small (maximum 2.2% of the initially bound 14C) without regard to the kind of the polymer into which 14C-DCP was incorporated. Most of the radioactivity (46.2 to 80.8%) remained bound to the precipitated humic materials or in the DCP-polymer (90.1 to 97.0%). Certain amounts of the released substances evolved in the form of 14CO2 (1.0 to 9.4% from humic materials and 0 to 0.5% from a DCP-polymer). The rate of mineralization differed depending on the type of DCP binding - surface-bound or incorporated during synthesis of humic acid - and on the kind of polymer to which 14C-DCP was attached. The release into the media and 14CO2 evolution for synthetic and natural humic acids was essentially the same. When only DCP was present in the growth medium, the formation of 14CO2 was less than from a DCP-humic acid complex; this may indicate that 14CO2 from a DCP-humic acid complex originated mostly from DCP derivatives. The data obtained for DCP did not provide any evidence for a delayed pollution problem associated with polymerization or binding of xenobiotics to humic acids

  3. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors.

    Science.gov (United States)

    Brighton, Cheryl A; Rievaj, Juraj; Kuhre, Rune E; Glass, Leslie L; Schoonjans, Kristina; Holst, Jens J; Gribble, Fiona M; Reimann, Frank

    2015-11-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

  4. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein–Coupled Bile Acid Receptors

    Science.gov (United States)

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.; Glass, Leslie L.; Schoonjans, Kristina; Holst, Jens J.

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

  5. Intracellular release of rapamycin from poly (lactic acid) nanospheres modifies autophagy.

    Science.gov (United States)

    Nagata, Junpei; Matsui, Makoto; Tabata, Yasuhiko

    2016-09-01

    The objective of this study is to investigate the autophagy activity of cells by the intracellular release of rapamycin (Rapa) of an autophagy inducer. Rapa was incorporated into nanospheres of poly (lactic-co-glycolic acid) (PLGA) for the controlled release of Rapa. Rapa was released from the PLGA nanospheres incorporating rapamycin (Rapa-PLGA-NS) with time while the Rapa-PLGA-NS were hydrolytically degraded. When human hepatocellular carcinoma (HepG2) cells were incubated with the Rapa-PLGA-NS, the Rapa-PLGA-NS were internalized, and the intracellular concentration was maintained over four days, indicating the intracellular Rapa release. The microtubule-associated protein 1 light chain (LC3) of an autophagy marker was significantly high for the Rapa-PLGA-NS group compared with the free Rapa group even after four days incubation. In addition, intracellular harmful ubiquitinated proteins were degraded by the intracellular release of Rapa even after four days incubation in contrast to free Rapa. It is concluded that the intracellular Rapa release is effective in modulating the autophagy activity over a longer time period. PMID:27320771

  6. The use of bone cement for the localized, controlled release of the antibiotics vancomycin, linezolid, or fusidic acid: effect of additives on drug release rates and mechanical strength.

    Science.gov (United States)

    Jackson, John; Leung, Fay; Duncan, Clive; Mugabe, Clement; Burt, Helen

    2011-04-01

    Bone cement containing antibiotics is commonly used to treat orthopedic related infections. However, effective treatment (especially of resistant bacteria, methacillin-resistant Staphylococcus aureus (MRSA)) is compromised by very low levels of drug release so that typically less than 10% of loaded drug is released over a 6-week period. The objective of this study was to investigate the effect of incorporation of water soluble excipients (polyethylene glycol, sodium chloride, or dextran) into antibiotic-loaded cement on mechanical strength and drug release properties. Poly(methyl methylacrylate) cement implants containing various amounts of drug (vancomycin, linezolid or fusidic acid (all MRSA active)) and excipients were cast in the form of beads or films and characterized using differential scanning calorimetry. Mechanical strength as assessed by Young's modulus was determined by thermo-mechanical analysis. Drug release was measured by incubation in phosphate buffered saline with analysis by HPLC methods. The inclusion of sodium chloride up to 20% w/w caused only minor reductions in Young's modulus. Vancomycin and linezolid released very slowly from unmodified bone cement beads (less than 3% released by 4 weeks) whereas fusidic acid released more quickly (approximately 8% released by 4 weeks). The inclusion of sodium chloride or dextran in bone cement resulted in major increases in the release rate of vancomycin, linezolid and fusidic acid. These studies support the inclusion of sodium chloride and dextran in bone cement to increase the release rate of vancomycin, linezolid, or fusidic acid without compromising the mechanical strength of the composite material. PMID:25788111

  7. Naringin administration inhibits platelet aggregation and release by reducing blood cholesterol levels and the cytosolic free calcium concentration in hyperlipidemic rabbits

    OpenAIRE

    Xiao, Yang; LI, LAI-LAI; Guo, Jing-Jing; XU, WEN-PING; Wang, Yan-Yan; Wang, Yi

    2014-01-01

    This study investigated the effects of naringin on platelet aggregation and release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of naringin was also investigated. The rabbits were orally administered 60, 30 or 15 mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol diet for four weeks. Following the two weeks of drug administration, the degree of platelet aggregation induced by arachidonic acid, adenosine diphosphate and collagen was signifi...

  8. Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release.

    Science.gov (United States)

    Ichikawa, Junji; Chung, Young-Chul; Dai, Jin; Meltzer, Herbert Y

    2005-08-01

    Antipsychotic drugs (APD)s and anticonvulsant mood-stabilizers are now frequently used in combination with one another in treating both schizophrenia and bipolar disorder. We have recently reported that the atypical APDs, e.g. clozapine and risperidone, as well as the anticonvulsant mood-stabilizers, valproic acid (VPA), zonisamide, and carbamazepine, but not the typical APD haloperidol, increase dopamine (DA) release in rat medial prefrontal cortex (mPFC). The increased DA release was partially (atypical APDs) or completely (mood-stabilizers) blocked by the serotonin (5-HT)1A receptor antagonist WAY100635. Diminished prefrontal cortical DA activity may contribute to cognitive impairment in virtually all the patients with schizophrenia and, perhaps, bipolar disorder. Thus, the enhanced release of cortical DA by these agents may be beneficial in this regard. It is, therefore, of considerable interest to determine whether combined administration of these agents augments prefrontal cortical DA release, and if so, whether the increase is dependent upon 5-HT1A receptor activation. VPA (50 mg/kg), which was insufficient by itself to increase prefrontal cortical DA release, potentiated the ability of clozapine (20 mg/kg) and risperidone (1 mg/kg) to increase DA release in the mPFC, but not in the nucleus accumbens (NAC). VPA (50 mg/kg) also potentiated haloperidol (0.5 mg/kg)-induced DA release in the mPFC; this increase was completely abolished by WAY100635 (0.2 mg/kg). These results suggest that, in combination with VPA, both typical and atypical APDs produce greater increases in prefrontal cortical DA release than either type of drug alone via a mechanism dependent upon 5-HT(1A) receptor activation. Furthermore, they provide a strong rationale for testing for possible clinical synergism of an APD and anticonvulsant mood-stabilizer in improving the cognitive deficits present in patients with schizophrenia and bipolar disorder. PMID:16061211

  9. Bile acid effects are mediated by ATP release and purinergic signalling in exocrine pancreatic cells

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena; Haanes, Kristian Agmund; Christensen, Nynne;

    2015-01-01

    BACKGROUND: In many cells, bile acids (BAs) have a multitude of effects, some of which may be mediated by specific receptors such the TGR5 or FXR receptors. In pancreas systemic BAs, as well as intra-ductal BAs from bile reflux, can affect pancreatic secretion. Extracellular ATP and purinergic......) and duct cells (Capan-1). Taurine and glycine conjugated forms of CDCA had smaller effects on ATP release in Capan-1 cells. In duct monolayers, CDCA stimulated ATP release mainly from the luminal membrane; the releasing mechanisms involved both vesicular and non-vesicular secretion pathways. Duct...... cells were not depleted of intracellular ATP with CDCA, but acinar cells lost some ATP, as detected by several methods including ATP sensor AT1.03(YEMK). In duct cells, CDCA caused reversible increase in the intracellular Ca(2+) concentration [Ca(2 +)]i, which could be significantly inhibited by...

  10. Nigella sativa L. Seed Extract Modulates the Neurotransmitter Amino Acids Release in Cultured Neurons In Vitro

    OpenAIRE

    Tarek El-Naggar; María Pilar Gómez-Serranillos; Olga María Palomino; Carmen Arce; María Emilia Carretero

    2010-01-01

    Nigella sativa L. (NS) has been used for medicinal purposes since ancient times. This study aimed to investigate the cytotoxicity of NS dry methanolic extract on cultured cortical neurons and its influence on neurotransmitter release, as well as the presence of excitatory (glutamate and aspartate) and inhibitory amino acids (gamma-aminobutyric acid—GABA—and glycine) in NS extract. Cultured rat cortical neurons were exposed to different times and concentrations of NS dry methanolic extract and...

  11. Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

    Energy Technology Data Exchange (ETDEWEB)

    Li Fengxia [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China); Li Xiaoli, E-mail: lixiaoli0903@163.com [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China); Li Bin, E-mail: libinzh62@163.com [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China)

    2011-11-15

    In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 {mu}m. Magnetic Fe{sub 3}O{sub 4} was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h. - Highlights: > We prepare magnetic polylactic acid microspheres loading curcumin. > The classical oil-in-water emulsion solvent-evaporation method is used. > The magnetic microspheres are regularly spherical with a diameter of 0.55-0.75 {mu}m. > They show a certain sustained release effect on in vitro drug releasing.

  12. Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

    International Nuclear Information System (INIS)

    In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe3O4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h. - Highlights: → We prepare magnetic polylactic acid microspheres loading curcumin. → The classical oil-in-water emulsion solvent-evaporation method is used. → The magnetic microspheres are regularly spherical with a diameter of 0.55-0.75 μm. → They show a certain sustained release effect on in vitro drug releasing.

  13. Inherently antioxidant and antimicrobial tannic acid release from poly(tannic acid) nanoparticles with controllable degradability.

    Science.gov (United States)

    Sahiner, Nurettin; Sagbas, Selin; Aktas, Nahit; Silan, Coskun

    2016-06-01

    From a natural polyphenol, Tannic acid (TA), poly(TA) nanoparticles were readily prepared using a single step approach with three different biocompatible crosslinkers; trimethylolpropane triglycidyl ether (TMPGDE), poly(ethylene glycol) diglycidyl ether (PEGGE), and trisodium trimetaphosphate (STMP). P(TA) particles were obtained with controllable diameters between 400 to 800nm with -25mV surface charge. The effect of synthesis conditions, such as the emulsion medium, pH values of TA solution, and the type of crosslinker, on the shape, size, dispersity, yield, and degradability of poly(Tannic Acid) (p(TA)) nanoparticles was systematically investigated. The hydrolytic degradation amount in physiological pH conditions of 5.4, 7.4, and 9.0 at 37.5°C were found to be in the order TMPGDEantimicrobial effects against common bacterial strains. More interestingly, with a higher concentration of p(TA) particles, higher blood clotting indices were obtained. PMID:26970821

  14. Release of Ciprofloxacin-HCl and Dexamethasone Phosphate by Hyaluronic Acid Containing Silicone Polymers

    Directory of Open Access Journals (Sweden)

    Lyndon Jones

    2012-04-01

    Full Text Available The purpose of this study was to determine the effect of the covalent incorporation of hyaluronic acid (HA into conventional hydrogel and hydrogels containing silicone as models for contact lens materials on the uptake and release of the fluoroquinolone antibiotic ciprofloxacin and the anti-inflammatory steroid dexamethasone phosphate. A 3 mg/mL ciprofloxacin solution (0.3% w/v and a 1 mg/mL dexamethasone phosphate solution (0.1% was prepared in borate buffered saline. Three hydrogel material samples (pHEMA; pHEMA TRIS; DMAA TRIS were prepared with and without the covalent incorporation of HA of molecular weight (MW 35 or 132 kDa. Hydrogel discs were punched from a sheet of material with a uniform diameter of 5 mm. Uptake kinetics were evaluated at room temperature by soaking the discs for 24 h. Release kinetics were evaluated by placing the drug-loaded discs in saline at 34 °C in a shaking water bath. At various time points over 6–7 days, aliquots of the release medium were assayed for drug amounts. The majority of the materials tested released sufficient drug to be clinically relevant in an ophthalmic application, reaching desired concentrations for antibiotic or anti-inflammatory activity in solution. Overall, the silicone-based hydrogels (pHEMA TRIS and DMAA TRIS, released lower amounts of drug than the conventional pHEMA material (p < 0.001. Materials with HA MW132 released more ciprofloxacin compared to materials with HA MW35 and lenses without HA (p < 0.02. Some HA-based materials were still releasing the drug after 6 days.

  15. Polyunsaturated fatty acids and inflammation

    OpenAIRE

    Calder Philip C

    2004-01-01

    The n-6 polyunsaturated fatty acid arachidonic acid gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites) and through these regulates the activities of inflammatory cells, the production of cytokines and the various balances within the immune system. Fish oil and oily fish are good sources of long chain n-3 polyunsaturated fatty acids. Consumption of these fatty acids decreases the amount of arachidonic acid in cell membranes and ...

  16. Interleukin-2 stimulates osteoclastic activity: Increased acid production and radioactive calcium release

    International Nuclear Information System (INIS)

    Recombinant human interleukin-2 (IL-2) was studied to determine effects on acid production by individual osteoclasts in situ on mouse calvarial bones. This analysis was performed using a microspectrofluorimetric technique to quantify acid production in individual cells. Radioactive calcium release was determined using calvarial bones in a standard tissue culture system. This allowed us to correlate changes in acid production with a measure of bone resorption. IL-2 stimulated acid production and bone resorbing activity. Both effects were inhibited by calcitonin. No stimulation of bone resorption occurred when IL-2-containing test media was incubated with a specific anti-IL-2 antibody and ultrafiltered. Our data demonstrated a correlation between acid production and bone resorbing activity in mouse calvaria exposed to parathyroid hormone (PTH). The data obtained from cultured mouse calvaria exposed to IL-2 demonstrated similar stimulatory effects to those seen during PTH exposure. These data suggest that calvaria exposed to IL-2 in vitro have increased osteoclastic acid production corresponding with increased bone resorption. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Properties and mechanisms of drug release from matrix tablets containing poly(ethylene oxide) and poly(acrylic acid) as release retardants.

    Science.gov (United States)

    Zhang, Feng; Meng, Fan; Lubach, Joseph; Koleng, Joseph; Watson, N A

    2016-08-01

    The interactions between poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) in aqueous medium at pH 6.8 were investigated in the current study. We have also studied the effect of interpolymer interactions and various formulation variables, including the molecular weight of PEO, the ratio between PEO and PAA, the crystallinity of PEO, and the presence of an acidifying agent, on the release of theophylline from matrix tablets containing both PEO and PAA as release retardants. At pH 6.8, the synergy in solution viscosity between PEO and PAA as the result of ion-dipole interaction was observed in this study. The release of theophylline from the matrix tablets containing physical mixtures of PEO and PAA was found to be a function of dissolution medium pH because of the pH-dependent interactions between these two polymers. Because of the formation of water insoluble interpolymer complex between PEO and PAA in aqueous medium at pH below 4.0, the release of theophylline was independent of PEO molecular weight and was controlled by Fickian diffusion mechanism in 0.01N hydrochloric acid solution. In comparison, the drug release was a function of PEO molecular weight and followed the anomalous transport mechanism in phosphate buffer pH 6.8. The presence of PAA exerted opposite effects on the release of theophylline in phosphate buffer pH 6.8. In one aspect, theophylline release was accelerated because the erosion of PAA was much faster than that of PEO at pH6.8. On the opposite aspect, theophylline release was slowed down because of the formation of insoluble complex inside the gel layer as the result of the acidic microenvironment induced by PAA, and the increase in the viscosity of the gel layer as the result of the synergy between PEO and PAA. These two opposite effects offset each other. As a result, the release of theophylline remained statistically the same even when 75% PEO in the formulation was replaced with PAA. In phosphate buffer pH 6.8, the release of

  19. The cysteine releasing pattern of some antioxidant thiazolidine-4-carboxylic acids.

    Science.gov (United States)

    Önen Bayram, F Esra; Sipahi, Hande; Acar, Ebru Türköz; Kahveci Ulugöl, Reyhan; Buran, Kerem; Akgün, Hülya

    2016-05-23

    Oxidative stress that corresponds to a significant increase in free radical concentration in cells can cause considerable damage to crucial biological macromolecules if not prevented by cellular defense mechanisms. The low-molecular-weight thiol glutathione (GSH) constitutes one of the main intracellular antioxidants. It is synthesized via cysteine, an amino acid found only in limited amounts in cells because of its neurotoxicity. Thus, to ensure an efficient GSH synthesis in case of an oxidative stress, cysteine should be provided extracellularly. Yet, given its nucleophilic properties and its rapid conversion into cystine, its corresponding disulfide, cysteine presents some toxicity and therefore is usually supplemented in a prodrug approach. Here, some thiazolidine-4-carboxylic acids were synthesized and evaluated for their antioxidant properties via the DDPH and CUPRAC assays. Then, the cysteine releasing capacity of the obtained compounds was investigated in aqueous and organic medium in order to correlate the relevant antioxidant properties of the molecules with their cysteine releasing pattern. As a result, the structures' antioxidative properties were not only attributed to cysteine release but also to the thiazolidine cycle itself. PMID:27017266

  20. Controlled release of anti-diabetic drug Gliclazide from poly(caprolactone)/poly(acrylic acid) hydrogels.

    Science.gov (United States)

    Bajpai, S K; Chand, Navin; Soni, Shweta

    2015-01-01

    Drug Gliclazide (Glz) has limited solubility and low bioavailability. In order to obtain a controlled release of this drug and to improve its bioavailability, the drug has been loaded into poly(caprolactone) (PCL)/poly(acrylic acid) (PAAc) hydrogels, prepared by free radical polymerization of acrylic acid in the presence of poly(caprolactone) in acetone medium using azo-isobutyronitrile as initiator and N,N' methylene bisacrylamide as cross-linking agent. The swelling behaviour of these hydrogels has been investigated in the physiological gastric and intestinal fluids to obtain an optimum composition suitable for delivery of a biologically active compound. The gels were loaded with anti-diabetic drug Glz and a detailed investigation of release of drug has been carried out. Various kinetic models have been applied on the release data. Finally, the Albino wistar rats were treated for Streptozotocin plus nicotinamide - induced diabetes using a Glz-loaded PCL/PAAc hydrogel. The results indicated a fair reduction in the glucose level of rats. PMID:26135033

  1. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    International Nuclear Information System (INIS)

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite

  2. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Zargarian, S. Sh.; Haddadi-Asl, V., E-mail: haddadi@aut.ac.ir; Hematpour, H. [Amirkabir University of Technology, Department of Polymer Engineering and Color Technology (Iran, Islamic Republic of)

    2015-05-15

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite.

  3. Effect of lactobionic acid on the acidification, rheological properties and aroma release of dairy gels.

    Science.gov (United States)

    Ribeiro, Jéssica C Bigaski; Granato, Daniel; Masson, Maria Lucia; Andriot, Isabelle; Mosca, Ana Carolina; Salles, Christian; Guichard, Elisabeth

    2016-09-15

    The food industry is investigating new technological applications of lactobionic acid (LBA). In the current work, the effect of lactobionic acid on the acidification of dairy gels (pH 5.5 and 6.2), rheological properties using a double compression test, sodium mobility using (23)Na NMR technique and aroma release using headspace GC-FID were studied. Our results showed that it is possible to use LBA as an alternative to glucono-δ-lactone (GDL) for the production of dairy gels with a controlled pH value. Small differences in the rheological properties and in the amount of aroma volatile organic compounds that were released in the vapour phase, but no significant difference in the sodium ion mobility were obtained. The gels produced with LBA were less firm and released less volatile aroma compounds than the gels produced with GDL. The gels at pH 6.2 were firmer than those at pH 5.5 and had a more organised structure around the sodium ions. PMID:27080885

  4. Enhanced Nitrogen Availability in Karst Ecosystems by Oxalic Acid Release in the Rhizosphere.

    Science.gov (United States)

    Pan, Fujing; Liang, Yueming; Zhang, Wei; Zhao, Jie; Wang, Kelin

    2016-01-01

    In karst ecosystems, a high level of CaCO3 enhances the stabilization of soil organic matter (SOM) and causes nitrogen (N) and/or phosphorus (P) limitation in plants. Oxalic acid has been suggested to be involved in the nutrient-acquisition strategy of plants because its addition can temporarily relieve nutrient limitation. Therefore, understanding how oxalic acid drives N availability may help support successful vegetation restoration in the karst ecosystems of southwest China. We tested a model suggested by Clarholm et al. (2015) where oxalate reacts with Ca bridges in SOM, thus exposing previously protected areas to enzymatic attacks in a way that releases N for local uptake. We studied the effects of oxalic acid, microbial biomass carbon (MBC), and β-1,4-N-acetylglucosaminidase (NAG) on potential N mineralization rates in rhizosphere soils of four plant species (two shrubs and two trees) in karst areas. The results showed that rhizosphere soils of shrubs grown on formerly deforested land had significantly lower oxalic acid concentrations and NAG activity than that of trees in a 200-year-old forest. The levels of MBC in rhizosphere soils of shrubs were significantly lower than those of trees in the growing season, but the measure of shrubs and trees were similar in the non-growing season; the potential N mineralization rates showed a reverse pattern. Positive relationships were found among oxalic acid, MBC, NAG activity, and potential N mineralization rates for both shrubs and trees. This indicated that oxalic acid, microbes, and NAG may enhance N availability for acquisition by plants. Path analysis showed that oxalic acid enhanced potential N mineralization rates indirectly through inducing microbes and NAG activities. We found that the exudation of oxalic acid clearly provides an important mechanism that allows plants to enhance nutrient acquisition in karst ecosystems. PMID:27252713

  5. Enhanced Nitrogen Availability in Karst Ecosystems by Oxalic Acid Release in the Rhizosphere

    Science.gov (United States)

    Pan, Fujing; Liang, Yueming; Zhang, Wei; Zhao, Jie; Wang, Kelin

    2016-01-01

    In karst ecosystems, a high level of CaCO3 enhances the stabilization of soil organic matter (SOM) and causes nitrogen (N) and/or phosphorus (P) limitation in plants. Oxalic acid has been suggested to be involved in the nutrient-acquisition strategy of plants because its addition can temporarily relieve nutrient limitation. Therefore, understanding how oxalic acid drives N availability may help support successful vegetation restoration in the karst ecosystems of southwest China. We tested a model suggested by Clarholm et al. (2015) where oxalate reacts with Ca bridges in SOM, thus exposing previously protected areas to enzymatic attacks in a way that releases N for local uptake. We studied the effects of oxalic acid, microbial biomass carbon (MBC), and β-1,4-N-acetylglucosaminidase (NAG) on potential N mineralization rates in rhizosphere soils of four plant species (two shrubs and two trees) in karst areas. The results showed that rhizosphere soils of shrubs grown on formerly deforested land had significantly lower oxalic acid concentrations and NAG activity than that of trees in a 200-year-old forest. The levels of MBC in rhizosphere soils of shrubs were significantly lower than those of trees in the growing season, but the measure of shrubs and trees were similar in the non-growing season; the potential N mineralization rates showed a reverse pattern. Positive relationships were found among oxalic acid, MBC, NAG activity, and potential N mineralization rates for both shrubs and trees. This indicated that oxalic acid, microbes, and NAG may enhance N availability for acquisition by plants. Path analysis showed that oxalic acid enhanced potential N mineralization rates indirectly through inducing microbes and NAG activities. We found that the exudation of oxalic acid clearly provides an important mechanism that allows plants to enhance nutrient acquisition in karst ecosystems. PMID:27252713

  6. Facile method to prepare silk fibroin/hyaluronic acid films for vascular endothelial growth factor release.

    Science.gov (United States)

    Zhou, Juan; Zhang, Bin; Liu, Xunwei; Shi, Lijun; Zhu, Jun; Wei, Daixu; Zhong, Jian; Sun, Gang; He, Dannong

    2016-06-01

    A facile approach was proposed to prepare silk fibroin (SF) and hyaluronic acid (HA) composite films from aqueous solution without crosslinking or any post treatment. Only by controlling the HA content and film formation temperature during the film casting, the HA/SF films with different composition were prepared. The films were then characterized by structural characteristics, thermal stability, morphology, water stability, water absorption, mechanical properties. After immersing in water for 24h, all of the films showed good structural integrity. The degradation rate of the HA/SF films in protease XIV can be controlled by changing the film formation temperature and HA content. Decreasing the temperature and adding HA resulted in the rapid release of VEGF (vascular endothelial growth factor) from the HA/SF films. Overall, the 5% HA/SF films formed at 37°C with more rapid VEGF release exhibited great potential in drug delivery, especially when the rapid vascularization was needed. PMID:27083373

  7. Controlled release of acetylsalicylic acid from polythiophene/carrageenan hydrogel via electrical stimulation.

    Science.gov (United States)

    Pairatwachapun, Sanita; Paradee, Nophawan; Sirivat, Anuvat

    2016-02-10

    Blends between polythiophene (PTh) and a carrageenan hydrogel were fabricated as the matrix for the electric field assisted drug release. The pristine carrageenan and the blend films were prepared by the solution casting using acetylsalicylic acid (ASA) as the anionic model drug and Mg(2+), Ca(2+), and Ba(2+) as the crosslinking agents. The ASA was released by the Fickian diffusion mechanism. The diffusion coefficient decreased with increasing crosslinking ratio or decreasing crosslinking ionic radii. The diffusion coefficients were greater with the applied electrical potentials by an order of magnitude relative to those without electric field. Moreover, the diffusion coefficients with PTh as the drug carrier were higher than those without PTh. Thus, the presence of the conductive polymer in the hydrogel blend coupled with applied electric field is shown here to drastically enhance the drug delivery rate. PMID:26686123

  8. Acid neutralization mechanisms and metal release in mine tailings: a laboratory column experiment

    Science.gov (United States)

    Jurjovec, Jasna; Ptacek, Carol J.; Blowes, David W.

    2002-05-01

    Mining and milling of base metal ore deposits can result in the release of metals to the environment. When sulfide minerals contained in mine tailings are exposed to oxygen and water, they oxidize and dissolve. Two principal antagonistic geochemical processes affect the migration of dissolved metals in tailings impoundments: sulfide oxidation and acid neutralization. This study focuses on acid neutralization reactions occurring in the saturated zone of tailings impoundments. To simulate conditions prevailing in many tailings impoundments, 0.1 mol/L sulfuric acid was passed continuously through columns containing fresh, unoxidized tailings, collected at Kidd Creek metallurgical site. The results of this column experiment represent a detailed temporal observation of pH, Eh, and metal concentrations. The results are consistent with previous field observations, which suggest that a series of mineral dissolution-precipitation reactions control pH and metal mobility. Typically, the series consists of carbonate minerals, Al and Fe(III) hydroxides, and aluminosilicates. In the case of Kidd Creek tailings, the dissolution series consists of ankerite-dolomite, siderite, gibbsite, and aluminosilicates. In the column experiment, three distinct pH plateaus were observed: 5.7, 4.0, and 1.3. The releases of trace elements such as Cd, Co, Cr, Cu, Li, Ni, Pb, V, and Zn were observed to be related to the pH buffering zones. High concentrations of Zn, Ni, and Co were observed at the first pH plateau (pH 5.7), whereas Cd, Cr, Pb, As, V, and Al were released as the pH of the pore water decreased to 4.0 or less.

  9. Influence of fatty acid oxidation rate on glycerol release from cardiac myocytes

    International Nuclear Information System (INIS)

    Quiescent cardiac myocytes are characterized by low rates of fatty acid oxidation due to the reduced energy demand compared with beating hearts. The accumulation of intracellular fatty acid metabolites may, therefore, result in feed-back inhibition of the cardiac lipase responsible for the mobilization of triacylglycerols (lipolysis). The objective of this study was to examine if interventions that increase fatty acid oxidation rates in myocytes have an effect on lipolysis. Addition of 100 μM dinitrophenol (DNP) to calcium-tolerant rat ventricular myocytes caused an increase in the rate of 14C-oleic acid oxidation from 1.11 +/- 0.06 to 2.38 +/- 0.17 nmol 14CO2/106 cells/min (115% stimulation; mean +/- S.D., n = 3). In parallel incubations, DNP increased the rate of lipolysis from 4.4 +/- 1.7 to 13.6 +/- 3.2 nmol glycerol/106 cells/30 min (215% stimulation). The addition of 1 mM barium to a modified Ringer's incubation medium produced an increase in the contractile activity of the myocytes, and increased the rates of oleic acid oxidation from 0.62 +/- 0.16 to 0.88 +/- 0.23 nmol/106 cells/min (42% stimulation; n = 6) and lipolysis from 13.1 +/- 6.5 to 22.2 +/- 6.4 nmol/106 cells/30 min (70% stimulation). These data show that stimulation of fatty acid oxidation in myocardial myocytes is accompanied by increased lipolytic rates, the latter probably due to release of feed-back inhibition of cardiac lipases by accumulated fatty acid metabolites

  10. Influence of fatty acid oxidation rate on glycerol release from cardiac myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, T.S.; Severson, D.L.

    1986-03-05

    Quiescent cardiac myocytes are characterized by low rates of fatty acid oxidation due to the reduced energy demand compared with beating hearts. The accumulation of intracellular fatty acid metabolites may, therefore, result in feed-back inhibition of the cardiac lipase responsible for the mobilization of triacylglycerols (lipolysis). The objective of this study was to examine if interventions that increase fatty acid oxidation rates in myocytes have an effect on lipolysis. Addition of 100 ..mu..M dinitrophenol (DNP) to calcium-tolerant rat ventricular myocytes caused an increase in the rate of /sup 14/C-oleic acid oxidation from 1.11 +/- 0.06 to 2.38 +/- 0.17 nmol /sup 14/CO/sub 2//10/sup 6/ cells/min (115% stimulation; mean +/- S.D., n = 3). In parallel incubations, DNP increased the rate of lipolysis from 4.4 +/- 1.7 to 13.6 +/- 3.2 nmol glycerol/10/sup 6/ cells/30 min (215% stimulation). The addition of 1 mM barium to a modified Ringer's incubation medium produced an increase in the contractile activity of the myocytes, and increased the rates of oleic acid oxidation from 0.62 +/- 0.16 to 0.88 +/- 0.23 nmol/10/sup 6/ cells/min (42% stimulation; n = 6) and lipolysis from 13.1 +/- 6.5 to 22.2 +/- 6.4 nmol/10/sup 6/ cells/30 min (70% stimulation). These data show that stimulation of fatty acid oxidation in myocardial myocytes is accompanied by increased lipolytic rates, the latter probably due to release of feed-back inhibition of cardiac lipases by accumulated fatty acid metabolites.

  11. Release of Ciprofloxacin-HCl and Dexamethasone Phosphate by Hyaluronic Acid Containing Silicone Polymers

    OpenAIRE

    Lyndon Jones; Elizabeth Joyce; Heather Sheardown; Miriam Heynen; Andrea Weeks; Alex Hui; Darrene Nguyen

    2012-01-01

    The purpose of this study was to determine the effect of the covalent incorporation of hyaluronic acid (HA) into conventional hydrogel and hydrogels containing silicone as models for contact lens materials on the uptake and release of the fluoroquinolone antibiotic ciprofloxacin and the anti-inflammatory steroid dexamethasone phosphate. A 3 mg/mL ciprofloxacin solution (0.3% w/v) and a 1 mg/mL dexamethasone phosphate solution (0.1%) was prepared in borate buffered saline. Three hydrogel mater...

  12. Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

    Directory of Open Access Journals (Sweden)

    Tzu-Yu Lin

    Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

  13. Inhibition of bleomycin-induced pulmonary fibrosis by nordihydroguaiaretic acid. The role of alveolar macrophage activation and mediator production.

    OpenAIRE

    Phan, S. H.; Kunkel, S L

    1986-01-01

    The role of alveolar macrophage activation and release of mediators remains unclear. In this study, this role is examined with respect to the effects of relatively selective inhibitors of arachidonate metabolism on the pathogenesis of pulmonary fibrosis. CBA/J mice were administered bleomycin (0.037 units) endotracheally to induce pulmonary fibrosis. Daily intraperitoneal injections of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) inhibited pulmonary fibrosis in a dose-dependent ...

  14. Ferulic acid release and 4-vinylguaiacol formation during brewing and fermentation: indications for feruloyl esterase activity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Coghe, Stefan; Benoot, Koen; Delvaux, Filip; Vanderhaegen, Bart; Delvaux, Freddy R

    2004-02-11

    The release of ferulic acid and the subsequent thermal or enzymatic decarboxylation to 4-vinylguaiacol are inherent to the beer production process. Phenolic, medicinal, or clove-like flavors originating from 4-vinylguaiacol frequently occur in beer made with wheat or wheat malt. To evaluate the release of ferulic acid and the transformation to 4-vinylguaiacol, beer was brewed with different proportions of barley malt, wheat, and wheat malt. Ferulic acid as well as 4-vinylguaiacol levels were determined by HPLC at several stages of the beer production process. During brewing, ferulic acid was released at the initial mashing phase, whereas moderate levels of 4-vinylguaiacol were formed by wort boiling. Higher levels of the phenolic flavor compound were produced during fermentations with brewery yeast strains of the Pof(+) phenotype. In beer made with barley malt, ferulic acid was mainly released during the brewing process. Conversely, 60-90% of ferulic acid in wheat or wheat malt beer was hydrolyzed during fermentation, causing higher 4-vinylguaiacol levels in these beers. As cereal enzymes are most likely inactivated during wort boiling, the additional release of ferulic acid during fermentation suggests the activity of feruloyl esterases produced by brewer's yeast. PMID:14759156

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

    Directory of Open Access Journals (Sweden)

    Jurkić Lela Munjas

    2013-01-01

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

  16. Effect of ca2+ to salicylic acid release in pectin based controlled drug delivery system

    Science.gov (United States)

    Kistriyani, L.; Wirawan, S. K.; Sediawan, W. B.

    2016-01-01

    Wastes from orange peel are potentially be utilized to produce pectin, which are currently an import commodity. Pectin can be used in making edible film. Edible films are potentially used as a drug delivery system membrane after a tooth extraction. Drug which is used in the drug delivery system is salicylic acid. It is an antiseptic. In order to control the drug release rate, crosslinking process is added in the manufacturing of membrane with CaCl2.2H2O as crosslinker. Pectin was diluted in water and mixed with a plasticizer and CaCl2.2H2O solution at 66°C to make edible film. Then the mixture was dried in an oven at 50 °C. After edible film was formed, it was coated using plasticizer and CaCl2.2H2O solution with various concentration 0, 0.015, 0.03 and 0.05g/mL. This study showed that the more concentration of crosslinker added, the slower release of salicylic acid would be. This was indicated by the value of diffusivites were getting smaller respectively. The addition of crosslinker also caused smaller gels swelling value,which made the membrane is mechanically stronger

  17. Controlled release and enhanced antibacterial activity of salicylic acid by hydrogen bonding with chitosan☆

    Institute of Scientific and Technical Information of China (English)

    Zujin Yang; Yanxiong Fang; Hongbing Ji

    2016-01-01

    Microcapsules of salicylic acid (SA) with chitosan were prepared by spray drying method. Various analytical methods were used to characterize the nature of microcapsules. Fourier-transform infrared spectroscopy (FTIR) confirmed the presence of intermolecular interactions between chitosan and SA. Particle size analysis showed that the average size of microcapsules ranged from 2 to 20μm. Scanning electron microscopy (SEM) studies indicated that the microspheres were spherical and had a relatively smooth surface. Microbiological assay of antibacterial activity for SA and its microcapsules was measured using different bacterial strains. It was found that the antibacterial activity of SA was improved after the formation of microcapsules. The in vitro release profile showed that the microcapsules could control SA release from 1 h to 4 h. Kinetic studies revealed that the release pattern follows Korsmeyer–Peppas mechanism. Enhanced antibacterial activity of the SA micro-capsules was attributed to the synergistic effects of intermolecular hydrogen-bonding interactions N–H⋯O and O–H⋯O_C between SA and chitosan. It was also confirmed by quantum chemical calculation.

  18. Sustained Release and Cytotoxicity Evaluation of Carbon Nanotube-Mediated Drug Delivery System for Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

    Full Text Available Carbon nanotubes (CNTs have been widely utilized as a novel drug carrier with promising future applications in biomedical therapies due to their distinct characteristics. In the present work, carboxylic acid-functionalized single-walled carbon nanotubes (f-SWCNTs were used as the starting material to react with anticancer drug, BA to produce f-SWCNTs-BA conjugate via π-π stacking interaction. The conjugate was extensively characterized for drug loading capacity, physicochemical properties, surface morphology, drug releasing characteristics, and cytotoxicity evaluation. The results indicated that the drug loading capacity was determined to be around 20 wt% and this value has been verified by thermogravimetric analysis. The binding of BA onto the surface of f-SWCNTs was confirmed by FTIR and Raman spectroscopies. Powder XRD analysis showed that the structure of the conjugate was unaffected by the loading of BA. The developed conjugate was found to release the drug in a controlled manner with a prolonged release property. According to the preliminary in vitro cytotoxicity studies, the conjugate was not toxic in a standard fibroblast cell line, and anticancer activity was significantly higher in A549 than HepG2 cell line. This study suggests that f-SWCNTs could be developed as an efficient drug carrier to conjugate drugs for pharmaceutical applications in cancer chemotherapies.

  19. Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability

    Directory of Open Access Journals (Sweden)

    Ilaiyaraja Nallamuthu

    2015-06-01

    Full Text Available In this study, chlorogenic acid (CGA, a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of Cmax, longer Tmax, longer MRT, larger AUC0–t and AUC0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

  20. Ethacrynic acid inhibition of histamine release from rat mast cells: effect on cellular ATP levels and thiol groups

    DEFF Research Database (Denmark)

    Johansen, Torben

    1983-01-01

    The experiments concerned the effect of ethacrynic acid (0.5 mM) on the adenosine triphosphate (ATP) content of rat mast cells and the effect on histamine release induced by the ionophore A23187 (10 microM). Ethacrynic acid decreased the ATP level of the cells in presence of antimycin A and glucose...

  1. Studies on in vitro release of CPM from semi-interpenetrating polymer network (IPN) composed of chitosan and glutamic acid

    Indian Academy of Sciences (India)

    K Kumari; P P Kundu

    2008-04-01

    Interpenetrating polymer network (IPN) beads consisting of chitosan–glutamic acid were prepared for in vitro study of controlled release of chlorpheniramine maleate (CPM). A viscous solution of chitosan–glutamic acid was prepared in 2% acetic acid solution, extruded as droplets through a syringe to alkali–methanol solution and the precipitated beads were crosslinked using glutaraldehyde solution. Swelling and drug release studies were carried out. Transport of release medium through the semi-IPN depended upon its pH and extent of crosslinking. The structural and morphological studies of beads were carried out by using a scanning electron microscope (SEM). The larger surface area of beads as well as their ease of handling makes them ideal agents of controlled release.

  2. [Absolute bioavailability of a special sustained-release acetylsalicylic acid formulation].

    Science.gov (United States)

    Lücker, P W; Swoboda, M; Wetzelsberger, N

    1989-03-01

    Absolute Bioavailability of a Special Acetylsalicylic Acid Sustained Release Formulation. The absolute bioavailability of an acetylsalicylic acid (ASA) sustained release formulation (Contrheuma retard), containing 300 mg ASA as initial dose and 350 mg in a retard formulation, was determined in comparison to a standard ASA solution for intravenous administration in a two-treatment, two-period cross-over trial with 6 healthy male volunteers by comparing the areas under the plasma-fluctuation-time curves of the primary metabolite. In addition, it was examined by comparison of the mean times after administration of both formulations, whether the test formulation meets the requirements of a sustained release formulation. The investigations led to the following results: The absolute bioavailability of the test formulation was 95%. The statistical comparison of the areas under the concentration-time courses allowed no decision (neither for equivalence nor difference). The maximal concentration of SA after intravenous administration of the standard formulation was reached after 0.4 h on an average and amounted to 62 micrograms/ml. After oral administration of the test formulation, a mean concentration maximum of 28 micrograms/ml was calculated, which had been reached after about 2 h. The differences are statistically significant. The mean time for SA was 6 h after the standard formulation, whereas after administration of the test compound, a mean of 11.5 h was calculated. 24 h following administration, the concentration of SA was 1.3 micrograms/ml after intravenous administration of the standard formulation and 5.5 micrograms/ml after administration of the test formulation. These differences, too, are statistically significant. From the comparison of the mean time for SA, a retard factor of 1.9 was calculated. PMID:2757664

  3. Release of cetyl pyridinium chloride from fatty acid chelate temporary dental cement

    Science.gov (United States)

    Hurt, Andrew; Coleman, Nichola J.; Tüzüner, Tamer; Bagis, Bora; Korkmaz, Fatih Mehmet; Nicholson, John W.

    2016-01-01

    Abstract Objective To determine whether the antimicrobial nature of a fatty acid chelate temporary dental cement can be enhanced by the addition of 5% cetyl pyridinium chloride (CPC). Materials and methods The temporary cement, Cavex Temporary was employed, and additions of CPC were made to either the base or the catalyst paste prior to mixing the cement. Release of CPC from set cement specimens was followed using reverse-phase HPLC for a period of up to 2 weeks following specimen preparation. Potential interactions between Cavex and CPC were examined by Fourier transform infrared spectroscopy (FTIR) and antimicrobial effects were determined using zone of inhibition measurements after 24 h with disc-shaped specimens in cultured Streptococcus mutans. Results FTIR showed no interaction between CPC and the components of the cement. CPC release was found to follow a diffusion mechanism for the first 6 h or so, and to equilibrate after approximately 2 weeks, with no significant differences between release profiles when the additive was incorporated into the base or the catalyst paste. Diffusion was rapid, and had a diffusion coefficient of approximately 1 × 10−9 m2 s−1 in both cases. Total release was in the range 10–12% of the CPC loading. Zones of inhibition around discs containing CPC were significantly larger than those around the control discs of CPC-free cement. Conclusions The antimicrobial character of this temporary cement can be enhanced by the addition of CPC. Such enhancement is of potential clinical value, though further in vivo work is needed to confirm this. PMID:27335898

  4. Whole Blood Platelet Aggregation and Release Reaction Testing in Uremic Patients

    Directory of Open Access Journals (Sweden)

    Jay Zeck

    2013-01-01

    Full Text Available Background. Platelet function analysis utilizing platelet-rich plasma and optical density based aggregometry fails to identify patients at risk for uremia associated complications. Methods. We employed whole blood platelet aggregation analysis based on impedance as well as determination of ATP release from platelet granules detected by a chemiluminescence method. Ten chronic kidney disease (CKD stage 4 or 5 predialysis patients underwent platelet evaluation. Our study aims to evaluate this platform in this patient population to determine if abnormalities could be detected. Results. Analysis revealed normal aggregation and ATP release to collagen, ADP, and high-dose ristocetin. ATP release had a low response to arachidonic acid (0.37 ± 0.26 nmoles, reference range: 0.6–1.4 nmoles. Platelet aggregation to low-dose ristocetin revealed an exaggerated response (20.9 ± 18.7 ohms, reference range: 0–5 ohms. Conclusions. Whole blood platelet analysis detected platelet dysfunction which may be associated with bleeding and thrombotic risks in uremia. Diminished ATP release to arachidonic acid (an aspirin-like defect in uremic patients may result in platelet associated bleeding. An increased aggregation response to low-dose ristocetin (a type IIb von Willebrand disease-like defect is associated with thrombus formation. This platelet hyperreactivity may be associated with a thrombotic diathesis as seen in some uremic patients.

  5. Encapsulation of gallic acid/cyclodextrin inclusion complex in electrospun polylactic acid nanofibers: Release behavior and antioxidant activity of gallic acid.

    Science.gov (United States)

    Aytac, Zeynep; Kusku, Semran Ipek; Durgun, Engin; Uyar, Tamer

    2016-06-01

    Cyclodextrin-inclusion complexes (CD-ICs) possess great prominence in food and pharmaceutical industries due to their enhanced ability for stabilization of active compounds during processing, storage and usage. Here, CD-IC of gallic acid (GA) with hydroxypropyl-beta-cyclodextrin (GA/HPβCD-IC) was prepared and then incorporated into polylactic acid (PLA) nanofibers (PLA/GA/HPβCD-IC-NF) using electrospinning technique to observe the effect of CD-ICs in the release behavior of GA into three different mediums (water, 10% ethanol and 95% ethanol). The GA incorporated PLA nanofibers (PLA/GA-NFs) were served as control. Phase solubility studies showed an enhanced solubility of GA with increasing amount of HPβCD. The detailed characterization techniques (XRD, TGA and (1)H-NMR) confirmed the formation of inclusion complex between GA and HPβCD. Computational modeling studies indicated that the GA made an efficient complex with HPβCD at 1:1 either in vacuum or aqueous system. SEM images revealed the bead-free and uniform morphology of PLA/GA/HPβCD-IC-NF. The release studies of GA from PLA/GA/HPβCD-IC-NF and PLA/GA-NF were carried out in water, 10% ethanol and 95% ethanol, and the findings revealed that PLA/GA/HPβCD-IC-NF has released much more amount of GA in water and 10% ethanol system when compared to PLA/GA-NF. In addition, GA was released slowly from PLA/GA/HPβCD-IC-NF into 95% ethanol when compared to PLA/GA-NF. It was also observed that electrospinning process had no negative effect on the antioxidant activity of GA when GA was incorporated in PLA nanofibers. PMID:27040215

  6. Enhancement of mononuclear procoagulant activity by platelet 12-hydroxyeicosatetraenoic acid.

    OpenAIRE

    Lorenzet, R; Niemetz, J; Marcus, A J; Broekman, M J

    1986-01-01

    Platelets induce generation of procoagulant tissue factor activity (TFa) by mononuclear leukocytes, and also enhance the TFa induced by endotoxin. Our present investigation demonstrated that arachidonic acid, which by itself had no effect on mononuclear TFa, greatly enhanced platelet-induced TFa. The effect was concentration dependent for both platelets and arachidonate (1-20 microM); other fatty acids tested were inactive. The enhancing effect of arachidonate was more pronounced if platelets...

  7. 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

  8. Swelling and drug release behavior of poly(2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels obtained by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tomic, S.Lj. [Faculty of Technology and Metallurgy, Karnegijeva 4/V, Belgrade (Serbia and Montenegro); Micic, M.M. [Vinca Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia and Montenegro); Filipovic, J.M. [Faculty of Technology and Metallurgy, Karnegijeva 4/V, Belgrade (Serbia and Montenegro); Suljovrujic, E.H. [Vinca Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia and Montenegro)]. E-mail: edin@vin.bg.ac.yu

    2007-05-15

    The new copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) were prepared by gamma irradiation, in order to examine the potential use of these hydrogels in controlled drug release systems. The influence of IA content in the gel on the swelling characteristics and the releasing behavior of hydrogels, and the effect of different drugs, theophylline (TPH) and fenethylline hydrochloride (FE), on the releasing behavior of P(HEMA/IA) matrix were investigated in vitro. The diffusion exponents for swelling and drug release indicate that the mechanisms of buffer uptake and drug release are governed by Fickian diffusion. The swelling kinetics and, therefore, the release rate depends on the matrix swelling degree. The drug release was faster for copolymeric hydrogels with a higher content of itaconic acid. Furthermore, the drug release for TPH as model drug was faster due to a smaller molecular size and a weaker interaction of the TPH molecules with(in) the P(HEMA/IA) copolymeric networks.

  9. Human platelet releasates combined with polyglycolic acid scaffold promote chondrocyte differentiation and phenotypic maintenance

    Indian Academy of Sciences (India)

    Giulia Bernardini; Federico Chellini; Bruno Frediani; Adriano Spreafico; Annalisa Santucci

    2015-03-01

    In the present study, we aimed to demonstrate the differentiating properties of platelet-rich plasma releasates (PRPr) on human chondrocytes seeded on a polygtlycolic acid (PGA) 3D scaffold. Gene expression and biochemical analysis were carried out to assess the improved quality of our PGA-based cartilage constructs supplemented with PRPr. We observed that the use of PRPr as cell cultures supplementation to PGA-chondrocyte constructs may promote chondrocyte differentiation, and thus may contribute to maintaining the chondrogenic phenotype longer than conventional supplementation by increasing high levels of important chondrogenic markers (e.g. sox9, aggrecan and type II collagen), without induction of type I collagen. Moreover, our constructs were analysed for the secretion and deposition of important ECM molecules (sGAG, type II collagen, etc.). Our results indicate that PRPr supplementation may synergize with PGA-based scaffolds to stimulate human articular chondrocyte differentiation, maturation and phenotypic maintenance.

  10. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

    Directory of Open Access Journals (Sweden)

    Hussein MZ

    2011-07-01

    Full Text Available Mohd Zobir Hussein1,2, Samer Hasan Al Ali2, Zulkarnain Zainal2, Muhammad Nazrul Hakim31Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology (ITMA, 2Department of Chemistry, Faculty of Science, 3Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: An ellagic acid (EA–zinc layered hydroxide (ZLH nanohybrid (EAN was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8′ position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host–guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA.Keywords: ellagic acid, nonaqueous solution, ZnO, zinc-layered hydroxide, viability test

  11. Doxorubicin hydrochloride-oleic acid conjugate loaded nanostructured lipid carriers for tumor specific drug release.

    Science.gov (United States)

    Zhao, Shuangni; Minh, Le Van; Li, Na; Garamus, Vasil M; Handge, Ulrich A; Liu, Jianwen; Zhang, Rongguang; Willumeit-Römer, Regine; Zou, Aihua

    2016-09-01

    The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment. PMID:27137808

  12. Noble Gases and Nitrogen Released from a Lunar Soil Pyroxene Separate by Acid Etching

    Science.gov (United States)

    Rider, P. E.

    1993-07-01

    We report initial results from a series of experiments designed to measure recently implanted solar wind (SW) ions in lunar soil mineral grains [1]. An acid-etching technique similar to the CSSE method developed at ETH Zurich was used to make abundance and isotope measurements of the SW noble gas and nitrogen compositions. Among the samples examined was a pyroxene separate from soil 75081. It was first washed with H2O to remove contamination from the sample finger walls and grain surfaces. H2O also acted as a weak acid, releasing gases from near-surface sites. Treatment with H2SO3 followed the water washes. Acid pH (~1.8 to ~1.0) and temperature (~23 degrees C to ~90 degrees C) and duration of acid attack (several minutes to several days) were varied from step to step. Finally, the sample was pyrolyzed in several steps to remove the remaining gases, culminating with a high-temperature pyrolysis at 1200 degrees C. Measurements of the light noble gases were mostly consistent with those from previous CSSE experiments performed on pyroxene [2,3]. It should be noted, however, that the Zurich SEP component was not easily distinguishable in the steps where it was expected to be observed. We suspect our experimental protocol masked the SEP reservoir, preventing us from seeing its distinctive signature. The most interesting results from this sample are its Kr and Xe isotopic and elemental compositions. Pyroxene apparently retains heavy noble gases as well as ilmenite (and plagioclase [4]). The heavy noble gas element ratios from this sample along with those previously reported [5,6] are, however, considerably heavier than the theoretically determined "solar system" values [7,8]. Explanations for the difference include the possibility that the derivations are incorrect, that there is another component of lunar origin mixing with the solar component, or that some type of loss mechanism is altering the noble gas reservoirs of the grains. The Kr and Xe isotopic compositions for

  13. Non-dioxin-like polychlorinated biphenyls induce a release of arachidonic acid in liver epithelial cells: A partial role of cytosolic phospholipase A2 and extracellular signal-regulated kinases 1/2 signalling

    Czech Academy of Sciences Publication Activity Database

    Umannová, Lenka; Neča, J.; Andrysík, Zdeněk; Vondráček, Jan; Upham, B. L.; Trosko, J.E.; Hofmanová, Jiřina; Kozubík, Alois; Machala, M.

    2008-01-01

    Roč. 247, č. 1 (2008), s. 55-60. ISSN 0300-483X R&D Projects: GA ČR(CZ) GA524/05/0595 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : polychlorinated biphenyls * aryl hydrocarbon receptor * genotoxicity Subject RIV: BO - Biophysics Impact factor: 2.836, year: 2008

  14. Fast Release of Sulfosalicylic Acid from Polymer Implants Consisting of Regenerated Cellulose/γ-Ferric Oxide/Polypyrrole

    OpenAIRE

    Nargis A. Chowdhury; John Robertson; Ahmed Al-Jumaily; Ramos, Maximiano V.

    2014-01-01

    This work presents a comparative study on the rate of drug release from implantable matrices induced by electric and magnetic fields separately for better biomedical applications. The matrices were prepared by coating γ-ferric oxide dispersed regenerated cellulose film by polypyrrole doped with sulfosalicylic acid as an anti-inflammatory drug. The drug release mechanisms were studied under both the electric and the magnetic fields separately in an acetate buffer solution with pH 5.5 and tempe...

  15. Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles.

    Science.gov (United States)

    Pandey, Sanjeev K; Patel, Dinesh K; Maurya, Akhilendra K; Thakur, Ravi; Mishra, Durga P; Vinayak, Manjula; Haldar, Chandana; Maiti, Pralay

    2016-08-01

    Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton's lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17-30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer. PMID:27112980

  16. Xanthurenic acid distribution, transport, accumulation and release in the rat brain.

    Science.gov (United States)

    Gobaille, Serge; Kemmel, Véronique; Brumaru, Daniel; Dugave, Christophe; Aunis, Dominique; Maitre, Michel

    2008-05-01

    Tryptophan metabolism through the kynurenine pathway leads to several neuroactive compounds, including kynurenic and picolinic acids. Xanthurenic acid (Xa) has been generally considered as a substance with no physiological role but possessing toxic and apoptotic properties. In the present work, we present several findings which support a physiological role for endogenous Xa in synaptic signalling in brain. This substance is present in micromolar amounts in most regions of the rat brain with a heterogeneous distribution. An active vesicular synaptic process inhibited by bafilomycin and nigericin accumulates xanthurenate into pre-synaptic terminals. A neuronal transport, partially dependant on adenosine 5'-triphosphate (ATP), sodium and chloride ions exists in NCB-20 neurons which could participate in the clearance of extracellular xanthurenate. Both transports (neuronal and vesicular) are greatly enhanced by the presence of micromolar amounts of zinc ions. Finally, electrical in vivo stimulation of A10-induced Xa release in the extracellular spaces of the rat prefrontal cortex. This phenomenon is reproduced by veratrine, K+ ions and blocked by EGTA and tetrodotoxin. These results strongly argue for a role for Xa in neurotransmission/neuromodulation in the rat brain, thus providing the existence of specific Xa receptors. PMID:18182052

  17. Enantioselective changes in oxidative stress and toxin release in Microcystis aeruginosa exposed to chiral herbicide diclofop acid

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Jing [School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418 (China); MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Natural Research and Environmental Sciences, Zhejiang University, Hangzhou 310058 (China); Zhang, Ying [Department of Environmental Science, East China Normal University, Shanghai 200241 (China); Chen, Shengwen [School of Urban Development and Environment Engineering, Shanghai Second Polytechnic University, Shanghai 201209 (China); Liu, Chaonan; Zhu, Yongqiang [School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418 (China); Liu, Weiping, E-mail: wliu@zju.edu.cn [MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Natural Research and Environmental Sciences, Zhejiang University, Hangzhou 310058 (China)

    2014-01-15

    Highlights: •The first study on enantioselective oxidative stress and toxin release from Microcystis aeruginosa. •Provide information for the R-enantiomer poses more oxidative stress than the S-enantiomer. •Lifecycle analysis of chiral pollutants needs more attention in environmental assessment. -- Abstract: Enantioselective oxidative stress and toxin release from Microcystis aeruginosa after exposure to the chiral herbicide diclofop acid were investigated. Racemic diclofop acid, R-diclofop acid and S-diclofop acid induced reactive oxygen species (ROS) generation, increased the concentration of malondialdehyde (MDA), enhanced the activity of superoxide dismutase (SOD) and triggered toxin release in M. aeruginosa to varying degrees. The increase in MDA concentration and SOD activity in M. aeruginosa occurred sooner after exposure to diclofop acid than when the cyanobacteria was exposed to either the R- and the S-enantiomer. In addition, enantioselective toxicity of the enantiomers was observed. The R-enantiomer trigged more ROS generation, more SOD activity and more toxin synthesis and release in M. aeruginosa cells than the S-enantiomer. Diclofop acid and its R-enantiomer may collapse the transmembrane proton gradient and destroy the cell membrane through lipid peroxidation and free radical oxidation, whereas the S-enantiomer did not demonstrate such action. R-diclofop acid inhibits the growth of M. aeruginosa in the early stage, but ultimately induced greater toxin release, which has a deleterious effect on the water column. These results indicate that more comprehensive study is needed to determine the environmental safety of the enantiomers, and application of chiral pesticides requires more direct supervision and training. Additionally, lifecycle analysis of chiral pollutants in aquatic system needs more attention to aide in the environmental assessment of chiral pesticides.

  18. Enantioselective changes in oxidative stress and toxin release in Microcystis aeruginosa exposed to chiral herbicide diclofop acid

    International Nuclear Information System (INIS)

    Highlights: •The first study on enantioselective oxidative stress and toxin release from Microcystis aeruginosa. •Provide information for the R-enantiomer poses more oxidative stress than the S-enantiomer. •Lifecycle analysis of chiral pollutants needs more attention in environmental assessment. -- Abstract: Enantioselective oxidative stress and toxin release from Microcystis aeruginosa after exposure to the chiral herbicide diclofop acid were investigated. Racemic diclofop acid, R-diclofop acid and S-diclofop acid induced reactive oxygen species (ROS) generation, increased the concentration of malondialdehyde (MDA), enhanced the activity of superoxide dismutase (SOD) and triggered toxin release in M. aeruginosa to varying degrees. The increase in MDA concentration and SOD activity in M. aeruginosa occurred sooner after exposure to diclofop acid than when the cyanobacteria was exposed to either the R- and the S-enantiomer. In addition, enantioselective toxicity of the enantiomers was observed. The R-enantiomer trigged more ROS generation, more SOD activity and more toxin synthesis and release in M. aeruginosa cells than the S-enantiomer. Diclofop acid and its R-enantiomer may collapse the transmembrane proton gradient and destroy the cell membrane through lipid peroxidation and free radical oxidation, whereas the S-enantiomer did not demonstrate such action. R-diclofop acid inhibits the growth of M. aeruginosa in the early stage, but ultimately induced greater toxin release, which has a deleterious effect on the water column. These results indicate that more comprehensive study is needed to determine the environmental safety of the enantiomers, and application of chiral pesticides requires more direct supervision and training. Additionally, lifecycle analysis of chiral pollutants in aquatic system needs more attention to aide in the environmental assessment of chiral pesticides

  19. Omega-3 Fatty Acids and Inflammatory Processes

    Directory of Open Access Journals (Sweden)

    Philip C. Calder

    2010-03-01

    Full Text Available Long chain fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or at least associated with, changes in fatty acid composition of cell membranes. Changes in these compositions can modify membrane fluidity, cell signaling leading to altered gene expression, and the pattern of lipid mediator production. Cell involved in the inflammatory response are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the n-3 fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these often have differing properties from those of arachidonic acid-derived eicosanoids. EPA and DHA give rise to newly discovered resolvins which are anti-inflammatory and inflammation resolving. Increased membrane content of EPA and DHA (and decreased arachidonic acid content results in a changed pattern of production of eicosanoids and resolvins. Changing the fatty acid composition of cells involved in the inflammatory response also affects production of peptide mediators of inflammation (adhesion molecules, cytokines etc.. Thus, the fatty acid composition of cells involved in the inflammatory response influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 PUFAs suggest that they may be useful as therapeutic agents in disorders with an inflammatory component.

  20. Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

    DEFF Research Database (Denmark)

    Wensaas, Andreas J; Rustan, Arild C; Just, Marlene;

    2008-01-01

    Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these...... processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA......), whereas release of beta-oxidation products was unchanged at baseline, but significantly increased with respect to control myotubes after preincubation with TTA and EPA. Preincubation with TTA enhanced both complete (CO(2)) and beta-oxidation of PA, whereas EPA increased only beta-oxidation significantly...

  1. Preparation and in vitro evaluation of carboxymethylated κ-carrageenan aluminum hydrogel microbeads for prolonged release of mefenamic acid

    International Nuclear Information System (INIS)

    Polymers that swell in an aqueous medium have been widely used to formulate controlled-release dosage forms. This study aims to prepare carboxymethyl κ-carrageenan (CMKC) microbeads and evaluate its potential for controlled release of mefenamic acid in comparison to the positive control, carboxymethylcellulose (CMC) microbeads. The powdered κ-carrageenan was carboxymethylated and Fourier-Transform Infrared Spectroscopy confirmed the carboxy methylation. Aqueous solutions of CMC (3% w/v) and CMKC (3%, 4%, 5% w/v) were prepared as microbeads using ionotropic gelation technique. Microbeads were loaded with mefenamic acid by suspending it in the aqueous solution (0.5% w/v) of the drug for 72 hours. Particle size and surface morphology were characterized using scanning electron microscopy. One-way ANOVA was used to determine a significant difference between the release activity of the drug-loaded CMKC and CMC microbeads. Differential Scanning Calorimetry was performed on the drug, drug- free, and drug-loaded microbeads of CMC and CMKC. Two-way ANOVARM showed significant interaction in % drug release of the three groups being analyzed in respect to time effect (p≤0.001) and group effect (p≤0.001). Post Hoc Duncan Multiple Range Test showed that 3% CMC and 4% CMKC has equal average % drug release values and is significantly higher compared to the commercial mefenamic acid. Also, one way ANOVA showed that 3% CMC was able to release the drug with no significant difference in time (p = 0.159), while 4% CMKC (p < 0.001) and the commercial mefenamic acid (p≤0.001) were able to release the drug with significant difference in time (author)

  2. Comparison of alkali treatments for efficient release of p-coumaric acid and enzymatic saccharification of sorghum pith.

    Science.gov (United States)

    Jiang, Kankan; Li, Lulu; Long, Liangkun; Ding, Shaojun

    2016-05-01

    Two separate temperature and time ranges were respectively conducted for optimizing release of p-coumaric acid and enzymatic saccharification of sorghum pith by NaOH pretreatment using response surface methodology. Two desirable pretreatment conditions were selected as follows: 37°C, 2% NaOH and 12h, and 100°C, 1.75% NaOH and 37min in the low and high temperature ranges, respectively. Under these conditions, the enzymatic glucose yields were 85.6% and 90.4% respectively, whereas p-coumaric acid yields were 95.1% and 98.1% respectively. The final recovery of esterified p-coumaric acid reached 82.8% and 87.4% respectively after further separation with HP-20 resin. Interestingly, strong linear correlations exist between p-coumaric acid release with glucan saccharification yield and lignin dissolution. These results indicate that sorghum pith could be an attractive source for natural p-coumaric acid and efficient release of p-coumaric acid and enzymatic saccharification of sorghum pith can be achieved by mild NaOH pretreatment. PMID:26868149

  3. Baclofen (β-p-chlorophenyl-γ-aminobutyric acid) enhances [3H]γ-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro

    International Nuclear Information System (INIS)

    The rat globus pallidus has been investigated as a possible model in which to study pre-synaptic GABA mechanisms in vitro. (+ -)-Baclofen (300μM-1 mM) significantly enhanced the release of radioactivity from superfused slices of rat globus pallidus prelabelled with 3H-GABA in vitro. This releasing action was specific to the (+)-isomer of baclofen. Neither the (-)-isomer nor another neuronal depressant DL-α-upsilon-diaminopimelic acid had any significant effect. The releasing effect of baclofen appeared unrelated to the phenethylamine moiety of its structure as neither β-phenethylamine nor dopamine evoked release of 3H-GABA from pallidal slices. Baclofen increased the efflux of radioactivity from pallidal slices prelabelled with either [3H]β-alanine or 3H diaminobutric acid in vitro. The use of specific glial and neuronal GABA uptake blocking compounds (β-alanine and (+ -)-cis-1,3-aminocyclohexanecarboxylic acid) did not permit resolution of the elements from which baclofen was evoking [3H]GABA release. Baclofen also inhibited uptake of [3H]GABA into pallidal slices with an IC50 value of 6 x 10-4m. The GABA-like properties of baclofen may be related to the (+)-isomer while non-specific neuronal depressant actions are an effect of the (-)-isomer. The potential of the (+)-isomer as an antipyschotic agent while (-)-baclofen remains the effective antispastic drug free from unwanted side-effects is discussed. (author)

  4. pH-responsive deoxyribonucleic acid capture/release by polydopamine functionalized magnetic nanoparticles

    International Nuclear Information System (INIS)

    Highlights: • PDA@Fe3O4 were prepared and applied for efficient extraction of DNA from pathogens. • The DNA capture and release by PDA@Fe3O4 was pH-induced. • The adsorption capacity of PDA@Fe3O4 for DNA was 161 mg g−1. • PDA@Fe3O4 based MSPE was combined with PCR and CE for rapid detection of pathogens. - Abstract: Polydopamine functionalized magnetic nanoparticles (PDA@Fe3O4) were prepared and characterized by transmission electron microscopy, scanning electron microscopy, zeta potential and vibrating sample magnetometry. They were found to enable highly efficient capture of genomic deoxyribonucleic acid (DNA). The adsorption capacity of PDA@Fe3O4 for genomic DNA can reach 161 mg g−1. The extraction protocol used aqueous solutions for DNA binding to and releasing from the surface of the magnetic particles based on the pH inducing the charge switch of amino and phenolic hydroxyl groups on PDA@Fe3O4. The extracted DNA with high quality (A260/A280 = 1.80) can be directly used as templates for polymerase chain reaction (PCR) followed by capillary electrophoresis (CE) analysis. None of the toxic chemical reagents and PCR inhibitors was used throughout the whole procedure. PDA@Fe3O4 based magnetic solid phase extraction (MSPE) method was superior to those using commercial kit and traditional phenol–chloroform extraction methods in yield of DNA. The developed PDA@Fe3O4 based MSPE-PCR-CE method was applied for simultaneous and fast detection of Listeria monocytogenes and Escherichia coli O157:H7 in milk

  5. pH-responsive deoxyribonucleic acid capture/release by polydopamine functionalized magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu; Ma, Xiangdong; Ding, Chun; Jia, Li, E-mail: jiali@scnu.edu.cn

    2015-03-03

    Highlights: • PDA@Fe{sub 3}O{sub 4} were prepared and applied for efficient extraction of DNA from pathogens. • The DNA capture and release by PDA@Fe{sub 3}O{sub 4} was pH-induced. • The adsorption capacity of PDA@Fe{sub 3}O{sub 4} for DNA was 161 mg g{sup −1}. • PDA@Fe{sub 3}O{sub 4} based MSPE was combined with PCR and CE for rapid detection of pathogens. - Abstract: Polydopamine functionalized magnetic nanoparticles (PDA@Fe{sub 3}O{sub 4}) were prepared and characterized by transmission electron microscopy, scanning electron microscopy, zeta potential and vibrating sample magnetometry. They were found to enable highly efficient capture of genomic deoxyribonucleic acid (DNA). The adsorption capacity of PDA@Fe{sub 3}O{sub 4} for genomic DNA can reach 161 mg g{sup −1}. The extraction protocol used aqueous solutions for DNA binding to and releasing from the surface of the magnetic particles based on the pH inducing the charge switch of amino and phenolic hydroxyl groups on PDA@Fe{sub 3}O{sub 4}. The extracted DNA with high quality (A{sub 260}/A{sub 280} = 1.80) can be directly used as templates for polymerase chain reaction (PCR) followed by capillary electrophoresis (CE) analysis. None of the toxic chemical reagents and PCR inhibitors was used throughout the whole procedure. PDA@Fe{sub 3}O{sub 4} based magnetic solid phase extraction (MSPE) method was superior to those using commercial kit and traditional phenol–chloroform extraction methods in yield of DNA. The developed PDA@Fe{sub 3}O{sub 4} based MSPE-PCR-CE method was applied for simultaneous and fast detection of Listeria monocytogenes and Escherichia coli O157:H7 in milk.

  6. Fast Release of Sulfosalicylic Acid from Polymer Implants Consisting of Regenerated Cellulose/γ-Ferric Oxide/Polypyrrole

    Directory of Open Access Journals (Sweden)

    Nargis A. Chowdhury

    2014-01-01

    Full Text Available This work presents a comparative study on the rate of drug release from implantable matrices induced by electric and magnetic fields separately for better biomedical applications. The matrices were prepared by coating γ-ferric oxide dispersed regenerated cellulose film by polypyrrole doped with sulfosalicylic acid as an anti-inflammatory drug. The drug release mechanisms were studied under both the electric and the magnetic fields separately in an acetate buffer solution with pH 5.5 and temperature 37°C during a period of 5 hours. The amount of drug released was analysed by UV-Vis spectrophotometry. The mechanism of drug release from the matrices under electric field includes expansion of conductive polymer chain and the electrostatic force between electron and drug. The drug release mechanism from the matrices under magnetic field is based on the fact that the heat produced locally by magnetic particles loosens the polymer (polypyrrole chain surrounding the particles. As a result, the drugs attached to the polypyrrole chain come out to the release medium. The matrices showed fast release of drug, that is, more than 60% of the loaded drug was released within 1 h, and are ideal for the treatment of illness in an emergency care.

  7. Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

    DEFF Research Database (Denmark)

    Kofod, Hans; Lernmark, A; Hedeskov, C J

    1986-01-01

    Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L-phenyl...

  8. Peptides released from acid goat whey by a yeast-lactobacillus association isolated from cheese microflora.

    Science.gov (United States)

    Didelot, Sandrine; Bordenave-Juchereau, Stephanie; Rosenfeld, Eric; Piot, Jean-Marie; Sannier, Frederic

    2006-05-01

    Seven lactobacilli and a variety of microflora extracted from twenty five commercial cheeses were grown on unsupplemented acid goat whey and screened for their capacity to hydrolyse whey proteins [alpha-lactalbumin (alpha-la) and beta-lactoglobulin (beta-lg)] and to generate peptides. Fermentations were performed aerobically or anaerobically at 37 degrees C using crude or pre-heated whey (10 min at 65, 75 or 85 degrees C). Under aerobic conditions, growth of lactobacilli was poor and protein hydrolysis did not occur. Anaerobic conditions slightly increased lactobacilli growth but neither beta-lg hydrolysis nor peptide generation were observed. More than 50% of alpha-la was digested into a truncated form of alpha-la (+/- 12 kDa) in crude whey and whey pre-heated at 65 degrees C. Twenty-five microflora extracted from raw milk cheeses were screened for their proteolytic activities on acid goat whey under the conditions previously described. Eight of them were able to hydrolyse up to 50% of alpha-la mainly during aerobic growth on crude or pre-heated whey. The corresponding hydrolysates were enriched in peptides. The hydrolysate involving microflora extracted from Comté cheese after or at 18 months ripening was the only one to exhibit hydrolysis of both alpha-la and beta-lg. Microbiological analysis showed that microorganisms originating from Comté cheese and capable of growth on unsupplemented whey consisted of Candida parapsilosis and Lactobacillus paracasei. Fermentation kinetic profiles suggested that peptides were released from alpha-la hydrolysis. The co-culture of both microorganisms was required for alpha-la hydrolysis that occurred concomitantly with the pH decrease. During whey fermentation, Cand. parapsilosis excrete at least one protease responsible for alpha-la hydrolysis, and Lb. paracasei is responsible for medium acidification that is required for protease activation. PMID:16476172

  9. Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines

    Science.gov (United States)

    Pessione, Enrica; Cirrincione, Simona

    2016-01-01

    Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the main nitrogen compounds produced by LAB are considered. Besides biogenic amines derived from the amino acids tyrosine, histidine, phenylalanine, lysine, ornithine, and glutamate by decarboxylation, interesting peptides can be decrypted by the proteolytic activity of LAB. LAB proteolytic system is very efficient in releasing encrypted molecules from several proteins present in different food matrices. Alpha and beta-caseins, albumin and globulin from milk and dairy products, rubisco from spinach, beta-conglycinin from soy and gluten from cereals constitute a good source of important bioactive compounds. These encrypted peptides are able to control nutrition (mineral absorption and oxidative stress protection), metabolism (blood glucose and cholesterol lowering) cardiovascular function (antithrombotic and hypotensive action), infection (microbial inhibition and immunomodulation) and gut-brain axis (opioids and anti-opioids controlling mood and food intake). Very recent results underline the role of food-encrypted peptides in protein folding (chaperone-like molecules) as well as in cell cycle and apoptosis control, suggesting new and positive aspects of fermented food, still unexplored. In this context, the detailed (transcriptomic, proteomic, and metabolomic) characterization of LAB of food interest (as starters, biocontrol agents, nutraceuticals, and probiotics) can supply a solid evidence-based science to support beneficial effects and it is a promising approach as well to obtain

  10. Lesions of nucleus accumbens affect morphine-induced release of ascorbic acid and GABA but not of glutamate in rats.

    Science.gov (United States)

    Sun, Ji Y; Yang, Jing Y; Wang, Fang; Wang, Jian Y; Song, Wu; Su, Guang Y; Dong, Ying X; Wu, Chun F

    2011-10-01

    Our previous studies have shown that local perfusion of morphine causes an increase of extracellular ascorbic acid (AA) levels in nucleus accumbens (NAc) of freely moving rats. Lines of evidence showed that glutamatergic and GABAergic were associated with morphine-induced effects on the neurotransmission of the brain, especially on the release of AA. In the present study, the effects of morphine on the release of extracellular AA, γ-aminobutyric acid (GABA) and glutamate (Glu) in the NAc following bilateral NAc lesions induced by kainic acid (KA) were studied by using the microdialysis technique, coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD) and fluorescent detection (HPLC-FD). The results showed that local perfusion of morphine (100 µM, 1 mM) in NAc dose-dependently increased AA and GABA release, while attenuated Glu release in the NAc. Naloxone (0.4 mM) pretreated by local perfusion to the NAc, significantly blocked the effects of morphine. After NAc lesion by KA (1 µg), morphine-induced increase in AA and GABA were markedly eliminated, while decrease in Glu was not affected. The loss effect of morphine on AA and GABA release after KA lesion could be recovered by GABA agonist, musimol. These results indicate that morphine-induced AA release may be mediated at least by µ-opioid receptor. Moreover, this effect of morphine possibly depend less on the glutamatergic afferents, but more on the GABAergic circuits within this nucleus. Finally, AA release induced by local perfusion of morphine may be GABA-receptor mediated and synaptically localized in the NAc. PMID:20731632

  11. Metabolically Engineered Fungal Cells With Increased Content Of Polyunsaturated Fatty Acids

    DEFF Research Database (Denmark)

    2008-01-01

    This invention relates to the production of fatty acids and particularly to the production of the polyunsaturated fatty acids (PUFAs) arachidonic acid (ARA) and eicosapentaenoic acid (EPA) in genetically engineered fungal cells, in particular, to metabolically engineered Saccharomyces cerevisiae...

  12. The Salicylic Acid-Mediated Release of Plant Volatiles Affects the Host Choice of Bemisia tabaci.

    Science.gov (United States)

    Shi, Xiaobin; Chen, Gong; Tian, Lixia; Peng, Zhengke; Xie, Wen; Wu, Qingjun; Wang, Shaoli; Zhou, Xuguo; Zhang, Youjun

    2016-01-01

    The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) causes serious crop losses worldwide by transmitting viruses. We have previously shown that salicylic acid (SA)-related plant defenses directly affect whiteflies. In this study, we applied exogenous SA to tomato plants in order to investigate the interaction between SA-induced plant volatiles and nonviruliferous B. tabaci B and Q or B- and Q-carrying tomato yellow leaf curl virus (TYLCV). The results showed that exogenous SA caused plants to repel nonviruliferous whiteflies, but the effect was reduced when the SA concentration was low and when the whiteflies were viruliferous. Exogenous SA increased the number and quantity of plant volatiles-especially the quantity of methyl salicylate and δ-limonene. In Y-tube olfactometer assays, methyl salicylate and δ-limonene repelled the whiteflies, but the repellency was reduced for viruliferous Q. We suggest that the release of plant volatiles as mediated by SA affects the interaction between whiteflies, plants, and viruses. Further studies are needed to determine why viruliferous Q is less sensitive than nonviruliferous Q to repellent plant volatiles. PMID:27376280

  13. Dynamic modeling of in vitro lipid digestion: individual fatty acid release and bioaccessibility kinetics.

    Science.gov (United States)

    Giang, T M; Gaucel, S; Brestaz, P; Anton, M; Meynier, A; Trelea, I C; Le Feunteun, S

    2016-03-01

    The aim of this study was to gain knowledge about the role of triacylglycerol (TAG) composition in fatty acids (FA) of o/w emulsions on both the pancreatic lipolysis kinetics and the bioaccessibility of released products (i.e. contained within the bile salt micellar phase). A mathematical model was developed and its predictions were compared to a set of experimental data obtained during an in vitro digestion of a whey protein stabilized emulsion. Modeling results show that FA residues of TAG were hydrolyzed at specific rates, inducing different bioaccessibility kinetics. The estimated lipolysis rate constants of the studied FA (C8:0, C10:0≫C18:1 n-9≫C12:0>C14:0>C16:0≈C16:1 n-7>C22:6 n-3) were in close agreement with the available literature on the substrate specificity of pancreatic lipase. Results also suggest that lipolysis products are very rapidly solubilized in the bile salt mixed micelles with no fractionation according to the FA carbon chain. PMID:26471670

  14. Macroporous chitosan hydrogels: Effects of sulfur on the loading and release behaviour of amino acid-based compounds.

    Science.gov (United States)

    Elviri, Lisa; Asadzadeh, Maliheh; Cucinelli, Roberta; Bianchera, Annalisa; Bettini, Ruggero

    2015-11-01

    Chitosan is a biodegradable, biocompatible polymer of natural origin widely applied to the preparation of functional hydrogels suitable for controlled release of drugs, peptides and proteins. Non-covalent interactions, expecially ionic interactions, are the main driver of the loading and release behaviour of amino acids or peptides from chitosan hydrogels. With the aim to improve the understanding of the mechanisms governing the behaviour of chitosan hydrogels on peptide uptake and delivery, in this paper the attention was focused on the role played by sulfur on the interactions of chitosan hydrogels with sulfur-containing amino acids (AA) and peptides. Hence, loading and release experiments on cysteine, cystine and glutathione (SH containing amino acid, dipeptide and tripeptide, respectively) as well as on glycine and valine as apolar amino acids were carried out. For these puroses, chitosan hydrogels were prepared in an easy and reproducible manner by a freeze-gelation process on a poly-L-lysine coated support. The hydrogel surface pore size, uniformity and distribution were tested. Optimal results (D50 = 26 ± 4 μm) were obtained by using the poly-L-lysine positively-charged surface. The loading results gathered evidenced that the sulfur-containing molecules presented an increased absorption both in terms of rate and extent by chitosan hydrogels with respect to nonpolar amino acids, mainly due to ionic and hydrogen bond interactions. ATR-FTIR analysis carried out on chitosan hydrogels, with and without the AA related compounds to study putative interactions, supported these apparent sulfur-dependent results. Finally, chitosan hydrogels displayed excellent retention capabilities (AA release <5%) for all AA, strongly supporting the use of chitosan hydrogels as matrix for controlled drug release. PMID:26256323

  15. Novel fenofibric acid-loaded controlled release pellet bioequivalent to choline fenofibrate-loaded commercial product in beagle dogs.

    Science.gov (United States)

    Kim, Kyung Soo; Jin, Sung Giu; Mustapha, Omer; Yousaf, Abid Mehmood; Kim, Dong Wuk; Kim, Young Hun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2015-07-25

    The objective of this study was to develop a novel fenofibric acid-loaded controlled release pellet showing enhanced, or equivalent to, bioavailability compared with two commercially available products containing fenofibrate or choline fenofibrate. The effect of solubilizing agents on drug solubility and the impact of fillers on core properties were investigated. Among them, magnesium carbonate most improved drug solubility, and κ-carrageenan provided the best spherical cores. The fenofibric acid-loaded pellet was prepared with magnesium carbonate and κ-carrageenan employing the extrusion/spheronizing technique followed by coating with ethylcellulose. Furthermore, dissolution and pharmacokinetic study in beagle dogs were performed compared to the fenofibrate-loaded commercial tablet (FCT) and choline fenofibrate-loaded commercial mini-tablet (CFCM). This fenofibric acid-loaded pellet showed controlled release of the drug in phosphate buffer (pH 6.8) and 0.025 M sodium laurylsulfate within 4h. Furthermore, this pellet and CFCM exhibited similar dissolution profiles. Plasma concentrations greater than 1,000 ng/ml were maintained from 30 min to 8h, suggesting a sustained release pattern. Also, the fenofibric acid-loaded pellet gave significantly higher AUC and Cmax values than FCT, indicating that it improved the bioavailability of fenofibrate due to enhanced solubility and sustained release. In addition, this pellet and CFCM were not significantly different in terms of pharmacokinetic parameters including AUC, Cmax and Tmax. Thus, this pellet was bioequivalent to CFCM in beagle dogs. In conclusion, this fenofibric acid-loaded controlled release pellet would be a potential alternative to the choline fenofibrate-loaded commercial product. PMID:26024820

  16. Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Tan, Huaping, E-mail: hptan@njust.edu.cn [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Hu, Xiaohong [School of Material Engineering, Jinling Institute of Technology, Nanjing (China)

    2015-11-01

    A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion.

  17. Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug.

    Science.gov (United States)

    Zhang, Wuxia; Dong, Dongqi; Li, Peng; Wang, Dongdong; Mu, Haibo; Niu, Hong; Duan, Jinyou

    2016-03-30

    Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72 h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72 h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability. PMID:26794949

  18. Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

    International Nuclear Information System (INIS)

    A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion

  19. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease

    OpenAIRE

    1992-01-01

    Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-1ADA-infected monocytes cocultur...

  20. Castor oil increases intestinal formation of platelet-activating factor and acid phosphatase release in the rat.

    OpenAIRE

    Pinto, A; Calignano, A; Mascolo, N; Autore, G; Capasso, F

    1989-01-01

    1. When castor oil was administered by gavage to rats, the duodenum and jejunum but not ileum and colon produced large amounts (5-6 fold greater than control) of platelet activating factor (Paf). 2. Intraluminal release of acid phosphatase (AP) was also markedly increased (5-6 fold greater than control) in the duodenum and jejunum of castor oil-treated rats and there was a correlation between the elevated release of AP and intestinal hyperaemia. 3. These findings support a role for Paf as a m...

  1. Regional selectivity of a gamma-aminobutyric acid-induced (/sup 3/H)acetylcholine release sensitive to inhibitors of gamma-aminobutyric acid uptake

    Energy Technology Data Exchange (ETDEWEB)

    Bonanno, G.; Raiteri, M.

    1987-05-01

    The effects of gamma-aminobutyric acid (GABA) on the release of (/sup 3/H)acetylcholine ((/sup 3/H)ACh) were studied in synaptosomes prepared from rat hippocampus, cerebral cortex, hypothalamus, and striatum and prelabelled with (/sup 3/H)choline. When synaptosomes were exposed in superfusion to exogenous GABA (0.01-0.3 mM) the basal release of newly synthesized (/sup 3/H)ACh was increased in a concentration-dependent way in hippocampus, cortex, and hypothalamus nerve endings. In contrast, the release of (/sup 3/H)ACh was not significantly affected by GABA in striatal synaptosomes. The effect of GABA was not antagonized significantly by bicuculline or picrotoxin. Muscimol caused only a slight not significant increase of (/sup 3/H)ACh release when tested at 0.3 mM whereas, at this concentration, (-)-baclofen was totally inactive. The GABA-induced release of (/sup 3/H)ACh was counteracted by SKF 89976A, SKF 100561, and SKF 100330A, three strong and selective GABA uptake inhibitors. The data suggest that, in selective areas of the rat brain, GABA causes release of (/sup 3/H)ACh following penetration into cholinergic nerve terminals through a GABA transport system.

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Directory of Open Access Journals (Sweden)

    C. v. Sperber

    2015-03-01

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

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

    Science.gov (United States)

    Lubkowski, Krzysztof; Smorowska, Aleksandra; Grzmil, Barbara; Kozłowska, Agnieszka

    2015-03-18

    The preparation and characterization of a controlled-release multicomponent (NPK) fertilizer with the coating layer consisting of a biodegradable copolymer of poly(butylene succinate) and a butylene ester of dilinoleic acid (PBS/DLA) is reported. The morphology and structure of the resulting polymer-coated materials and the thickness of the covering layers were examined using X-ray diffraction and scanning electron microscopy coupled with energy dispersive X-ray analysis. The mechanical properties of these materials were determined with a strength-testing machine. Nutrient release was measured in water using spectrophotometry, potentiometry, and conductivity methods. The results of the nutrient release experiments from these polymer-coated materials were compared with the requirements for controlled-release fertilizers. A conceptual model is presented describing the mechanism of nutrient release from the materials prepared in this study. This model is based on the concentrations of mineral components inside the water-penetrated fertilizer granules, the diffusion properties of the nutrients in water, and a diffusion coefficient through the polymer layer. The experimental kinetic data on nutrient release were interpreted using the sigmoidal model equation developed in this study. PMID:25715823

  5. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid in Simulated Intestinal Fluids.

    Directory of Open Access Journals (Sweden)

    Patrik Knöös

    Full Text Available A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium or fed state (FeSSIF. The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

  6. Efficient inhibition of heavy metal release from mine tailings against acid rain exposure by triethylenetetramine intercalated montmorillonite (TETA-Mt).

    Science.gov (United States)

    Gong, Beini; Wu, Pingxiao; Huang, Zhujian; Li, Yuanyuan; Yang, Shanshan; Dang, Zhi; Ruan, Bo; Kang, Chunxi

    2016-11-15

    The potential application of triethylenetetramine intercalated montmorillonite (TETA-Mt) in mine tailings treatment and AMD (acid mine drainage) remediation was investigated with batch experiments. The structural and morphological characteristics of TETA-Mt were analyzed with XRD, FTIR, DTG-TG and SEM. The inhibition efficiencies of TETA-Mt against heavy metal release from mine tailings when exposed to acid rain leaching was examined and compared with that of triethylenetetramine (TETA) and Mt. Results showed that the overall inhibition by TETA-Mt surpassed that by TETA or Mt for various heavy metal ions over an acid rain pH range of 3-5.6 and a temperature range of 25-40°C. When mine tailings were exposed to acid rain of pH 4.8 (the average rain pH of the mining site where the mine tailings were from), TETA-Mt achieved an inhibition efficiency of over 90% for Cu(2+), Zn(2+), Cd(2+) and Mn(2+) release, and 70% for Pb(2+) at 25°C. It was shown that TETA-Mt has a strong buffering capacity. Moreover, TETA-Mt was able to adsorb heavy metal ions and the adsorption process was fast, suggesting that coordination was mainly responsible. These results showed the potential of TETA-Mt in AMD mitigation, especially in acid rain affected mining area. PMID:27450331

  7. Drying of micro-encapsulated lactic acid bacteria — Effects of trehalose and immobilization on cell survival and release properties

    Science.gov (United States)

    Li, Xiaoyan; Chen, Xiguang

    2009-03-01

    Lactic acid bacteria (LAB) were encapsulated with alginate, gelatin and trehalose additives by the extrusion method and dried at 4 °C. The microcapsules were generally spherical and had a wrinkled surface with a size of 1.7 mm ± 0.2 mm. Trehalose as a carbohydrate source in the culture medium could reduce acid production and performed no function in the positive proliferation of LAB. Using trehalose as a carbohydrate source and protective medium simultaneously had a benefit in the protection of LAB cells during the storage at 4 °C. The density of live LAB cells could be 107 CFU g-1 after 8 weeks of storage. Cells of LAB could be continuously released from the capsules from the acidic (pH 1.2) to neutral conditions (pH 6.8). The release amounts and proliferation speeds of LAB cells in neutral medium were much larger and faster than those in acidic conditions. Additionally, immobilization of LAB could improve the survival of cells when they were exposed to acidic medium (pH 1.2) with a survival rate of 76 %.

  8. Drying of Micro-Encapsulated Lactic Acid Bacteria-Effects of Trehalose and Immobilization on Cell Survival and Release Properties

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoyan; CHEN Xiguang

    2009-01-01

    Lactic acid bacteria (LAB) were encapsulated with alginate, gelatin and trehalose additives by the extrusion method and dried at 4℃. The microcapsules were generally spherical and had a wrinkled surface with a size of 1.7mm±0.2mm. Trehalose as a carbohydrate source in the culture medium could reduce acid production and performed no function in the positive proliferation of LAB. Using trehalose as a carbohydrate source and protective medium simultaneously had a benefit in the protection of LAB cells during the storage at 4℃. The density of hve LAB cells could be 10- CFU g-1 after 8 weeks of storage. Cells of LAB could be con-tinuously released from the capsules from the acidic (pH 1.2) to neutral conditions (plt 6.8). The release amounts and proliferation speeds of LAB cells in neutral medium were much larger and faster than those m acidic conditions. Additionally, immobilization of LAB could improve the survival of cells when they, were exposed to acidic medium (pH 1.2) with a survival rate of 76 %.

  9. In vitro dissolution study of acetylsalicylic acid solid dispersions. Tunable drug release allowed by the choice of polymer matrix

    Czech Academy of Sciences Publication Activity Database

    Policianová, Olivia; Brus, Jiří; Hrubý, Martin; Urbanová, Martina

    2015-01-01

    Roč. 20, č. 8 (2015), s. 935-940. ISSN 1083-7450 R&D Projects: GA ČR(CZ) GA14-03636S; GA ČR GPP106/11/P426 Grant ostatní: AV ČR(CZ) M200501201 Institutional support: RVO:61389013 Keywords : acetylsallicylic acid * controlled drug release * polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.202, year: 2014

  10. Controlled 5-fluorouracil release from hydrogels of Poly (acrylamide-co-metacrylic acid) crosslinked by means Of gamma irradiation techniques

    International Nuclear Information System (INIS)

    This report present the results on entrapped a cytostatic 5-Fluorouracil (5-F) in polymeric matrixes named hydrogels of polyacrylamide co -metacrylic acid crosslinked by means of gamma radiation with doses of 10,30, and 30 kGy at 25 o C. The drug delivery was followed by HPLC. The behavior of 5 -Fu migration from polymeric network was analyze by Iguchi equation for plain structure systems. The diffusion coefficients were obtained and drug release was in accordance with Fickian behavior

  11. Controlled release of diclofenac sodium from pH-responsive carrageenan-g-poly(acrylic acid) superabsorbent hydrogel

    Indian Academy of Sciences (India)

    Hossein Hosseinzadeh

    2010-07-01

    In this paper, controlled release of diclofenac sodium (DS) from pH-sensitive carrageenan-gpoly(acrylic acid) superabsorbent hydrogels was investigated. The hydrogels were prepared by graft copolymerization of acrylic acid (AA) onto kappa-carrageenan, using ammonium persulfate (APS) as a free radical initiator in the presence of methylene bisacrylamide (MBA) as a crosslinker. Infrared spectroscopy was carried out to confirm the chemical structure of the hydrogel. Moreover, morphology of the samples was examined by scanning electron microscopy (SEM). The synthesized hydrogels were subjected to equilibrium swelling studies in simulated gastric and intestinal fluids (SGF and SIF). Hydrogels containing drug DS, at different drug-to-polymer ratios, were prepared by direct adsorption method. The loading yield was found to depend on both the impregnation time and the amount of encapsulated drug. In vitro drug-release studies in different buffer solutions showed that the most important parameter affecting the drug-release behaviour of hydrogels is the pH of the solution. The mechanism involved in release was Fickian ( ≤ 0.43, = 0.348) and Super Case II kinetics ( > 1, = 1.231) at pH 1.2 and 7.4, respectively.

  12. Acid-independent release of secretin and cholecystokinin by intraduodenal infusion of fat in humans.

    Science.gov (United States)

    Rhodes, R A; Skerven, G; Chey, W Y; Chang, T M

    1988-01-01

    In order to clarify a possible role of fat content in the release of secretin and cholecystokinin by liquid nutritional supplements in humans, duodenal pH and plasma concentrations of secretin and cholecystokinin were studied during the intraduodenal infusion of Ensure, Vivonex, 10% Intralipid, and sodium oleate. Significant release of secretin was observed with Intralipid and sodium oleate, while significant release of cholecystokinin was observed with all four testing solutions. Duodenal pH was rarely below 4.5 during the infusion of Ensure, Intralipid, and sodium oleate. Duodenal pH was high, greater than 6.0, when plasma secretin and cholecystokinin levels were elevated during the administration of Ensure, Intralipid, and sodium oleate. We conclude that both secretin and cholecystokinin are released in response to fat solutions in the duodenum and that low duodenal pH was not responsible for either secretin or cholecystokinin release during intraduodenal infusions of Ensure, Intralipid, or sodium oleate. PMID:3140233

  13. Extracellular ATP stimulates exocytosis via localized Ca(2+) release from acidic stores in rat pancreatic beta cells.

    Science.gov (United States)

    Xie, Li; Zhang, Ming; Zhou, Wei; Wu, Zhengxing; Ding, Jiuping; Chen, Liangyi; Xu, Tao

    2006-04-01

    Three different methods, membrane capacitance (C(m)) measurement, amperometry and FM dye labeling were used to investigate the role of extracellular ATP in insulin secretion from rat pancreatic beta cells. We found that extracellular application of ATP mobilized intracellular Ca(2+) stores and synchronously triggered vigorous exocytosis. No influence of ATP on the readily releasable pool of vesicles was observed, which argues against a direct modulation of the secretory machinery at a level downstream of Ca(2+) elevation. The stimulatory effects of ATP were greatly reduced by intracellular perfusion of BAPTA but not EGTA, suggesting a close spatial association of fusion sites with intracellular Ca(2+) releasing sites. ATP-induced Ca(2+) transients and exocytosis were not blocked by thapsigargin (TG), by a ryanodine receptor antagonist or by dissipation of pH in acidic stores by monensin alone, but they were greatly attenuated by IP(3) receptor inhibition as well as ionomycin plus monensin, suggesting involvement of IP(3)-sensitive acidic Ca(2+) stores. Taken together, our data suggest that extracellular ATP triggers exocytosis by mobilizing spatially limited acidic Ca(2+) stores through IP(3) receptors. This mechanism may explain how insulin secretion from the pancreas is coordinated through diffusible ATP that is co-released with insulin. PMID:16536741

  14. Monohydroxamic acids and bridging dihydroxamic acids as chelators to ruthenium(III) and as nitric oxide donors: syntheses, speciation studies and nitric oxide releasing investigations.

    Science.gov (United States)

    Griffith, Darren; Krot, Krystyna; Comiskey, Jedd; Nolan, Kevin B; Marmion, Celine J

    2008-01-01

    The synthesis and spectroscopic characterisation of novel mononuclear Ru(III)(edta)(hydroxamato) complexes of general formula [Ru(H2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-C1 and 3-Me-phenylhydroxamato), as well as the first example of a Ru(III)-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)].H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear Ru(III) complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(mu-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with Ru(III), are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru(III) involves initial formation of Ru(III)-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of Ru(III)-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids. PMID:18399240

  15. Preparation and Characterization of Kynurenic Acid Occluded in Sol-Gel Silica and SBA-15 Silica as Release Reservoirs

    Directory of Open Access Journals (Sweden)

    Tessy López

    2014-01-01

    Full Text Available Kynurenic acid (KYNA may have important therapeutic effects in neurological disorders; however, its use as a neuroprotective agent is restricted due to its very limited ability to cross the blood brain barrier (BBB. For this reason, we are looking for new alternatives for KYNA to reach the brain; one of them is using drug delivery systems. To obtain KYNA release reservoirs, KYNA molecules were hosted in two different silica materials. The different KYNA-silica materials were characterized by means of several physical techniques. The spectroscopic studies showed that KYNA molecules remained unchanged once hosted in silica materials. The surface area values of KYNA-silica samples were substantially lower than those for pure silica materials due to the addition of the drug. The electronic micrographs showed that the sol-gel KYNA-silica material consisted of aggregates of nanoparticles around 50 nm in size. On the other hand, the typical SBA-15 hexagonal arrangement was observed, even when hosting KYNA molecules. KYNA release profiles, carried out during approximately 300 hours, showed a first stage of fast drug release followed by a slow release phase. The experimental values fitted to the Peppas equation indicate that the release mechanism was controlled by Fickian diffusion.

  16. Phospholipase A2 and 3H-hemicholinium-3 binding sites in rat brain: A potential second-messenger role for fatty acids in the regulation of high-affinity choline uptake

    International Nuclear Information System (INIS)

    The involvement of phospholipase A2 (PLA2) and fatty acid release in the regulation of sodium-dependent high-affinity choline uptake in rat brain was assessed in vitro through the use of the specific binding of 3H-hemicholinium-3 (3H-HCh-3). Addition of arachidonic acid and other unsaturated fatty acids to rat striatal membranes in vitro resulted in a dose-dependent, temperature-independent activation of 3H-HCh-3 binding. Scatchard analysis revealed that these changes in binding result from a 2-fold increase in the affinity and capacity of 3H-HCh-3 binding. Saturated fatty acids, lysophospholipids, and phospholipids did not affect specific 3H-HCh-3 binding. Addition of defatted BSA to membranes, which had been treated previously with arachidonic acid, completely reversed the increase in specific 3H-HCh-3 binding. However, several inhibitors of fatty acid metabolism, including nordihydroguaiaretic acid, indomethacin, catalase, and superoxide dismutase, did not alter arachidonic acid-induced changes in 3H-HCh-3 binding, suggesting that unsaturated fatty acids, and not their metabolites, are directly responsible for the observed activation of specific 3H-HCh-3 binding. Additionally, unsaturated fatty acids dose-dependently inhibited high-affinity 3H-choline uptake in rat striatal synaptosomes, apparently due to the disruption of synaptosomal integrity. The phospholipase A2 inhibitors quinacrine hydrochloride, trifluoperazine, and 4-bromophenacylbromide dose-dependently inhibited potassium depolarization-induced activation of specific 3H-HCh-3 binding in slices of rat brain in vitro. Similarly, both quinacrine and trifluoperazine inhibited the metabolism of phospholipids and the release of fatty acids evoked by either elevated KCl or calcium ionophore A23187

  17. Caffeic Acid Phenethyl Ester: Consequences of Its Hydrophobicity in the Oxidative Functions and Cytokine Release by Leukocytes

    Directory of Open Access Journals (Sweden)

    Luana Chiquetto Paracatu

    2014-01-01

    Full Text Available Numerous anti-inflammatory properties have been attributed to caffeic acid phenethyl ester (CAPE, an active component of propolis. NADPH oxidases are multienzymatic complexes involved in many inflammatory diseases. Here, we studied the importance of the CAPE hydrophobicity on cell-free antioxidant capacity, inhibition of the NADPH oxidase and hypochlorous acid production, and release of TNF-α and IL-10 by activated leukocytes. The comparison was made with the related, but less hydrophobic, caffeic and chlorogenic acids. Cell-free studies such as superoxide anion scavenging assay, triene degradation, and anodic peak potential (Epa measurements showed that the alterations in the hydrophobicity did not provoke significant changes in the oxidation potential and antiradical potency of the tested compounds. However, only CAPE was able to inhibit the production of superoxide anion by activated leukocytes. The inhibition of the NADPH oxidase resulted in the blockage of production of hypochlorous acid. Similarly, CAPE was the more effective inhibitor of the release of TNF-α and IL-10 by Staphylococcus aureus stimulated cells. In conclusion, the presence of the catechol moiety and the higher hydrophobicity were essential for the biological effects. Considering the involvement of NADPH oxidases in the genesis and progression of inflammatory diseases, CAPE should be considered as a promising anti-inflammatory drug.

  18. Hyaluronic acid induces the release of growth factors from platelet-rich plasma

    Directory of Open Access Journals (Sweden)

    Kohei Iio

    2016-04-01

    Conclusion: The levels of growth factors released by PRP on Day 5 were increased by the addition of HA. A mixture of PRP and HA may be a more effective therapy than PRP or HA alone for osteoarthritis and tendinopathy.

  19. Madhucosides A and B, protobassic acid glycosides from Madhuca indica with inhibitory activity on free radical release from phagocytes.

    Science.gov (United States)

    Pawar, Rahul S; Bhutani, K K

    2004-04-01

    The structures of madhucosides A (1) and B (2), isolated from the bark of Madhuca indica, were established as 3-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranosyl-28-O-[beta-D-xylopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1-->4)]-beta-D-glucopyranosyl(1--> 3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl]protobassic acid and 3-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranosyl-28-O-[beta-D-xylopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1-->4)]-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl]protobassic acid, respectively. These two compounds showed significant inhibitory effects on both superoxide release from polymorphonuclear cells in a NBT reduction assay and hypochlorous acid generation from neutrophils assessed in a luminol-enhanced chemiluminescence assay. PMID:15104500

  20. Carboxylic Acid Ionophores as Probes of the Role of Calcium in Biological Systems

    Science.gov (United States)

    Reed, P. W.

    1983-01-01

    The biological effects of calcium ionophores are described, focusing on arachidonic acid oxygenation, and the formation of a number of oxygenated metabolites of arachidonic acid. These metabolites are involved in a number of bodily functions, and their production may be regulated by calcium.

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

    International Nuclear Information System (INIS)

    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 [14C]arachidonate to [14C]5-hydroperoxyeicosatetraenoic acid (HPETE) and [14C]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 Ca2+- and ATP-dependent. For both enzyme activities, the CA2+ 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

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

    Science.gov (United States)

    Taghipour, Marzieh; Jalali, Mohsen

    2016-07-01

    In this study, batch experiments were conducted to investigate the effects of nanoparticles (NPs) (MgO, ZnO, TiO2) and clay minerals (bentonite, zeolite) on the release of chromium (Cr) from leather factory waste (LFW) and LFW treated soil using organic acids. Chromium release from all treatments was studied in the presence of citric acid, oxalic acid and CaCl2 solutions. The results showed that, in all treatments, organic acids released more Cr than inorganic salt (CaCl2). The release of Cr by citric acid was higher than that by oxalic acid. In LFW treated soil and LFW, the release of Cr from the all treatments with NPs was less than that from the clay mineral treatments. On the other hand, in the presence of organic acids, Cr release by NPs and clay minerals decreased. Two kinetic models including pseudo-first- and pseudo-second-order model were tested to describe the time dependent Cr release data. Among the kinetic models used, the pseudo-second-order model generally gave the best fits to experimental data. Before and after release experiments, Cr in LFW, treated LFW, control soil and LFW treated soils were fractionated. In all treatments, the greatest amounts of Cr were found in the residual fraction (RES). The organic acids were effective in reducing the exchangeable (EXC), bound to organic matter (OM) and bound to carbonate (CAR) fractions of Cr in all treatments, whereas, after release of Cr from treated soils, Cr remained mainly in the RES fraction. The application of NPs and clay minerals in soil led to a significant transformation of Cr from mobile fractions to the RES fraction. Therefore, organic ligands played a dominant role in mobility and bioavailability of Cr and the removal of Cr by adsorbents. PMID:27139119

  3. SYNTHESIS AND IN VITRO CHARACTERIZATION OF HYDROXYPROPYL METHYLCELLULOSE-GRAFT-POLY (ACRYLIC ACID/2-ACRYLAMIDO-2-METHYL-1-PROPANESULFONIC ACID) POLYMERIC NETWORK FOR CONTROLLED RELEASE OF CAPTOPRIL.

    Science.gov (United States)

    Furqan Muhammad, Iqbal; Mahmood, Ahmad; Aysha, Rashid

    2016-01-01

    A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension. PMID:27008813

  4. β-lactam antibiotic-induced release of lipoteichoic acid from Staphylococcus aureus leads to activation of neutrophil granulocytes

    Directory of Open Access Journals (Sweden)

    Hartung Thomas

    2006-06-01

    Full Text Available Abstract Background Polymorphonuclear neutrophil granulocytes (PMN are phagocytes of the first line of antimicrobial defense. Previously we demonstrated that lipoteichoic acid (LTA from Staphylococcus aureus (S. aureus directly activates neutrophil granulocytes. Others have reported that exposure of S. aureus to β-lactam antibiotics leads to LTA release. In the present study we addressed the question whether exposure of S. aureus to β-lactam antibiotics or antibiotics of other groups results in the generation of PMN-stimulating activity and whether this activity can be attributed to LTA. Methods S. aureus were exposed to flucloxacillin, a β-lactam antibiotic or to the protein synthesis-inhibitors erythromycin and gentamicin, or to ciprofloxacin, a gyrase inhibitor. Supernatants of the antibiotic-treated bacteria were assayed for their LTA content and for their effect on PMN functions. Results We observed that exposure of S. aureus to flucloxacillin and, to a lesser degree to ciprofloxacin, but not to erythromycin or gentamicin led to LTA release. Co-incubation of neutrophil granulocytes with LTA-containing supernatants led to PMN activation as assed by morphological changes, release of IL-8, delay of spontaneous apoptosis and enhanced phagocytic activity. Depletion of LTA from the supernatants markedly reduced their PMN-activating capacity. Conclusion The findings suggest that, via the activation of PMN, antibiotic-induced LTA release from S. aureus leads to enhanced antimicrobial activity of the innate immune defense mechanisms.

  5. Uranium pollution in an estuary affected by pyrite acid mine drainage and releases of naturally occurring radioactive materials

    International Nuclear Information System (INIS)

    Highlights: → Huelva estuary is affected by former phosphogypsum releases and pyrite acid mine drainage. → Time evolution of uranium concentration is analyzed after halting of NORM releases. → Two new contamination sources are preventing the complete uranium cleaning: (1) The leaching of phosphogypsum stacks located close to Tinto River. (2) Pyrite acid mine drainage. → High uranium concentrations are dissolved in water and precipitate subsequently. - Abstract: After the termination of phosphogypsum discharges to the Huelva estuary (SW Spain), a unique opportunity was presented to study the response of a contaminated environmental compartment after the cessation of its main source of pollution. The evolution over time of uranium concentrations in the estuary is presented to supply new insights into the decontamination of a scenario affected by Naturally Occurring Radioactive Material (NORM) discharges. The cleaning of uranium isotopes from the area has not taken place as rapidly as expected due to leaching from phosphogypsum stacks. An in-depth study using various techniques of analysis, including 234U/238U and 230Th/232Th ratios and the decreasing rates of the uranium concentration, enabled a second source of uranium contamination to be discovered. Increased uranium levels due to acid mine drainage from pyrite mines located in the Iberian Pyrite Belt (SW Spain) prevent complete uranium decontamination and, therefore, result in levels nearly twice those of natural background levels.

  6. Studies of manufacturing controlled-release graphene acid and catalyzing synthesis of chalcone with Claisen-Schmidt condensation reaction

    Science.gov (United States)

    Li, Jihui; Feng, Jia; Li, Mei; Wang, Qiaolian; Su, Yumin; Jia, Zhixin

    2013-07-01

    In the paper, graphene acid (GA) was manufactured, using flake graphite as raw material, and the acidity and the structure of GA were characterized as well as. Then, chalcone was synthesized in the presence of GA, using acetophenone and benzaldehyde as the reactant. The results showed that the acidity of GA was for pH = 1.12 in aqueous solution, and it was structured by the graphene sheets with the spaces between the graphene sheet and the graphene sheet and sulfuric acid (H2SO4) and acetic acid (CH3CO2H) inside the spaces. At the same time, the results also exhibited that the chalcone yield was able to reach 60.36% when GA dosage was 5 g, and the chalcone yields could attain apart 60.36, 52.05 and 31.16% when 5 g of GA was used thrice. This shows that GA is not only a high-performance catalyst, but also a controlled-release catalyst.

  7. Membrane Disruption by Antimicrobial Fatty Acids Releases Low-Molecular-Weight Proteins from Staphylococcus aureus

    OpenAIRE

    Parsons, Joshua B; Yao, Jiangwei; Frank, Matthew W.; Jackson, Pamela; Rock, Charles O

    2012-01-01

    The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward Gram-positive bacteria. A screen of fatty acids as growth inhibitors of Staphylococcus aureus revealed structure-specific antibacterial activity. Fatty acids like oleate (18:1Δ9) were nontoxic, whereas palmitoleate (16:1Δ9) was a potent growth inhibitor. Cells treated with 16:1Δ9 exhibited rapid membrane depolarization, the disruption of all major branches of macromolecular synthes...

  8. Excitatory amino acid antagonists and endogenous aspartate and glutamate release from rat hippocampal slices.

    OpenAIRE

    Connick, J. H.; Stone, T. W.

    1988-01-01

    1. The effect of excitatory amino acid agonists and antagonists on the efflux of endogenous aspartate and glutamate from the rat hippocampus in vitro was studied. 2. None of the compounds tested had any effect on the basal efflux of endogenous aspartate and glutamate. 3. 2-Amino-5-phosphonovaleric acid (APV), 2-amino-7-phosphonoheptanoic acid (APH) and MK-801 all reduced the potassium-evoked efflux of aspartate and glutamate by between 14.9% and 34.3% (P less than 0.05). 4. The depression of ...

  9. Preparation and controlled-release studies of a protocatechuic acid-magnesium/aluminum-layered double hydroxide nanocomposite

    Directory of Open Access Journals (Sweden)

    Barahuie F

    2013-05-01

    Full Text Available Farahnaz Barahuie,1 Mohd Zobir Hussein,1 Samer Hasan Hussein-Al-Ali,2 Palanisamy Arulselvan,3 Sharida Fakurazi,3,4 Zulkarnain Zainal11Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, 4Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, MalaysiaAbstract: In the study reported here, magnesium/aluminum (Mg/Al-layered double hydroxide (LDH was intercalated with an anticancer drug, protocatechuic acid, using ion-exchange and direct coprecipitation methods, with the resultant products labeled according to the method used to produce them: “PANE” (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the ion-exchange method and “PAND” (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the direct method, respectively. Powder X-ray diffraction and Fourier transform infrared spectroscopy confirmed the intercalation of protocatechuic acid into the inter-galleries of Mg/Al-LDH. The protocatechuic acid between the interlayers of PANE and PAND was found to be a monolayer, with an angle from the z-axis of 8° for PANE and 15° for PAND. Thermogravimetric and differential thermogravimetric analysis results revealed that the thermal stability of protocatechuic acid was markedly enhanced upon intercalation. The loading of protocatechuic acid in PANE and PAND was estimated to be about 24.5% and 27.5% (w/w, respectively. The in vitro release study of protocatechuic acid from PANE and PAND in phosphate-buffered saline at pH 7.4, 5.3, and 4.8 revealed that the nanocomposites had a sustained release property. After 72 hours incubation of PANE and PAND with MCF-7 human breast cancer and HeLa human cervical cancer cell lines, it was found that the nanocomposites had suppressed the growth of these cancer cells

  10. Poly(anhydride-ester) and Poly(N-vinyl-2-pyrrolidone) Blends: Salicylic acid-releasing blends with hydrogel-like properties that reduce inflammation

    OpenAIRE

    Ouimet, Michelle A.; Fogaça, Renata; Snyder, Sabrina S; Sathaye, Sameer; Luiz H. Catalani; Pochan, Darrin J.; Uhrich, Kathryn E.

    2014-01-01

    Polymers such as poly(N-vinyl-2-pyrrolidone) (PVP) have been used to prepare hydrogels for wound dressing applications but are not inherently bioactive. For enhanced healing, the release of physically admixed therapeutics from hydrogels has been evaluated, but with limited control over drug release profiles. To overcome these limitations, PVP was blended with salicylic acid-based poly(anhydride-esters) (SAPAE) and shown to exhibit hydrogel properties upon swelling. In vitro release studies de...

  11. Controlled release of linalool using nanofibrous membranes of poly(lactic acid) obtained by electrospinning and solution blow spinning: A comparative study

    Science.gov (United States)

    The controlled-release of natural plant oils such as linalool is of interest in therapeutics, cosmetics, and antimicrobial and larvicidal products. The present study reports the release characteristics of linalool encapsulated at three concentrations (10, 15 and 20 wt.%) in poly(lactic acid) nanofib...

  12. Reproductive Biology of Selaginella: I. Determination of Megasporangia by 2-Chloroethylphosphonic Acid, an Ethylene-releasing Compound.

    Science.gov (United States)

    Brooks, K E

    1973-04-01

    Control clumps of Selaginella wallacei Heiron., sprayed with distilled water with Tween 20, produced a high proportion of microsporangia. Similar clumps sprayed with 2-chlorethyl-phosphonic acid, and ethylene-releasing compound (Ethephon), at 7.65 and 76.5 mg/liter produced almost exclusively megasporangia. Treatment of Selaginella pallescens (Presl) Spring with Ethephon at 34 mg/liter caused the production of megasporangia in the microsporangiate files of the strobili. The possibility that ethylene may be involved in the regulation of heterospory in Selaginella is discussed. PMID:16658398

  13. THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE

    OpenAIRE

    Morawin, B.; Turowski, D; Naczk, M.; Siatkowski, I.; Zembron-Lacny, A.

    2014-01-01

    The generation of reactive nitrogen/oxygen species (RN/OS) represents an important mechanism in erythropoietin (EPO) expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric ...

  14. Mechanism of cAMP-induced H+ -efflux of Dictyostelium cells: a role for fatty acids

    Indian Academy of Sciences (India)

    H Flaadt; R Schaloske; D Malchow

    2000-09-01

    Aggregating Dictyostelium cells release protons when stimulated with cAMP. To find out whether the protons are generated by acidic vesicles or in the cytosol, we permeabilized the cells and found that this did not alter the cAMP-response. Proton efflux in intact cells was inhibited by preincubation with the V-type H+ ATPase inhibitor concanamycin A and with the plasma membrane H+ ATPase blocker miconazole. Surprisingly, miconazole also inhibited efflux in permeabilized cells, indicating that this type of H+ ATPase is present on intracellular vesicles as well. Vesicular acidification was inhibited by miconazole and by concanamycin A, suggesting that the acidic vesicles contain both V-type and P-type H+ ATPases. Moreover, concanamycin A and miconazole acted in concert, both in intact cells and in vesicles. The mechanism of cAMP-induced Ca2+-fluxes involves phospholipase A2 activity. Fatty acids circumvent the plasma membrane and stimulate vesicular Ca2+-efflux. Here we show that arachidonic acid elicited H+-efflux not only from intact cells but also from acidic vesicles. The target of regulation by arachidonic acid seemed to be the vesicular Ca2+-relase channel.

  15. Polymer system for controlled drug delivery and release of all-trans retinoic acid

    Czech Academy of Sciences Publication Activity Database

    Lidický, Ondřej; Šírová, Milada; Etrych, Tomáš

    Tel Aviv : International Cancer Microenvironment Society, 2015. P-87. [International Conference on Tumor Microenvironment: Progression, Therapy & Prevention /7./. 11.10.2015-15.10.2015, Tel Aviv] R&D Projects: GA ČR(CZ) GAP301/11/0325 Institutional support: RVO:61389013 ; RVO:61388971 Keywords : drug delivery systems * pH-controlled release * HPMA copolymers Subject RIV: CD - Macromolecular Chemistry; FD - Oncology ; Hematology (MBU-M)

  16. Slow release anti-fungal skin formulations based on citric acid intercalated layered double hydroxides nanohybrids

    OpenAIRE

    Perera, Jayoda; Weerasekera, Manjula; Kottegoda, Nilwala

    2015-01-01

    Background During the past few decades, the occurrence of superficial fungal infections has rapidly increased. As the fungal infections take longer time to get cured, concepts such as designing drugs with extended persistence and controlled release have gained attention. In this context, nanotechnology has been identified as the latest technological revolution which has opened up new pathways for designing new therapeutic materials. Out of the many available nano-structures layered double hyd...

  17. Formulation, in-vitro release and transdermal diffusion of alpha-lipoic acid / Tizane Snyman

    OpenAIRE

    Snyman, Tizane

    2009-01-01

    Acne is a common disease characterised by follicular hyperkeratinisation, bacterial hipercolonisation as well as immune reactions and inflammation. In acne, reactive oxygen species (ROS) may be released from the damaged follicular walls, which could cause the advancement of inflammation in the pathogenesis of the disease. The topical application of antioxidants is a promising approach to support the endogenous antioxidant defence and avoid oxidative injury that may lead to acne. The skin ...

  18. Gustducin couples fatty acid receptors to GLP-1 release in colon

    OpenAIRE

    LI Yan; Kokrashvili, Zaza; Mosinger, Bedrich; Margolskee, Robert F.

    2013-01-01

    Sweet taste receptor subunits and α-gustducin found in enteroendocrine cells of the small intestine have been implicated in release of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in response to glucose and noncaloric sweeteners. α-Gustducin has also been found in colon, although its function there is unclear. We examined expression of α-gustducin, GLP-1, and GIP throughout the intestine. The number of α-gustducin-expressing cell...

  19. Kinetic energy releases of small amino acids upon interaction with keV ions

    International Nuclear Information System (INIS)

    In chromatin, DNA is tightly packed into one complex together with histone and non-histone proteins. These proteins are known to protect the DNA against indirect and to some extent even direct radiation damage. Radiation action upon amino acids is thus one of the primary steps in biological radiation action. In this paper we investigate the ionization and fragmentation of the gas-phase amino acids glycine, alanine and valine upon interaction with keV α-particles. High resolution coincidence time-of-flight mass spectrometry is used to determine the dominant fragmentation channels as well as fragment kinetic energies. (authors)

  20. Kinetic energy releases of small amino acids upon interaction with keV ions

    Energy Technology Data Exchange (ETDEWEB)

    Bari, S.; Alvarado, F.; Postma, J.; Sobocinski, P.; Hoekstra, R.; Schlatholter, T. [Groningen Univ., KVI Atomic Physics (Netherlands); Schlatholter, T. [Universites P. et M. Curie and D. Diderot, INSP, CNRS UMR 75-88, 75 - Paris (France)

    2009-01-15

    In chromatin, DNA is tightly packed into one complex together with histone and non-histone proteins. These proteins are known to protect the DNA against indirect and to some extent even direct radiation damage. Radiation action upon amino acids is thus one of the primary steps in biological radiation action. In this paper we investigate the ionization and fragmentation of the gas-phase amino acids glycine, alanine and valine upon interaction with keV {alpha}-particles. High resolution coincidence time-of-flight mass spectrometry is used to determine the dominant fragmentation channels as well as fragment kinetic energies. (authors)

  1. Effect of fatty acids on leukocyte function

    Directory of Open Access Journals (Sweden)

    Pompéia C.

    2000-01-01

    Full Text Available Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization.

  2. Preparation and evaluation of a linoleic-acid-modified amphiphilic polypeptide copolymer as a carrier for controlled drug release

    International Nuclear Information System (INIS)

    In the present study, we describe the synthesis, characterization and self-assembly of a novel amphiphilic linoleic acid (LA)-modified polypeptide copolymer and its drug release behavior in vitro as well. Initially, an amphiphilic ABA triblock copolymer comprising polytetrahydrofuran (PTHF) as a central hydrophobic block and poly(L-lysine)s as outer hydrophilic blocks was prepared via the ring-opening polymerization of ε-benzyloxycarbonyl-L-lysine N-carboxyanhydride with a distal amine-terminated PTHF as a macroinitiator, followed by the removal of the protecting group. The resulting triblock copolymer was then reacted with linoleic acid in the presence of N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl)/N-hydroxysuccinimide (HOSu) to give rise to a target LA-modified polypeptide copolymer. It was found to self-assemble into nanoparticles in water. Its critical aggregation concentration was assessed by fluorescence measurement with N-phenyl-1-naphthylamine employed as a molecular probe. The particle sizes of the aggregates were determined by dynamic light scattering, and the aggregate morphologies were evidenced by transmission electron microscopy measurements. Finally, the drug-loading capacity and release behavior in vitro were investigated by using doxorubicin as a model drug.

  3. Differential activation of acid sphingomyelinase and ceramide release determines invasiveness of Neisseria meningitidis into brain endothelial cells.

    Directory of Open Access Journals (Sweden)

    Alexander Simonis

    2014-06-01

    Full Text Available The interaction with brain endothelial cells is central to the pathogenicity of Neisseria meningitidis infections. Here, we show that N. meningitidis causes transient activation of acid sphingomyelinase (ASM followed by ceramide release in brain endothelial cells. In response to N. meningitidis infection, ASM and ceramide are displayed at the outer leaflet of the cell membrane and condense into large membrane platforms which also concentrate the ErbB2 receptor. The outer membrane protein Opc and phosphatidylcholine-specific phospholipase C that is activated upon binding of the pathogen to heparan sulfate proteoglycans, are required for N. meningitidis-mediated ASM activation. Pharmacologic or genetic ablation of ASM abrogated meningococcal internalization without affecting bacterial adherence. In accordance, the restricted invasiveness of a defined set of pathogenic isolates of the ST-11/ST-8 clonal complex into brain endothelial cells directly correlated with their restricted ability to induce ASM and ceramide release. In conclusion, ASM activation and ceramide release are essential for internalization of Opc-expressing meningococci into brain endothelial cells, and this segregates with invasiveness of N. meningitidis strains.

  4. Fabrication of a bioadhesive transdermal device from chitosan and hyaluronic acid for the controlled release of lidocaine.

    Science.gov (United States)

    Anirudhan, T S; Nair, Syam S; Nair, Anoop S

    2016-11-01

    A novel efficient transdermal (TD) lidocaine (LD) delivery device based on chitosan (CS) and hyaluronic acid (HA) was successfully developed in the present investigation. CS was grafted with glycidyl methacrylate (GMA) and butyl methacrylate (BMA) to fabricate a versatile material with improved adhesion and mechanical properties. HA was hydrophobically modified by covalently conjugating 3-(dimethylamino)-1-propylamine (DMPA) to encapsulate poorly water soluble LD and was uniformly dispersed in modified CS matrix. The prepared materials were characterized through FTIR, NMR, XRD, SEM, TEM and tensile assay. The dispersion of amine functionalized HA (AHA) on modified CS matrix offered strong matrix - filler interaction, which improved the mechanical properties and drug retention behavior of the device. In vitro skin permeation study of LD was performed with modified Franz diffusion cell using rat skin and exhibited controlled release. The influence of storage time on release profile was investigated and demonstrated that after the initial burst, LD release profile of the device after 30 and 60days storage was identical to that of a device which was not stored. In vivo skin adhesion test and skin irritation assay in human subjects, water vapor permeability and environmental fitness test was performed to judge its application in biomedical field. All results displayed that the fabricated device is a potential candidate for TD LD administration to the systemic circulation. PMID:27516320

  5. Synthesis of nanocomposite 2-methyl-4-chlorophenoxyacetic acid with layered double hydroxide: physicochemical characterization and controlled release properties

    Energy Technology Data Exchange (ETDEWEB)

    Sarijo, Siti Halimah, E-mail: izaddinizaddin@yahoo.com; Ghazali, Sheikh Ahmad Izaddin Sheikh Mohd [Faculty of Applied Sciences, Universiti Teknologi MARA (Malaysia); Hussein, Mohd Zobir [Universiti Putra Malaysia, Department of Chemistry, Faculty of Science (Malaysia); Sidek, Norizzah Jaafar [Faculty of Applied Sciences, Universiti Teknologi MARA (Malaysia)

    2013-01-15

    A new organic-inorganic hybrid nanocomposite Zn-Al-MCPA-layered double hydroxide (ZAM) was prepared by intercalation of 2-methyl-4-chlorophenoxyacetic acid (MCPA) into Zn-Al-layered double hydroxide (ZAL) at various concentration of MCPA ranging from 0.1 to 0.7 M. The pH of the synthesis was kept constant at 7.5. Well-ordered hybrid nanocomposite was obtained with 0.4 M MCPA with an expansion of basal spacing from 8.9 Angstrom-Sign in the ZAL to 19.7 Angstrom-Sign in the resulting nanocomposite. The FTIR spectra of the nanocomposite show resemblance peaks of the MCPA and Zn-Al-layered double hydroxide indicating the inclusion of MCPA into the layered double hydroxide. The average particle size of ZAL and ZAM in this study was 115 and 128 nm, respectively. Percentage loading of MCPA was found to be 45.0 % (w/w), calculated based on the percentage of carbon in the sample. The release of MCPA into various aqueous solution was found to be dependent to the anion in the aqueous solution in the order of phosphate > sulfate > chloride with the percentage release of 80, 44, and 8%, respectively. This study shows that Zn-Al-layered double hydroxide can be used as a host carrier for herbicide, MCPA, with controlled release capability.

  6. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

    International Nuclear Information System (INIS)

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro

  7. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Shilei; Wang, Yazhou; Wang, Bochu, E-mail: wangbc2000@126.com; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-06-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro.

  8. Mineralization and drug release of hydroxyapatite/poly(l-lactic acid) nanocomposite scaffolds prepared by Pickering emulsion templating.

    Science.gov (United States)

    Hu, Yang; Zou, Shengwen; Chen, Weike; Tong, Zhen; Wang, Chaoyang

    2014-10-01

    Biodegradable and bioactive nanocomposite (NC) biomaterials with controlled microstructures and able to deliver special drugs have gained increasing attention in bone tissue engineering. In this study, the hydroxyapatite (HAp)/poly(l-lactic acid) (PLLA) NC scaffolds were facilely prepared using solvent evaporation from templating Pickering emulsions stabilized with PLLA-modified HAp (g-HAp) nanoparticles. Then, in vitro mineralization experiments were performed in a simulated body fluid (SBF) to evaluate the bioactivity of the NC scaffolds. Moreover, in vitro drug release of the NC scaffolds using anti-inflammatory drug (ibuprofen, IBU) as the model drug was also investigated. The results showed that the NC scaffolds possessed interconnected pore structures, which could be modulated by varying the g-HAp nanoparticle concentration. The NC scaffolds exhibited excellent bioactivity, since they induced the formation of calcium-sufficient, carbonated apatite nanoparticles on the scaffolds after mineralization in SBF for 3 days. The IBU loaded in the NC scaffolds showed a sustained release profile, and the release kinetic followed the Higuchi model with diffusion process. Thus, solvent evaporation based on Pickering emulsion droplets is a simple and effective method to prepare biodegradable and bioactive porous NC scaffolds for bone repair and replacement applications. PMID:25127362

  9. Engineering Saccharomyces cerevisiae to produce feruloyl esterase for the release of ferulic acid from switchgrass

    Science.gov (United States)

    The Aspergillus niger ferulic acid esterase gene (faeA) was cloned into Saccharomyces cerevisiae via a yeast expression vector, resulting in efficient expression and secretion of the enzyme in the medium. The recombinant enzyme was purified to homogeneity by anion-exchange and hydrophobic interactio...

  10. Effects of acid rain on competitive releases of Cd, Cu, and Zn from two natural soils and two contaminated soils in hunan, China

    OpenAIRE

    Liao, Bo-han; Guo, Zhao-hui; Zeng, Qingru; Probst, Anne; Probst, Jean-Luc

    2007-01-01

    Leaching experiments of rebuilt soil columns with two simulated acid rain solutions (pH 4.6– 3.8) were conducted for two natural soils and two artificial contaminated soils from Hunan, southcentralChina, to study effects of acid rain on competitive releases of soil Cd, Cu, and Zn. Distilled water was used in comparison. The results showed that the total releases were Zn>Cu>Cd for the natural soils and Cd>Zn≫Cu for the contaminated soils, which reflected sensitivity of these metals to acid rai...

  11. Diavik Waste Rock Project: Evolution of Mineral Weathering, Element Release, and Acid Generation and Neutralization during a Five-Year Humidity Cell Experiment

    OpenAIRE

    Jeff B. Langman; Mandy L. Moore; Carol J. Ptacek; Leslie Smith; David Sego; David W. Blowes

    2014-01-01

    A five-year, humidity-cell experiment was used to study the weathering evolution of a low-sulfide, granitic waste rock at 5 and 22 °C. Only the rock with the highest sulfide content (0.16 wt %) released sufficient acid to overcome a limited carbonate acid-neutralization capacity and produce a substantial decline in pH. Leached SO4 and Ca quickly increased then decreased during the first two years of weathering. Sulfide oxidation continued to release acid and SO4 after carbonate depletion, res...

  12. Poly(lactic acid) (PLA) based nanocomposites-a novel way of drug-releasing

    International Nuclear Information System (INIS)

    In this communication, poly(lactic acid) nanofibers have been fabricated by electrospinning and then poly(lactic acid) (PLA) based nanocomposites have been prepared by accumulating anticancer drug daunorubicin on PLA nanofibers combined with TiO2 nanoparticles. Our atomic force microscopy (AFM) and laser-scanning confocal microscope (LSCM) studies demonstrate that the respective drug molecules could be readily self-assembled on the surface of the blends of nano-TiO2 with PLA polymer nanocomposites, which could further efficiently facilitate the drug permeation and accumulation on the target leukemia K562 cells. Besides, the respective new nanocomposites have good biocompatibility, ease of surface chemistry modification and very high surface area, which may afford the possibility for their promising application in pharmacology and biomedical engineering areas. (communication)

  13. Release mechanism of omega-3 fatty acid in κ-carrageenan/polydextrose undergoing glass transition.

    Science.gov (United States)

    Paramita, Vilia Darma; Bannikova, Anna; Kasapis, Stefan

    2015-08-01

    A high-solid matrix of κ-carrageenan with polydextrose was developed to entrap α-linolenic acid, which is an omega-3 bioactive compound. Physicochemical analysis of this system utilised modulated DSC, dynamic oscillation in shear, ESEM, FTIR and WAX diffraction. The carbohydrate matrix was conditioned through an extensive temperature range to induce changes in molecular morphology and identify the network glass transition temperature. Thermally induced variation in phase morphology was employed to rationalise transportation patterns of the bioactive compound within the high-solid preparation. Thus, experimental observations using UV-vis spectroscopy modelled diffusion kinetics to document the mobility arresting effect of the vitrifying matrix on the micro-constituent. Within the glass transition region, results argue that free volume theory is the molecular process governing structural relaxation. Further, Less Fickian diffusion follows well the rate of molecular transport of α-linolenic acid as a function of time and temperature of observation in the condensed matrix. PMID:25933532

  14. The Loss of Weight and Release of Formaldehyde in Acid Treatment of Basofil Fiber

    Institute of Scientific and Technical Information of China (English)

    JIANG Hong

    2007-01-01

    The Basofil fiber is a new type of hightemperature fiber. Its Limiting Oxygen Index (LOI) value reaches 32. It does not melt, drop down or smolder when it contacts fire. The fiber is condensed from melamine and formaldehyde into a cross-linked with methylene-ether and methylene bridge bond. This thesis discusses the change of fiber structure and performance after the acid treatment.

  15. Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines

    OpenAIRE

    Pessione, Enrica; Cirrincione, Simona

    2016-01-01

    Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the ma...

  16. Reductive release of Fe(III) from bovine lactoferrin by ascorbic acid

    International Nuclear Information System (INIS)

    The kinetics of the reduction of Fe/sup 3+/ from bovine diferric Lactoferrin (Fe/sub 2/Lf) and monoferric C-terminal (Fe/sub C/-Lf) and N-terminal (Lf-Fe/sub N/) sites is investigated at ph 6.1 and 3.5 under pseudo first-order conditions using ascorbic acid (AA) as a biological reducing agent and 1, 10-Ortho phenanthroline (O-phen) as Fe/sup 2+/ chelator. Pseudo first-order rate constants as a function of ascorbic acid concentration are measured. Second order rate constants (k2) for Fe/sub 2/Lf, Lf-Fe/sub N/, Fe/sub C/-Lf at ph 6.1 and 27 deg. C are 0.1527 M/sup -1/.min/sup -1/, 0.0381 M/sup -1/.min-1, 0.1381 M/sup -1/.min/sup -1/, respectively. While, at ph 3.5 and 27 deg. C these values are 0.1915 M/sup -1/.min-1, 0.1116 M/sup -1/.min/sup -1/, 0.4434 M/sup -/.min/sup -1/, respectively. A linear dependence of k/sub obs/ on ascorbic acid concentration is suggestive of simple pseudo first-order pathway for reduction of iron under the conditions applied for all the three forms of protein. Moreover, the results show that the C-terminal site is more labile toward reduction by ascorbic acid than the N-terminal site. (author)

  17. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

    OpenAIRE

    Hussein MZ; Al Ali SH; Zainal Z; Hakim MN

    2011-01-01

    Mohd Zobir Hussein1,2, Samer Hasan Al Ali2, Zulkarnain Zainal2, Muhammad Nazrul Hakim31Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology (ITMA), 2Department of Chemistry, Faculty of Science, 3Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: An ellagic acid (EA)–zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc o...

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

    Science.gov (United States)

    Gatto, Francesco; Schulze, Almut; Nielsen, Jens

    2016-07-19

    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. PMID:27396332

  19. 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.

  20. Arachidonate 15-lipoxygenase type B knockdown leads to reduced lipid accumulation and inflammation in atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Lisa U Magnusson

    Full Text Available Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B is more highly expressed in human atherosclerotic lesions than in healthy arteries. This enzyme oxidizes fatty acids to substances that promote local inflammation and is expressed in lipid-loaded macrophages (foam cells present in the atherosclerotic lesions. Here, we investigated the role of ALOX15B in foam cell formation in human primary macrophages and found that silencing of human ALOX15B decreased cellular lipid accumulation as well as proinflammatory cytokine secretion from macrophages. To investigate the role of ALOX15B in promoting the development of atherosclerosis in vivo, we used lentiviral shRNA silencing and bone marrow transplantation to knockdown mouse Alox15b gene expression in LDL-receptor-deficient (Ldlr(-/- mice. Knockdown of mouse Alox15b in vivo decreased plaque lipid content and markers of inflammation. In summary, we have shown that ALOX15B influences progression of atherosclerosis, indicating that this enzyme has an active proatherogenic role.

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

    Science.gov (United States)

    Šerý, Omar; Hlinecká, Lýdia; Povová, Jana; Bonczek, Ondřej; Zeman, Tomáš; Janout, Vladimír; Ambroz, Petr; Khan, Naim A; Balcar, Vladimir J

    2016-03-15

    Dementias of old age, in particular Alzheimer's disease (AD), pose a growing threat to the longevity and quality of life of individuals as well as whole societies world-wide. The risk factors are both genetic and environmental (life-style) and there is an overlap with similar factors predisposing to cardiovascular diseases (CVD). Using a case-control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD. ALOX5 gene encodes a 5'-lipoxygenase (5'-LO) activating protein (FLAP), a crucial component of the arachidonic acid/leukotriene inflammatory cascade. A-allele of rs4769874 polymorphism increases the risk of AD 1.41-fold (p<0.0001), while AA genotype does so 1.79-fold (p<0.0001). In addition, GG genotype of rs4769874 polymorphism is associated with a modest increase in body mass index (BMI). We discuss potential biochemical mechanisms linking the SNP to AD and suggest possible preventive pharmacotherapies some of which are based on commonly available natural products. Finally, we set the newly identified AD risk factors into a broader context of similar CVD risk factors to generate a more comprehensive picture of interacting genetics and life-style habits potentially leading to the deteriorating mental health in the old age. PMID:26944113

  2. The application of layered double hydroxide clay (LDH)-poly(lactide-co-glycolic acid) (PLGA) film composites for the controlled release of antibiotics

    DEFF Research Database (Denmark)

    Chakraborti, Michelle; Jackson, John K.; Plackett, David;

    2012-01-01

    complexes in poly(lactic-co-glycolic acid) films resulted in a reduced burst phase of release and a slow continuous release for many weeks with effective antimicrobial amounts of VAN and SF released at later time points. Layered double hydroxide clays may be useful for controlled release applications at...... quantitation of the unbound fraction by UV/Vis absorbance or HPLC analysis. Drug release from layered double hydroxide clay/drug complexes dispersed in polymeric films was measured by incubation in phosphate-buffered saline (pH 7.4) at 37 °C using absorbance or HPLC analysis. Antimicrobial activity of drug...... sites requiring long-term antibiotic exposure as they maintain the drug in a non-degraded state and release effective amounts of drug over long time periods. LDH clay/drug complexes are amenable to homogenous dispersion in polymeric films where implant coating may be optimal or required....

  3. Behaviour of U-Isotopes in an Estuary Affected by Acid Mine Drainage and Industrial Releases

    International Nuclear Information System (INIS)

    Tinto and Odiel rivers (SW of Spain) is an ecosystem of great interest that is seriously affected by acid mine drainage (AMD) from long-term mining activities (pH < 3). Additionally, a large industrial complex is located in the surroundings of this estuary and Huelva town, which includes two phosphate rock processing plants that produce about 3 millions of tons per year of a byproduct called phosphogypsum (PG) containing high U-series radionuclides concentrations. For these reasons, the estuary of Huelva is one of the most heavy metals and radionuclides polluted estuarine systems in Europe with extremely low pH.

  4. Preparation of HIFU-triggered tumor-targeted hyaluronic acid micelles for controlled drug release and enhanced cellular uptake.

    Science.gov (United States)

    Zheng, Shaohui; Jin, Zhen; Han, Jiwon; Cho, Sunghoon; Nguyen, Van Du; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2016-07-01

    In this study, a novel type of high intensity focused ultrasound (HIFU)-triggered active tumor-targeting polymeric micelle was prepared and investigated for controlled drug release and enhanced cellular uptake. Amphiphilic hyaluronic acid (HA) conjugates were synthesized to form docetaxel loaded micelles in aqueous conditions with high encapsulation efficiencies of over 80%. The micelle sizes were limited to less than 150nm, and they varied slightly according to the encapsulated drug amount. Modifying the micellar surface modification with polyethylene glycol diamine successfully inhibited premature drug leakage at a certain level, and it can be expected to prolong the circulation time of the particles in blood. In addition, high-intensity focused ultrasound was introduced to control the release of docetaxel from micelles, to which the release behavior of a drug can be tuned. The in-vitro cell cytotoxicity of docetaxel-loaded micelles was verified against CT-26 and MDA-MB-231 cells. The IC50 values of drug-loaded micelles to CT-26 and MDA-MB-231 cells were 1230.2 and 870.9ng/mL, respectively. However, when exposed to HIFU, the values decreased significantly, to 181.9 and 114.3ng/mL, suggesting that HIFU can enhance cell cytotoxicity by triggering the release of a drug from the micelles. Furthermore, cellular uptake tests were conducted via the quantitative analysis of intracellular drug concentration within CT-26 (CD44 negative), MDA-MB-231 (CD44 positive), and MDA-MB-231 (CD44 blocked), and then imaged with coumarin-6 loaded micelles. The results verified that intracellular drug delivery can be enhanced efficiently via the CD44 receptor-mediated endocytosis of HA micelles. Moreover, HIFU enhanced the cellular uptake behavior by altering the permeability of the cell membrane. It was also able to aid with the extravasation of micelles into the interior of tumors, which will be explained in further research. Therefore, the present study demonstrates that the micelles

  5. Photo-crosslinked networks prepared from fumaric acid monoethyl ester-functionalized poly(D,L-lactic acid) oligomers and N-vinyl-2-pyrrolidone for the controlled and sustained release of proteins

    NARCIS (Netherlands)

    Jansen, Janine; Tibbe, Martijn P.; Mihov, George; Feijen, Jan; Grijpma, Dirk W.

    2012-01-01

    Photo-crosslinked networks were prepared from fumaric acid monoethyl ester-functionalized poly (D,L-lactic acid) oligomers and N-vinyl-2-pyrrolidone. Two model proteins, lysozyme and albumin, were incorporated into the network films as solid particles and their release behavior was studied. By varyi

  6. Two distinct modes of hypoosmotic medium-induced release of excitatory amino acids and taurine in the rat brain in vivo.

    Directory of Open Access Journals (Sweden)

    Renée E Haskew-Layton

    Full Text Available A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl] medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i kinetic properties, (ii sensitivity to isoosmotic changes in [NaCl], and (iii sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo.

  7. Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives.

    Science.gov (United States)

    Xie, Tian; Taylor, Lynne S

    2016-03-01

    Amorphous solid dispersions (ASDs) have been extensively exploited as a strategy for improving the dissolution performance of poorly water-soluble drugs. However, factors underpinning the observed dissolution profiles are not clearly understood, and the choice of polymeric carriers is largely empirical. In the current study, the dissolution performance of a high drug loading ASD containing the poorly water-soluble, anti-inflammatory agent, celecoxib, was optimized by using binary polymers combinations. Polyacrylic acid (PAA), a highly water-soluble polymer, was used to substantially increase the dissolution rate of the drug, while hydroxypropyl methyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS) were added to stabilize the solid amorphous matrix against crystallization upon hydration, as well as to maintain supersaturation. Quantitative measurements of the impact of the polymers on the solution nucleation and growth rates of celecoxib revealed that, while the cellulose derivatives are effective nucleation inhibitors, it is more difficult to completely prevent crystal growth in solutions containing seed crystals, in particular at high supersaturations. Therefore, it is critical to prevent the formation of crystals in the dissolving matrix during dissolution. By using certain ratios of HPMC and PAA, both rapid release as well as crystallization inhibition could be achieved, even at high drug loadings. Utilizing combinations of polymers may therefore be useful to tailor release profiles while providing optimized crystallization inhibition. PMID:26791934

  8. Release of UV-absorbing substances from maize coleoptiles during auxin-, fusicoccin- and acid-mediated elongation growth

    International Nuclear Information System (INIS)

    Isolated cell walls from maize coleoptiles prepared under conditions that preserve the ability for enzymatic hemicellulose autolysis release UV-absorbing substances into the incubation medium in a time-dependent reaction with an optimal rate at pH 6–7. The reaction can be inhibited by low temperature and protein-denaturing treatments, indicating an enzymatic process. Spectroscopic and chromatographic analyses showed that the liberated substances represent a complex mixture of free and bound (alkali-hydrolyzable) phenolic compounds with similar absorption spectra restricted to the range below 300 nm and thus excluding hydroxycinnamic acids from cell-wall esters. A spectroscopically and chromatographically similar mixture of soluble UV-absorbing substances is released if living (abraded) maize coleoptiles or coleoptile segments are incubated in water or buffer, suggesting that insoluble phenolic materials in the cell wall are metabolized also in vivo. This reaction can be promoted by anaerobic conditions and application of fusicoccin whereas auxin had a slightly inhibitory effect. No clear relationship to elongation growth could be demonstrated. We conclude from these results that polymeric phenolic constituents of the cell wall are subject to enzymatic degradation in muro similar to polysaccharide autolysis and that this process is under metabolic control

  9. 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.

  10. Microwave-assisted Polymerization of ε-Caprolactone with Maleic Acid as Initiator and Drug Release Behavior of Ibuprofen-Poly(ε-caprolaetone) System

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Poly(ε-caprolactone) (PCL) with weight-average molar mass over 10000 g/mol was synthesized by microwave-assisted ring-opening polymerization of ε-caprolactonc (ε-CL) with malcic acid (MA) as initiator (2.45 GHz, 360 W, 85 min). Ibuprofen-PCL controlled release system was prepared directly by the ROP of ε-CL in its mixture with ibuprofen. The release of ibuprofen from the system was sustained and steady.

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

    Directory of Open Access Journals (Sweden)

    Nurhasni H

    2015-04-01

    Full Text Available Hasan Nurhasni,1 Jiafu Cao,1 Moonjeong Choi,1 Il Kim,2 Bok Luel Lee,1 Yunjin Jung,1 Jin-Wook Yoo11College of Pharmacy, Pusan National University, Busan, South Korea; 2Department of Polymer Science and Engineering, Pusan National University, Busan, South KoreaAbstract: Nitric oxide (NO-releasing nanoparticles (NPs have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid-polyethylenimine (PEI NPs (NO/PPNPs composed of poly(lactic-co-glycolic acid and PEI/diazeniumdiolate (PEI/NONOate for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections.Keywords: nitric oxide-releasing nanoparticles, PLGA, PEI, antimicrobial, wound healing

  12. PEG-detachable and acid-labile cross-linked micelles based on orthoester linked graft copolymer for paclitaxel release

    Science.gov (United States)

    Yuan, Zhefan; Huang, Jingyi; Liu, Jing; Cheng, Sixue; Zhuo, Renxi; Li, Feng

    2011-08-01

    Polyethylene glycol detachable graft copolymer, mPEG-g-p(NAS-co-BMA), was synthesized by grafting 2-(ω-methoxy)PEGyl-1,3-dioxan-5-ylamine onto poly(N-(acryloyloxy)succinimide-co-butyl methacrylate). Pseudo in situ cross-linking of the mPEG-g-p(NAS-co-BMA) was performed in dimethylformamide phosphate buffer (v/v = 1/1) by an acid-labile diamine cross-linker bearing two symmetrical cyclic orthoesters. The cross-linked (CL) micelles with different contents of mPEG segments represented different morphologies. The CL micelles containing approximately one mPEG segment exhibited 'echini' morphology whereas the CL micelle with approximately three mPEG segments formed nanowires. The hydrolysis rate of the CL micelles is highly pH-dependent and much more rapid at mild acid than physiological conditions. Hydrolyzates of the CL micelles formed vesicles because new amphiphilic copolymers were formed. Paclitaxel (PTX) was successfully loaded into the CL micelles and a controlled and pH-dependent release behavior was observed. No obvious cytotoxicity was found for the CL micelles at concentration as high as 800 mg l - 1.

  13. Dissolving behavior and calcium release from fibrous wollastonite in acetic acid solution

    International Nuclear Information System (INIS)

    The degradability of fibrous wollastonite (CaSiO3) in an aqueous solution of acetic acid and leaching of Ca2+ ions were investigated in the temperature range from 22 to 50 oC. The Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES) was used for the assessment of calcium and other selected cations in the leaching medium. The amount of calcium in the solvent can be significantly enhanced through leaching at higher temperature. Fibrous silica particles are the main by-product of the leaching process. The properties of by-product were examined by thermal analysis (simultaneous TG-DTA-EGA), infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The formation of silica layer on the surface of fibrous wollastonite particles is an important factor in the leaching process. Particles were covered by the silica layer and wollastonite core size was continually decreasing during leaching. The shape of resulting silica particles shows no significant changes during this process. Specific surface of the formed fibrous silica particles strongly depends on the leaching temperature.

  14. Whey protein/polysaccharide-stabilized oil powders for topical application-release and transdermal delivery of salicylic acid from oil powders compared to redispersed powders.

    Science.gov (United States)

    Kotzé, Magdalena; Otto, Anja; Jordaan, Anine; du Plessis, Jeanetta

    2015-08-01

    Oil-in-water (o/w) emulsions are commonly converted into solid-like powders in order to improve their physical and chemical stabilities. The aim of this study was to investigate whether whey protein/polysaccharide-stabilized o/w emulsions could be converted into stable oil powders by means of freeze-drying. Moreover, during this study, the effects of pH and polymer type on release and trans(dermal) delivery of salicylic acid, a model drug, from these oil powders were investigated and compared to those of the respective template emulsions and redispersed oil powders. Physical characterization of the various formulations was performed, such as droplet size analysis and oil leakage, and relationships drawn with regards to release and trans(dermal) delivery. The experimental outcomes revealed that the oil powders could be redispersed in water without changing the release characteristics of salicylic acid. pH and polymer type affected the release of salicylic acid from the oil powders, template emulsions, and redispersed powders similarly. Contrary, the transdermal delivery from the oil powders and from their respective redispersed oil powders was differently affected by pH and polymer type. It was hypothesized that the release had been influenced by the electrostatic interactions between salicylic acid and emulsifiers, whereas the transdermal performance could have been determined by the particle or aggregate sizes of the formulations. PMID:25573437

  15. Differential Release of Lipoteichoic and Teichoic Acids from Streptococcus pneumoniae as a Result of Exposure to β-Lactam Antibiotics, Rifamycins, Trovafloxacin, and Quinupristin-Dalfopristin

    OpenAIRE

    Stuertz, K; Schmidt, H.; Eiffert, H.; Schwartz, P.; Mäder, M.; Nau, R.

    1998-01-01

    The release of lipoteichoic acid (LTA) and teichoic acid (TA) from a Streptococcus pneumoniae type 3 strain during exposure to ceftriaxone, meropenem, rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin in tryptic soy broth was monitored by a newly developed enzyme-linked immunosorbent assay. At a concentration of 10 μg/ml, a rapid and intense release of LTA and TA occurred during exposure to ceftriaxone (3,248 ± 1,688 ng/ml at 3 h and 3,827 ± 2,133 ng/ml at 12 h) and meropenem ...

  16. Preparation of Surfactant-free Core-Shell Poly(lactic acid) / Calcium Phosphate Hybrid Particles and Their Drug Release Characteristics

    International Nuclear Information System (INIS)

    We propose surfactant-free core-shell poly(lactic acid) (PLA) / calcium phosphate (CaP) hybrid particles as drug delivery carriers. These particles were prepared by biomineralization process using ultrasonic irradiation, and their drug release profiles were investigated. Drug release rate was earlier when particles were prepared by PLA with a low molecular weight, and/or by Ca(CH3COO)2 and (NH4)2HPO4. Also, these were shown good protein adsorption. This work indicates that these particles have sustained-release ability without initial burst and can do targeting capability by biomolecule conjugation.

  17. Catecholamine release and potentiation of thromboxane A2 production by nicotine in the greyhound.

    OpenAIRE

    Dusting, G J; D.M. Li

    1986-01-01

    Thromboxane A2 was generated by infusing arachidonic acid (2.5 micrograms ml-1) into an extra-corporeal circuit of blood withdrawn from anaesthetized dogs, and assayed on a blood-bathed bioassay cascade of porcine and bovine coronary artery strips, chick rectum and rat stomach strip. All tissues except chick rectum were treated with phentolamine and propranolol to abolish direct effects of catecholamines. The arachidonate-induced contractions of artery strips were abolished by a thromboxane s...

  18. The gastric acid secretagogue gastrin-releasing peptide and the inhibitor oxyntomodulin do not exert their effect directly on the parietal cell in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Holst, J J

    1988-01-01

    Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production in...... vitro by measuring [14C]-aminopyrine accumulation, a reliable index of H+ generation, in isolated rat parietal cells. However, neither gastrin-releasing peptide nor oxyntomodulin influenced basal acid secretion or histamine-stimulated gastric acid secretion. Electron-microscopic studies of unstimulated...... and histamine-stimulated parietal cells confirmed that the cells retained the normal morphology of intracellular organelles and that the cells responded to physiological stimulation by marked expansion of the intracellular canaliculi....

  19. Differences in Clinical Manifestation of Streptococcus pneumoniae Infection Are Not Correlated with In Vitro Production and Release of the Virulence Factors Pneumolysin and Lipoteichoic and Teichoic Acids

    OpenAIRE

    Spreer, Annette; Lis, Astrid; Gerber, Joachim; Reinert, Ralf René; Eiffert, Helmut; Nau, Roland

    2004-01-01

    Production and release of the pneumococcal virulence factors pneumolysin and lipoteichoic and teichoic acid in 75 clinical isolates were investigated. No difference was found between strains causing systemic infection or localized respiratory infection and isolates from asymptomatic carriers. This suggests that the presence of pneumolysin and lipoteichoic and teichoic acid is a necessary but not a sufficient condition for pneumococcal infection and development of invasive disease.

  20. OMEGA-3 fatty acids contribute to plaque stability differentially affecting the release of matrix metalloproteinases and tissue inhibitors of metalloproteinases by human monocytes/macrophages in culture

    OpenAIRE

    Massaro, Marika; Scoditti, Egeria; Carluccio, Maria Annunziata; Storelli, Carlo; Distante, Alessandro; Martines, Giuseppe

    2008-01-01

    Objectives. High intakes of omega-3 fatty acids has been associated with protection from plaque rupture. The secretion of metalloproteinases (MMPs) by macrophages is believed to play a key role in matrix degradation underlying plaque instability. Conversely, tissue inhibitors of metalloproteinases (TIMPs) would contribute to plaque stability. We therefore studied the effects of omega-3 fatty acids on the release and activity of MMPs and TIMPs in cultured human monocytoid cells. Methods. Human...

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

    Science.gov (United States)

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

    2015-09-18

    The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs. PMID:26093053

  2. Phenylboronic Acid Appended Pyrene-Based Low-Molecular-Weight Injectable Hydrogel: Glucose-Stimulated Insulin Release.

    Science.gov (United States)

    Mandal, Deep; Mandal, Subhra Kanti; Ghosh, Moumita; Das, Prasanta Kumar

    2015-08-17

    A pyrene-containing phenylboronic acid (PBA) functionalized low-molecular-weight hydrogelator was synthesized with the aim to develop glucose-sensitive insulin release. The gelator showed the solvent imbibing ability in aqueous buffer solutions of pH values, ranging from 8-12, whereas the sodium salt of the gelator formed a hydrogel at physiological pH 7.4 with a minimum gelation concentration (MGC) of 5 mg mL(-1) . The aggregation behavior of this thermoreversible hydrogel was studied by using microscopic and spectroscopic techniques, including transmission electron microscopy, FTIR, UV/Vis, luminescence, and CD spectroscopy. These investigations revealed that hydrogen bonding, π-π stacking, and van der Waals interactions are the key factors for the self-assembled gelation. The diol-sensitive PBA part and the pyrene unit in the gelator were judiciously used in fluorimetric sensing of minute amounts of glucose at physiological pH. The morphological change of the gel due to addition of glucose was investigated by scanning electron microscopy, which denoted the glucose-responsive swelling of the hydrogel. A rheological study indicated the loss of the rigidity of the native gel in the presence of glucose. Hence, the glucose-induced swelling of the hydrogel was exploited in the controlled release of insulin from the hydrogel. The insulin-loaded hydrogel showed thixotropic self-recovery property, which hoisted it as an injectable soft composite. Encouragingly, the gelator was found to be compatible with HeLa cells. PMID:26184777

  3. Effect of brain-derived neurotropic factor released from hypoxic astrocytes on gamma-aminobutyric acid type A receptor function in normal hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongliang Liu; Tijun Dai

    2011-01-01

    Astrocytes can release increased levels of brain-derived neurotrophic factor during cerebral ischemia, but it is unclear whether brain-derived neurotrophic factor affects γ-aminobutyric acid type A receptor function in normal neurons. Results from this study demonstrated that γ-aminobutyric acid at 100 μmol/L concentration raised the intracellular calcium level in neurons treated with medium from cultured hypoxic astrocytes, and the rise in calcium level could be inhibited by γ-aminobutyric acid type A receptor antagonist bicuculline or brain-derived neurotrophic factor receptor antagonist k252a. Γ-aminobutyric acid type A-gated current induced by 100 μmol/L γ-aminobutyric acid was in an inward direction in physiological conditions, but shifted to the outward direction in neurons when treated with the medium from cultured hypoxic astrocytes, and this effect could be inhibited by k252a. The reverse potential was shifted leftward to -93 Mv, which could be inhibited by k252a and Na+-K+-Cl- cotransporter inhibitor bumetanide. Brain-derived neurotrophic factor was released from hypoxic astrocytes at a high level. It shifted the reverse potential of γ-aminobutyric acid type A-gated currents leftward in normal neurons by enhancing the function of Na+-K+-Cl- cotransporter, and caused γ-aminobutyric acid to exert an excitatory effect by activating γ-aminobutyric acid type A receptor.

  4. Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid/Poly(vinyl alcohol IPN Hydrogel and Its Drug Controlled Release

    Directory of Open Access Journals (Sweden)

    Jingqiong Lu

    2015-01-01

    Full Text Available Modified poly(aspartic acid/poly(vinyl alcohol interpenetrating polymer network (KPAsp/PVA IPN hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid grafting 3-aminopropyltriethoxysilane (KH-550 and poly(vinyl alcohol (PVA as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR and scanning electron microscopy (SEM. The thermal stability was analyzed by thermogravimetric analysis (TGA. The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN, and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid and 62.5 wt% at pH = 7.4 (simulated intestinal fluid, respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery.

  5. Diavik Waste Rock Project: Evolution of Mineral Weathering, Element Release, and Acid Generation and Neutralization during a Five-Year Humidity Cell Experiment

    Directory of Open Access Journals (Sweden)

    Jeff B. Langman

    2014-04-01

    Full Text Available A five-year, humidity-cell experiment was used to study the weathering evolution of a low-sulfide, granitic waste rock at 5 and 22 °C. Only the rock with the highest sulfide content (0.16 wt % released sufficient acid to overcome a limited carbonate acid-neutralization capacity and produce a substantial decline in pH. Leached SO4 and Ca quickly increased then decreased during the first two years of weathering. Sulfide oxidation continued to release acid and SO4 after carbonate depletion, resulting in an increase in acid-soluble elements, including Cu and Zn. With the dissolution of Al-bearing minerals, the pH stabilized above 4, and sulfide oxidation continued to decline until the end of the experiment. The variation in activation energy of sulfide oxidation correlates with changes in sulfide availability, where the lowest activation energies occurred during the largest releases of SO4. A decrease in sulfide availability was attributed to consumption of sulfide and weathered rims on sulfide grains that reduced the oxidation rate. Varying element release rates due to changing carbonate and sulfide availability provide identifiable geochemical conditions that can be viewed as neutralization sequences and may be extrapolated to the field site for examining the evolution of mineral weathering of the waste rock.

  6. Effect of low severity dilute-acid pretreatment of barley straw and decreased enzyme loading hydrolysis on the production of fermentable substrates and the release of inhibitory compounds

    NARCIS (Netherlands)

    Panagiotopoulos, I.A.; Lignos, G.D.; Bakker, R.R.C.; Koukios, E.G.

    2012-01-01

    The objective of this work was to investigate the feasibility of combining low severity dilute-acid pretreatment of barley straw and decreased enzyme loading hydrolysis for the high production of fermentable substrates and the low release of inhibitory compounds. For most of the pretreatments at 160

  7. Alpha-linolenic acid regulates the growth of breast and cervical cancer cell lines through regulation of NO release and induction of lipid peroxidation

    Directory of Open Access Journals (Sweden)

    Ruchika Kaul-Ghanekar

    2013-02-01

    Full Text Available In the present work, we have analyzed the effect of the essential fatty acid, alpha linolenic acid (ALA on nitric oxide release as well as induction of lipid peroxidation in breast (MCF-7 and MDA-MB-231 and cervical (SiHa and HeLa cancer cell lines. ALA-treated cells showed a dose-dependent decrease in cell viability in both breast and cervical cancer cell lines without affecting the viability of non-cancerous transformed HEK 293 cells. Both types of cancer cells treated with ALA demonstrated a significant reduction in nitric oxide (NO release with a simultaneous increase in lipid peroxidation (LPO. This was followed by a decrease in the mitochondrial membrane potential as well as activation of caspase 3 leading to apoptosis. Thus, ALA regulated the growth of cancer cell lines through induction of lipid peroxidation and modulation of nitric oxide release resulting in apoptosis.

  8. Recognition of acidic phospholipase A2 activity in plasma membranes of resident peritoneal macrophages

    International Nuclear Information System (INIS)

    Phospholipase (PLase) activities in the plasma membrane of guinea pig peritoneal macrophages were studied, as these enzymes having such activity may be candidates for the release of arachidonic acid (AA) from phosphatidylcholine (PC). An AA release system operating at acidic pH was identified in the macrophage plasma membrane and characterized. This membrane-bound acidic PLase A2 had an optimum pH at 4.5, and enzyme activation was observed in Ca++-free medium; but the maximum activity was found at 0.5 mM Ca++ concentration. The Km value for PC of acidic PLase A2 was 4.2 μM, and a Michaelis-Menten relationship was evident. Calcium might act as a cofactor at some intermediate step during the activation of acidic PLase A2 in light of the uncompetitive manner of Ca++ action. Furthermore, the release of [3H]-AA from preradiolabelled macrophage plasma membranes occurred with the addition of Ca++ at pH 4.5. These data suggest that the acid PLase A2 is a component of the plasma membrane and is not due to lysosomal contamination since membrane-bound acidic PLase A2 properties are opposite to those found for lysosomal PLase A2

  9. NUTRIENT RELEASE FROM CONTROLLLED-RELEASE FERTILIZERS IN ACID SUBSTRATE IN A GREENHOUSE ENVIRONMENT: II.LEACHATE CALCIUM, MAGNESIUM, IRON MANGANESE, ZINC, COPPER, AND MOLYBDENUM CONCENTRATIONS

    Science.gov (United States)

    Leachate from containerized substrate containing one of four different controlled-release fertilizers (Osmocote, Nutricote, Polyon, or Multicote) were monitored for concentrations of Ca, Mg, Fe, Mn, Zn, Cu and Mo during a 47-week period. Environmental and cultural practices simulated an unheated gr...

  10. Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin.

    Science.gov (United States)

    Kong, Bong Ju; Kim, Ayoung; Park, Soo Nam

    2016-08-20

    In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA-HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. PMID:27178954

  11. Peptide Synthesis through Cell-Free Expression of Fusion Proteins Incorporating Modified Amino Acids as Latent Cleavage Sites for Peptide Release.

    Science.gov (United States)

    Liutkus, Mantas; Fraser, Samuel A; Caron, Karine; Stigers, Dannon J; Easton, Christopher J

    2016-05-17

    Chlorinated analogues of Leu and Ile are incorporated during cell-free expression of peptides fused to protein, by exploiting the promiscuity of the natural biosynthetic machinery. They then act as sites for clean and efficient release of the peptides simply by brief heat treatment. Dehydro analogues of Leu and Ile are similarly incorporated as latent sites for peptide release through treatment with iodine under cold conditions. These protocols complement enzyme-catalyzed methods and have been used to prepare calcitonin, gastrin-releasing peptide, cholecystokinin-7, and prolactin-releasing peptide prohormones, as well as analogues substituted with unusual amino acids, thus illustrating their practical utility as alternatives to more traditional chemical peptide synthesis. PMID:26918308

  12. Effects of the gamma-aminobutyrate transaminase inhibitors gabaculine and gamma-vinyl GABA on gamma-aminobutyric acid release from slices of rat cerebral cortex

    International Nuclear Information System (INIS)

    The release of [3H]gamma-aminobutyric acid (GABA) from pre-loaded slices of rat cerebral cortex was investigated in the presence and absence of the GABA-transaminase inhibitors gabaculine and gamma-vinyl GABA. In the experiments carried out without an inhibitor, an ion-exchange column chromatographic technique was used to separate [3H]GABA from tritiated metabolites released with it into the superfusate. The presence of gabaculine (5 microM) substantially reduced the Ca2+-dependence of the release of [3H]GABA evoked by a 4 min 30 mM K+ pulse, whereas this was not appreciably reduced by the presence of gamma-vinyl GABA (2 mM or 10 mM). Nevertheless, the characteristics of [3H]GABA release were not identical in the presence and absence of either inhibitor

  13. Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins

    Energy Technology Data Exchange (ETDEWEB)

    Hamberg, M.; Svensson, J.; Samuelsson, B.

    1974-10-01

    Methods were developed for quantitative determination of the three major metabolites of arachidonic acid in human platelets, i.e., 12L-hydroxy-5,8,10,14-cicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD). Aggregation of washed platelets by thrombin was accompanied by release of 1163 to 2175 ng/ml of HETE, 1129 to 2430 ng/ml of HHT, and 998 to 2299 ng/ml of PHD. The amount of PGG/sub 2/ (prostaglandin G/sub 2/) produced as calculated from the sum of the amounts of its metabolites (HHT and PHD) was 2477 to 5480 ng/ml. In contrast, the amounts of PGF/sub 2/ (prostaglandin E/sub 2/) and PGF/sub 2..cap alpha../ (prostaglandin F/sub 2..cap alpha../) released were approximately two orders of magnitude lower. In this system, the prostaglandins thus exert their biological action through the endoperoxides, which are almost exclusively metabolized to nonprostanoate structures and only to a small extent to the classical prostaglandins. Platelets from subjects given aspirin produced less than 5% of the above mentioned amounts of HHT and PHD, whereas the production of HETE was stimulated about 3-fold. This provides additional evidence for our earlier proposal that the anti-aggregating effect of aspirin is through inhibition of PGG/sub 2/ formation.

  14. Effect of malic acid on aluminum and silicon release from kaolinite%苹果酸对高岭石中铝和硅释放的影响

    Institute of Scientific and Technical Information of China (English)

    胡华锋; 王慧杰; 王兴祥; 介晓磊; 李清曼

    2013-01-01

    Experiment was conducted to investigate the long-time dissolution effects of water-eluviated and acid-eluviated kaolinite with batch method in malic acid solution. The results showed that malic acid significantly enhanced Al and Si release from kaolinite, and release of Al and Si from kaolinite increased with the increase of concentration of malic acid. Acid-eluviated kaolinite was more easily dissolved than that of water-eluviated kaolinite. When the concentration of malic acid was 20 mmol·L-1, after reaction for 936 hours, the release amount of Al and Si from water-eluviated kaolinite was 0.51 mmol·L-1 and 0.57 mmol·L-1, which were 86.44% and 83.82% of the release amount of Al and Si from acid-eluviated kaolinite. The preferential Si-release of kaolinite was observed initially, but at reaction anaphase, when the concentration of malic acid were less than 20 mmol/L, Al and Si showed stoichiometric release. Dissolution rate of kaolinite increased with the increase of concentration of malic acids, and dissolution rate of acid-eluviated kaolinite was higher than that of water-eluviated kaolinite; the dissolution rate didn't show the character of saturation, and the dissolution rate indiated the increasing character of linearity; malic acid significantly enhanced Al and Si release from kaolinite, and the acid-eluviated kaolinite was more easily dissolved than water-eluviated kaolinite in the malic acids reactive solution.%采用间歇法(batch method)模拟研究水洗和酸洗高岭石在苹果酸溶液中的长期溶解效应及其相对溶解能力.结果表明,水洗和酸水高岭石反应液中Al、Si离子浓度均随苹果酸浓度的增加而升高,且酸洗高岭石中Al、Si离子更易释放;当苹果酸浓度为20 mmol·L-1时,反应936h后,水洗高岭石Al、Si的释放量为0.51 mmol·L-1和0.57 mmol·L-1,分别是酸洗高岭石Al、Si释放量的86.44%和83.82%.高岭石反应前期表现为Si的优先释放,而在反

  15. Characterisation of adipocyte-derived extracellular vesicles released pre- and post-adipogenesis

    Directory of Open Access Journals (Sweden)

    Katherine D. Connolly

    2015-11-01

    Full Text Available Extracellular vesicles (EVs are submicron vesicles released from many cell types, including adipocytes. EVs are implicated in the pathogenesis of obesity-driven cardiovascular disease, although the characteristics of adipocyte-derived EVs are not well described. We sought to define the characteristics of adipocyte-derived EVs before and after adipogenesis, hypothesising that adipogenesis would affect EV structure, molecular composition and function. Using 3T3-L1 cells, EVs were harvested at day 0 and day 15 of differentiation. EV and cell preparations were visualised by electron microscopy and EVs quantified by nanoparticle tracking analysis (NTA. EVs were then assessed for annexin V positivity using flow cytometry; lipid and phospholipid composition using 2D thin layer chromatography and gas chromatography; and vesicular protein content by an immuno-phenotyping assay. Pre-adipogenic cells are connected via a network of protrusions and EVs at both time points display classic EV morphology. EV concentration is elevated prior to adipogenesis, particularly in exosomes and small microvesicles. Parent cells contain higher proportions of phosphatidylserine (PS and show higher annexin V binding. Both cells and EVs contain an increased proportion of arachidonic acid at day 0. PREF-1 was increased at day 0 whilst adiponectin was higher at day 15 indicating EV protein content reflects the stage of adipogenesis of the cell. Our data suggest that EV production is higher in cells before adipogenesis, particularly in vesicles <300 nm. Cells at this time point possess a greater proportion of PS (required for EV generation whilst corresponding EVs are enriched in signalling fatty acids, such as arachidonic acid, and markers of adipogenesis, such as PREF-1 and PPARγ.

  16. Polyunsaturated fatty acids and inflammation

    Directory of Open Access Journals (Sweden)

    Calder Philip C.

    2004-01-01

    Full Text Available The n-6 polyunsaturated fatty acid arachidonic acid gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites and through these regulates the activities of inflammatory cells, the production of cytokines and the various balances within the immune system. Fish oil and oily fish are good sources of long chain n-3 polyunsaturated fatty acids. Consumption of these fatty acids decreases the amount of arachidonic acid in cell membranes and so available for eicosanoid production. Thus, n-3 polyunsaturated fatty acids act as arachidonic acid antagonists. Components of both natural and acquired immunity, including the production of key inflammatory cytokines, can be affected by n-3 polyunsaturated fatty acids. Although some of the effects of n-3 fatty acids may be brought about by modulation of the amount and types of eicosanoids made, it is possible that these fatty acids might elicit some of their effects by eicosanoid-independent mechanisms. Such n-3 fatty acid-induced effects may be of use as a therapy for acute and chronic inflammation, and for disorders that involve an inappropriately-activated immune response.

  17. Redox buffered hydrofluoric acid etchant for the reduction of galvanic attack during release etching of MEMS devices having noble material films

    Science.gov (United States)

    Hankins, Matthew G.

    2009-10-06

    Etchant solutions comprising a redox buffer can be used during the release etch step to reduce damage to the structural layers of a MEMS device that has noble material films. A preferred redox buffer comprises a soluble thiophosphoric acid, ester, or salt that maintains the electrochemical potential of the etchant solution at a level that prevents oxidation of the structural material. Therefore, the redox buffer preferentially oxidizes in place of the structural material. The sacrificial redox buffer thereby protects the exposed structural layers while permitting the dissolution of sacrificial oxide layers during the release etch.

  18. Drug Release Property of Modified Hyaluronic Acid Films in Vitro%改性透明质酸薄膜的体外释药性能研究

    Institute of Scientific and Technical Information of China (English)

    聂素云

    2012-01-01

    OBJECTIVE To evaluate the in vitro drug release properties of modified hyaluronic acid films. METHODS The drug release rates of the films were measured by dictyo-dish method and UV-Vis absorption spectroscopy. The effects of modifier contents and the solubility of medicines on the release were investigated. RESULTS The release of some hydrophobic drugs from the films were sustained. The drug release pattern followed Higuchi equation, and was controlled by diffusion mechanism. Drug release rates were delayed by increasing contents of modifier. CONCLUSION The films made of modified hyaluronic acid have excellent potentials as carriers for the sustained release of some hydrophobic drugs.%目的 对改性透明质酸制备的载药薄膜进行体外药物释放研究,为制备良好的缓释制剂提供参考依据.方法 用网碟法及紫外分光光度法测定载药薄膜的药物体外释放度,考查了改性剂用量和药物溶解性对释放度的影响.结果 载药薄膜对非水溶性药物具有较好的缓释作用,药物的体外释放符合Higuchi公式,受扩散机制控制.增加改性剂的用量可以降低药物的释放速率.结论 改性透明质酸薄膜对疏水性药物具有较好的缓释作用,是一种良好的药物载体.

  19. Activation of platelet aggregation and arachidonate metabolism in early stage of acute radiation injury

    International Nuclear Information System (INIS)

    The paper describes the changes of platelet aggregation and arachidonate metabolism in platelets and endothelial cells after 8.0-8.5 Gy γ-ray whole-body irradiation in rats. It was found that with 8.0 Gy exposure platelet aggregation rate and speed, and plasma TxB2 level were increased at 4h and on the 1st day post irradiation, and that 6-keto-PGF1α level was enhanced at 4h, then reduced to the control level on the 1st day post irradiation. The result of biological assay showed the ability for rat platelets to convert exogenous arachidonate into TxA2 was significantly raised at 4h and on the 1st day after 8.5 Gy γ-ray irradiation. It is suggested that the activation of platelet arachidonate metabolism may be one of the important causes of acute radiation injury is suggested that the activation of platelet arachidonate metabolism may be one of the important causes of acute radiation injury

  20. Sustained Release of Hydrophilic l-ascorbic acid 2-phosphate Magnesium from Electrospun Polycaprolactone Scaffold—A Study across Blend, Coaxial, and Emulsion Electrospinning Techniques

    Directory of Open Access Journals (Sweden)

    Xinxin Zhao

    2014-11-01

    Full Text Available The purpose of this study was to achieve a sustained release of hydrophilic l-ascorbic acid 2-phosphate magnesium (ASP from electrospun polycaprolactone (PCL scaffolds, so as to promote the osteogenic differentiation of stem cells for bone tissue engineering (TE. ASP was loaded and electrospun together with PCL via three electrospinning techniques, i.e., coaxial, emulsion, and blend electrospinning. For blend electrospinning, binary solvent systems of dichloromethane–methanol (DCM–MeOH and dichloromethane–dimethylformamide (DCM–DMF were used to achieve the desired ASP release through the effect of solvent polarity and volatility. The scaffold prepared via a blend electrospinning technique with a binary solvent system of DCM–MeOH at a 7:3 ratio demonstrated a desirable, sustained ASP release profile for as long as two weeks, with minimal burst release. However, an undesirable burst release (~100% was observed within the first 24 h for scaffolds prepared by coaxial electrospinning. Scaffolds prepared by emulsion electrospinning displayed poorer mechanical properties. Sustained releasing blend electrospun scaffold could be a good potential candidate as an ASP-eluting scaffold for bone tissue engineering.

  1. Is the release of acid phosphatases by ectomycorrhizal fungi a matter of environmental conditions or species in situ?

    OpenAIRE

    Plassard, Claude; Ali, Muhhammad A.; Duchemin, Myriam; Legname-Vonarx, Elvira; Louche, Julien; Cloutier-Hurteau, Benoît

    2011-01-01

    Ectomycorrhizal (ECM) fungi are able to release significant amounts of phosphatases (Pases) in their environment. These enzymes, by releasing the phosphate group of organic P, may play an important role in the recycling of P in forest soil. However, whether this enzyme release depends on the fungal diversity and / or the nutrient availability is not known. We addressed this question in the maritime pine (Pinus pinaster) forest, the first planted area in France on sandy podzol very poor in ...

  2. Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury.

    Science.gov (United States)

    Khalaf, Aseel; Babiker, Fawzi

    2016-09-01

    We and others have demonstrated a protective effect of pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury. However, the mechanisms underlying this protection are not completely clear. In the present study, we evaluated the effects of calcium release from the sarcoplasmic reticulum (SR) and the novel intracellular acidic stores (AS). Isolated rat hearts (n = 6 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Cardiac hemodynamics and contractility were assessed using a data acquisition program, and cardiac injury was evaluated by creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. The hearts were also subjected to PPC (3 cycles of 30 s of left ventricle (LV) pacing alternated with 30 s of right atrium (RA) pacing) and/or were treated during reperfusion with agonists or antagonists of release of calcium from SR or AS. PPC significantly (P < 0.05) normalized LV, contractility, and coronary vascular dynamics and significantly (P < 0.001) decreased heart enzyme levels compared to the control treatments. The blockade of SR calcium release resulted in a significant (P < 0.01) recovery in LV function and contractility and a significant reduction in CK and LDH levels (P < 0.01) when applied alone or in combination with PPC. Interestingly, the release of calcium from AS alone or in combination with PPC significantly improved LV function and contractility (P < 0.05) and significantly decreased the CK and LDH levels (P < 0.01) compared to the control treatments. An additive effect was produced when agonism of calcium release from AS or blockade of calcium release from the SR was combined with PPC. Calcium release from AS and blockade of calcium release from the SR protect the heart against I

  3. The release of dipicolinic acid--the rate-limiting step of Bacillus endospore inactivation during the high pressure thermal sterilization process.

    Science.gov (United States)

    Reineke, Kai; Schlumbach, Karl; Baier, Daniel; Mathys, Alexander; Knorr, Dietrich

    2013-03-01

    High pressure combined with elevated temperatures can produce low acid, commercially sterile and shelf-stable foods. Depending on the temperature and pressure levels applied, bacterial endospores pass through different pathways, which can lead to a pressure-induced germination or inactivation. Regardless of the pathway, Bacillus endospores first release pyridine-2,6-dicarboxylic acid (DPA), which contributes to the low amount of free water in the spore core and is consequently responsible for the spore's high resistance against wet and dry heat. This is therefore the rate-limiting step in the high pressure sterilization process. To evaluate the impact of a broad pressure, temperature and time domain on the DPA release, Bacillus subtilis spores were pressure treated between 0.1 and 900 MPa at between 30 and 80 °C under isothermal isobaric conditions during dwell time. DPA quantification was assessed using HPLC, and samples were taken both immediately and 2 h after the pressure treatment. To obtain a release kinetic for some pressure-temperature conditions, samples were collected between 1s and 60 min after decompression. A multiresponse kinetic model was then used to derive a model covering all kinetic data. The isorate lines modeled for the DPA release in the chosen pressure-temperature landscape enabled the determination of three distinct zones. (I) For pressures temperatures >50 °C, a 90% DPA release was achievable in less than 5 min and no difference in the amount of DPA was found immediately 2 h after pressurization. This may indicate irreversible damage to the inner spore membrane or membrane proteins. (II) Above 600 MPa the synergism between pressure and temperature diminished, and the treatment temperature alone dominated DPA release. (III) Pressures temperatures <50 °C resulted in a retarded release of DPA, with strong increased differences in the amount of DPA released after 2 h, which implies a pressure-induced physiological like germination with

  4. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid--an experimental study in rats.

    OpenAIRE

    Schliephake, Henning; Weich, Herbert A.; Dullin, Christian; Gruber, Rudolf; Frahse, Sarah

    2008-01-01

    The aim of the present study was to test the hypothesis that human recombinant bone morphogenic protein 2 (rhBMP-2) implanted in a slow release carrier of polylactic acid (PLA) can repair a non-healing defect in the rat mandible and maintain the thickness of an augmented volume. p-DL-lactic acid discs were produced and loaded with 48 and 96 microg rhBMP-2 and inserted into non-healing defects of the mandible of 45 Wistar rats. Fifteen rats received implants with 96 microg rhBMP-2 (Group 2), 4...

  5. Release and swelling studies of an innovative antidiabetic-bile acid microencapsulated formulation, as a novel targeted therapy for diabetes treatment.

    Science.gov (United States)

    Mooranian, Armin; Negrulj, Rebecca; Al-Sallami, Hesham S; Fang, Zhongxiang; Mikov, Momir; Golocorbin-Kon, Svetlana; Fakhoury, Marc; Arfuso, Frank; Aruso, Frank; Al-Salami, Hani

    2015-01-01

    In previous studies carried out in our laboratory, a bile acid formulation exerted a hypoglycaemic effect in a rat model of type 1 diabetes (T1D). When the antidiabetic drug gliclazide was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-deoxycholic acid (G-DCA), with good structural properties, excipient compatibility and which exhibited pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH controlled properties of this new formulation. The aim is also to examine the effect of DCA on G release kinetics at various pH values and different temperatures. Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared including: G-SA (control) and G-DCA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, 3, 7.4 and 7.8 and temperatures of 25 °C and 37 °C. The new formulation is further optimised by the addition of DCA. DCA reduced bead-swelling of the microcapsules at pH 7.8 and 3 at 25 °C and 37 °C, and even though bead size remains similar after DCA addition, the percentage of G release was enhanced at high pH values (pH 7.4 and 7.8, p < 0.01). The new formulation exhibits colon-targeted delivery and the addition of DCA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and DCA to the lower intestine. PMID:25265061

  6. Fliposomes: pH-Sensitive Liposomes Containing a trans-2-morpholinocyclohexanol-Based Lipid That Performs a Conformational Flip and Triggers an Instant Cargo Release in Acidic Medium

    OpenAIRE

    Barbora Brazdova; Franz, Andreas H.; Samoshin, Vyacheslav V.; Xin Guo; Xin Liu; Samoshina, Nataliya M.

    2011-01-01

    Incorporation of a pH-sensitive conformational switch into a lipid structure enables a drastic conformational flip upon protonation that disrupts the liposome membrane and causes rapid release of cargo specifically in areas of increased acidity. pH-sensitive liposomes containing the amphiphile (1) with trans-2-morpholinocyclohexanol conformational switch, a phospholipid, and a PEG-lipid conjugate were constructed and characterized. The optimized composition—1/POPC/PEG-ceramide (50/45/5)—could...

  7. Differential free fatty acid receptor-1 (FFAR1/GPR40) signalling is associated with gene expression or gelatinase granule release in bovine neutrophils.

    Science.gov (United States)

    Mena, Sandra J; Manosalva, Carolina; Carretta, Maria D; Teuber, Stefanie; Olmo, Iván; Burgos, Rafael A; Hidalgo, Maria A

    2016-08-01

    Fatty acids have been recognized as regulators of immune function in addition to their known metabolic role. Long-chain fatty acids bind free fatty acid receptor (FFAR)-1/GPR40, which is expressed on bovine neutrophils, and increase responses such as granule release and gene expression. In this study, we investigated the molecular mechanisms governing the up-regulation of cyclooxygenase-2 (COX-2) and IL-8, as well as matrix metalloproteinase (MMP)-9 granule release in FFAR1/GPR40 agonist-stimulated neutrophils. Our results showed that natural (oleic and linoleic acid) and synthetic (GW9508) FFAR1/GPR40 agonists increased ERK1/2, p38 MAPK and Akt phosphorylation, and that the FFAR1/GPR40 antagonist GW1100 reduced these responses. We evaluated the levels of IκBα, a component of the classical activation pathway of the transcription factor NF-κB, and we observed IκBα reduction after stimulation with FFAR1/GPR40 agonists, an effect that was inhibited by GW1100 or the inhibitors UO126, SB203580 or LY294002. FFAR1/GPR40 agonists increased COX-2 and IL-8 expression, which was inhibited by GW1100 and an NF-κB inhibitor. Finally, the FFAR1/GPR40 agonist-induced MMP-9 granule release was reduced by GW1100 and UO126. In conclusion, FFAR1/GPR40 agonists differentially stimulate neutrophil functions; COX-2 and IL-8 are expressed after FFAR1/GPR40 activation via NF-κB, IκBα reduction is FFAR1/GPR40- and PI3K/MAPK-dependent, and MMP-9 granule release is FFAR1/GPR40- and ERK1/2-dependent. PMID:27363707

  8. Antidepressant Potential of Chlorogenic Acid-Enriched Extract from Eucommia ulmoides Oliver Bark with Neuron Protection and Promotion of Serotonin Release through Enhancing Synapsin I Expression

    Directory of Open Access Journals (Sweden)

    Jianming Wu

    2016-02-01

    Full Text Available Eucommia ulmoides Oliver (E. ulmoides is a traditional Chinese medicine with many beneficial effects, used as a tonic medicine in China and other countries. Chlorogenic acid (CGA is an important compound in E. ulmoides with neuroprotective, cognition improvement and other pharmacological effects. However, it is unknown whether chlorogenic acid-enriched Eucommia ulmoides Oliver bark has antidepressant potential through neuron protection, serotonin release promotion and penetration of blood-cerebrospinal fluid barrier. In the present study, we demonstrated that CGA could stimulate axon and dendrite growth and promote serotonin release through enhancing synapsin I expression in the cells of fetal rat raphe neurons in vitro. More importantly, CGA-enriched extract of E. ulmoides (EUWE at 200 and 400 mg/kg/day orally administered for 7 days showed antidepressant-like effects in the tail suspension test of KM mice. Furthermore, we also found CGA could be detected in the the cerebrospinal fluid of the rats orally treated with EUWE and reach the level of pharmacological effect for neuroprotection by UHPLC-ESI-MS/MS. The findings indicate CGA is able to cross the blood-cerebrospinal fluid barrier to exhibit its neuron protection and promotion of serotonin release through enhancing synapsin I expression. This is the first report of the effect of CGA on promoting 5-HT release through enhancing synapsin I expression and CGA-enriched EUWE has antidepressant-like effect in vivo. EUWE may be developed as the natural drugs for the treatment of depression.

  9. Influence of the composition of hydroxypropyl cellulose/maleic acid-alt-styrene copolymer blends on their properties as matrix for drug release

    Directory of Open Access Journals (Sweden)

    2009-05-01

    Full Text Available Poly(carboxylic acid-polysaccharide compositions have been found suitable for obtaining drug formulations with controlled release, most formulations being therapeutically efficacious, stable, and non-irritant. The influence of the characteristics of the aqueous solutions from which the polymer matrix is prepared (i.e. the total concentration of polymer in solutions and the mixing ratio between the partners, hydroxypropyl cellulose, HPC and maleic acid-alternating-styrene copolymer, MAc-alt-S on the kinetics of some drugs release in acidic environment (pH = 2 has been followed by ‘in vitro’ dissolution tests. It has been established that the kinetics of procaine hydrochloride release from HPC/MAc-alt-S matrix depends on its composition; the diffusion exponent, n is close to 0.5 for matrices where one of the components is in large excess and n~0.02 for middle composition range. The lower value of diffusion exponent for middle composition range could be caused by the so called ‘burst effect’, therefore the kinetic evaluation is difficult.

  10. Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

    OpenAIRE

    P.C. Calder

    1998-01-01

    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...

  11. Chemical design of pH-sensitive nanovalves on the outer surface of mesoporous silicas for controlled storage and release of aromatic amino acid

    International Nuclear Information System (INIS)

    Mesoporous silicas with hexagonally arranged pore channels were synthesized in water–ethanol-ammonia solution using cetyltrimethylammonium bromide as template. Directed modification of silica surface with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups was realized by postsynthetic activation of halogenoalkylsilicas, which have surface uniformly or selectively distributed 3-chloropropyl groups, with 2-aminodiphenylamine in the liquid phase. Chemical composition of silica materials was estimated by IR spectroscopy and chemical analysis of the surface products of reactions. Characteristics of porous structure of MCM-41-type silicas were determined from X-ray and low-temperature nitrogen ad-desorption measurements. Release ability of synthesized silica carriers was established on encapsulation of 4-aminobenzoic acid in pore channels and subsequent delivery at pH=6.86 and pH=1.00. It was found that N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups block pore entrances at neutral pH preventing 4-aminobenzoic acid release. At pH=1.00 repulsion of positively charged surface aromatic amino groups localized near pore orifices provides unhindered liberation of aromatic amino acid from mesoporous channels. - Graphical abstract: Blocking of pores with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups at pH=6.86 for storage of ABA and opening of pore entrances at pH=1.00 for unhindered ABA liberation. - Highlights: • Modification of MCM-41 with N-[N -(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups. • Study of release ability of synthesized silica carriers in relation to amino acid. • Controlled blocking and opening of pores by amino groups at pH change were performed. • Retention of amino acid at pH=6.86 and its liberation at pH=1.00 was proved

  12. Effect of desferrioxamine B and Suwannee River fulvic acid on Fe(III) release and Cr(III) desorption from goethite

    Science.gov (United States)

    Stewart, Angela G.; Hudson-Edwards, Karen A.; Dubbin, William E.

    2016-04-01

    Siderophores are biogenic chelating ligands that facilitate the solubilisation of Fe(III) and form stable complexes with a range of contaminant metals and therefore may significantly affect their biogeochemical cycling. Desferrioxamine B (DFOB) is a trihydroxamate siderophore that acts synergistically with fulvic acid and low molecular weight organic ligands to release Fe from Fe(III) oxides. We report the results of batch dissolution experiments in which we determine the rates of Cr(III) desorption and Fe(III) release from Cr(III)-treated synthetic goethite as influenced by DFOB, by fulvic acid, and by the two compounds in combination. We observed that adsorbed Cr(III) at 3% surface coverage significantly reduced Fe(III) release from goethite for all combinations of DFOB and fulvic acid. When DFOB (270 μM) was the only ligand present, dissolved Fe(III) and Cr(III) increased approximately 1000-fold and 16-fold, respectively, as compared to the ligand-free system, a difference we attribute to the slow rate of water exchange of Cr(III). Suwannee River fulvic acid (SRFA) acts synergistically with DFOB by (i) reducing the goethite surface charge leading to increased HDFOB+ surface excess and by (ii) forming aqueous Fe(III)-SRFA species whose Fe(III) is subsequently removed by DFOB to yield aqueous Fe(III)-DFOB complexes. These observations shed new light on the synergistic relationship between DFOB and fulvic acid and reveal the mechanisms of Fe(III) acquisition available to plants and micro-organisms in Cr(III) contaminated environments.

  13. Chemical design of pH-sensitive nanovalves on the outer surface of mesoporous silicas for controlled storage and release of aromatic amino acid

    Energy Technology Data Exchange (ETDEWEB)

    Roik, N.V., E-mail: roik_nadya@ukr.net; Belyakova, L.A.

    2014-07-01

    Mesoporous silicas with hexagonally arranged pore channels were synthesized in water–ethanol-ammonia solution using cetyltrimethylammonium bromide as template. Directed modification of silica surface with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups was realized by postsynthetic activation of halogenoalkylsilicas, which have surface uniformly or selectively distributed 3-chloropropyl groups, with 2-aminodiphenylamine in the liquid phase. Chemical composition of silica materials was estimated by IR spectroscopy and chemical analysis of the surface products of reactions. Characteristics of porous structure of MCM-41-type silicas were determined from X-ray and low-temperature nitrogen ad-desorption measurements. Release ability of synthesized silica carriers was established on encapsulation of 4-aminobenzoic acid in pore channels and subsequent delivery at pH=6.86 and pH=1.00. It was found that N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups block pore entrances at neutral pH preventing 4-aminobenzoic acid release. At pH=1.00 repulsion of positively charged surface aromatic amino groups localized near pore orifices provides unhindered liberation of aromatic amino acid from mesoporous channels. - Graphical abstract: Blocking of pores with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups at pH=6.86 for storage of ABA and opening of pore entrances at pH=1.00 for unhindered ABA liberation. - Highlights: • Modification of MCM-41 with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups. • Study of release ability of synthesized silica carriers in relation to amino acid. • Controlled blocking and opening of pores by amino groups at pH change were performed. • Retention of amino acid at pH=6.86 and its liberation at pH=1.00 was proved.

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

    International Nuclear Information System (INIS)

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

  15. Controlled Release of Linalool Using Nanofibrous Membranes of Poly(lactic acid) Obtained by Electrospinning and Solution Blow Spinning: A Comparative Study.

    Science.gov (United States)

    Souza, Michelle A; Oliveira, Juliano E; Medeiros, Eliton S; Glenn, Gregory M; Mattoso, Luiz H C

    2015-08-01

    The controlled-release of natural plant oils such as linalool is of interest in therapeutics, cosmetics, and antimicrobial and larvicidal products. The present study reports the release characteristics of linalool encapsulated at three concentrations (10, 15 and 20 wt.%) in poly(lactic acid) nanofibrous membranes produced by electrospinning and solution blow spinning (SBS) as well as the effect of linalool on fiber morphology and structural properties. PLA nanofibrous membranes were characterized by Scanning Electron Microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and contact angle measurements. The average diameters of the electrospun and solution blow spun nanofibers were similar, ranging from 176 to 240 nm. Linalool behaved as a plasticizer to PLA decreasing the glass transition temperature (Tg), melting point (Tm) and crystallization temperature (TC) of PLA. Curves of the release of linalool at 35 °C were non-linear, showing a clear biphasic pattern consistent with one or more Fickian release components. The time required to release 50% of linalool (t1/2) decreased with increasing linalool concentration. The range in t1/2 values for SBS nanofibers was higher (291-1645s) than the t1/2 values for electrospun fibers (76-575s). PMID:26369129

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-09

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

  17. The role of hyaluronic acid inclusion on the energetics of encapsulation and release of a protein molecule from chitosan-based nanoparticles.

    Science.gov (United States)

    Al-Qadi, Sonia; Alatorre-Meda, Manuel; Martin-Pastor, Manuel; Taboada, Pablo; Remuñán-López, Carmen

    2016-05-01

    The synergistic effects of the polysaccharides chitosan (CS) and hyaluronic acid (HA) formulated into hybrid nanoparticles are promising for drug delivery. In the present work, we performed a detailed analysis of the molecular interactions involved in the TPP-assisted ionotropic gelation of CS hybrid nanoparticles with the objective of investigating the impact of HA inclusion on the particle formulation and on the in vitro release of insulin (INS) as a protein cargo. To do that, an in-depth thermodynamic study was carried out by isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. Such analysis allowed us to elucidate the type and extent of interactions established by INS within the hybrid nanoparticles and to get further knowledge on the nature of its release mechanism in vitro. Overall, INS release from the CS nanoparticles was thermodynamically driven, and when including HA a weaker INS binding to the nanoparticles, hence, a faster release rate in vitro were observed. As a negative polyelectrolyte, HA might have sterically blocked the activated sites of CS, such as the amino groups, through chain entanglement, thereby, attenuating the competitive binding interactions of INS. As a consequence, INS might have experienced a spatial exclusion onto the surface of the hybrid nanoparticles to a greater extent which, in turn, would explain its initial abrupt release. PMID:26854581

  18. Metabolomics of dietary fatty acid restriction in patients with phenylketonuria.

    Directory of Open Access Journals (Sweden)

    Ulrike Mütze

    Full Text Available BACKGROUND: Patients with phenylketonuria (PKU have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA. Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. METHODOLOGY/PRINCIPAL FINDINGS: 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6-C18 in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS. Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re- absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6 a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B(2 and thromboxane B(3 release did not differ from that of healthy controls. CONCLUSION/SIGNIFICANCE: Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta

  19. A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin

    Science.gov (United States)

    Khatun, Zehedina; Nurunnabi, Md; Nafiujjaman, Md; Reeck, Gerald R.; Khan, Haseeb A.; Cho, Kwang Jae; Lee, Yong-Kyu

    2015-06-01

    The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid

  20. In vitro release studies of vitamin B12 from poly N-vinyl pyrrolidone /starch hydrogels grafted with acrylic acid synthesized by gamma radiation

    International Nuclear Information System (INIS)

    Co-polymeric hydrogels containing N-vinyl pyrrolidone and starch grafted with acrylic acid were synthesized by gamma radiation. Their gel contents, grafting process and swelling were evaluated. The gels were also characterized by thermal gravimetric analysis. The gel content found to be increase with increasing the irradiation dose up to 50 kGy then decrease. The grafting percent increase by increasing the percentage of acrylic acid in the grafted hydrogels. The thermal stability and the rate of the thermal decomposition showed to be changed according to the different composition of the hydrogels. It also showed a decrease in the maximum rate of the thermal decomposition by the increasing of the irradiation dose from 20 to 30 kGy and increases by increasing the irradiation dose from 30 to 70 kGy. The hydrogels loaded with vitamin B12 as drug model, demonstrated a decrease release in acidic medium than the neutral one