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Sample records for acid induces selective

  1. Selective charging of tRNA isoacceptors induced by amino-acid starvation

    DEFF Research Database (Denmark)

    Dittmar, K. A.; Sørensen, Michael Askvad; Elf, J.;

    2005-01-01

    -acid starvation results in 'selective charging' where the charging levels of some tRNA isoacceptors will be low and those of others will remain high. Here, we developed a microarray for the analysis of charged fractions of tRNAs and measured charging for all Escherichia coli tRNAs before and during leucine......, threonine or arginine starvation. Before starvation, most tRNAs were fully charged. During starvation, the isoacceptors in the leucine, threonine or arginine families showed selective charging when cells were starved for their cognate amino acid, directly confirming the theoretical prediction. Codons read...

  2. Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells induced by retinoic acid receptor- and retinoid X receptor-selective retinoic acid analogs.

    Science.gov (United States)

    Brooks, S C; Kazmer, S; Levin, A A; Yen, A

    1996-01-01

    The ability of subtypes of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) singly and in combination to elicit myeloid differentiation, G1/0-specific growth arrest, and retinoblastoma (RB) tumor suppressor protein dephosphorylation was determined in the human myeloblastic leukemia cell line HL-60 using subtype-selective retinoic acid (RA) analogs. RA analogs that selectively bind only to RARs (Am580 and/or TTNPB) or to RXRs (Ro 25-6603, SR11237, and/or SR11234) did not elicit the above-mentioned three cellular responses. In contrast, simultaneous treatment with both an RAR-selective ligand (Am580 or TTNPB) and an RXR-selective ligand (Ro 25-6603, SR11237, or SR11234) induced all three cellular processes. An RAR alpha-selective ligand used with an RXR-selective ligand generated the same responses as did all-trans RA or 9-cis RA, which affect both families of receptors, suggesting an important role for RAR alpha among RAR subtypes in eliciting cellular response. Consistent with this finding, the RAR alpha antagonist, Ro 41-5253, reduced the level of the cellular responses elicited by treatment with an RAR alpha-selective ligand plus RXR-selective ligand. The coupling of the shift of RB to its hypophosphorylated form with G1/0 arrest and differentiation in response to ligands is consistent with a possible role of RB as a downstream target or effector of RAR alpha and RXR in combination.

  3. Ligand-induced substrate steering and reshaping of [Ag2(H)](+) scaffold for selective CO2 extrusion from formic acid.

    Science.gov (United States)

    Zavras, Athanasios; Khairallah, George N; Krstić, Marjan; Girod, Marion; Daly, Steven; Antoine, Rodolphe; Maitre, Philippe; Mulder, Roger J; Alexander, Stefanie-Ann; Bonačić-Koutecký, Vlasta; Dugourd, Philippe; O'Hair, Richard A J

    2016-01-01

    Metalloenzymes preorganize the reaction environment to steer substrate(s) along the required reaction coordinate. Here, we show that phosphine ligands selectively facilitate protonation of binuclear silver hydride cations, [LAg2(H)](+) by optimizing the geometry of the active site. This is a key step in the selective, catalysed extrusion of carbon dioxide from formic acid, HO2CH, with important applications (for example, hydrogen storage). Gas-phase ion-molecule reactions, collision-induced dissociation (CID), infrared and ultraviolet action spectroscopy and computational chemistry link structure to reactivity and mechanism. [Ag2(H)](+) and [Ph3PAg2(H)](+) react with formic acid yielding Lewis adducts, while [(Ph3P)2Ag2(H)](+) is unreactive. Using bis(diphenylphosphino)methane (dppm) reshapes the geometry of the binuclear Ag2(H)(+) scaffold, triggering reactivity towards formic acid, to produce [dppmAg2(O2CH)](+) and H2. Decarboxylation of [dppmAg2(O2CH)](+) via CID regenerates [dppmAg2(H)](+). These gas-phase insights inspired variable temperature NMR studies that show CO2 and H2 production at 70 °C from solutions containing dppm, AgBF4, NaO2CH and HO2CH. PMID:27265868

  4. Apoptosis selectively induced in BEL-7402 cells by folic acid-modified magnetic nanoparticles combined with 100 Hz magnetic field

    Directory of Open Access Journals (Sweden)

    Wen J

    2014-04-01

    Full Text Available Jian Wen,1 Shulian Jiang,1 Zhiqiang Chen,1 Wei Zhao,1 Yongxiang Yi,1 Ruili Yang,1 Baoan Chen2 1Second Affiliated Hospital of Southeast University, 2Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China Objective: To explore the effect of folic acid-modified magnetic nanoparticles (FA-MNPs combined with a 100 Hz extremely low-frequency electromagnetic field (ELF-EMF on the apoptosis of liver cancer BEL-7402 cells. Materials and methods: MNPs (20 nm were prepared by coprecipitation, and then folic acid was coated onto MNPs to prepare FA-MNPs. BEL-7402 cells and HL7702 cells were selected as liver cancer cells and normal liver cells, respectively. The ELF-EMF was generated from a solenoid coil. Cellular uptake of NPs was determined by inductively coupled plasma atomic emission spectroscopy. A 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay was used to evaluate cell inhibition. Apoptosis was analyzed by flow cytometry. Statistical analyses were performed using two-way analysis of variance. Results: FA-MNPs combined with a 100 Hz magnetic field significantly inhibited cell proliferation and induced higher apoptosis compared to either the ELF-EMF alone or FA-MNPs alone. FA-MNPs showed a better apoptosis effect and higher iron uptake in BEL-7402 cells compared to in HL7702 cells. On the basis of the ELF-EMF, higher doses of FA-MNPs brought higher apoptosis and higher iron uptake in either BEL-7402 cells or HL7702 cells. Conclusion: These results suggest that FA-MNPs may induce apoptosis in a cellular iron uptake-dependent manner when combined with an ELF-EMF in BEL-7402 cells.Keywords: extremely low-frequency magnetic field, magnetic nanoparticle, apoptosis, liver cancer, folic acid

  5. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers

    Science.gov (United States)

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-01

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

  6. Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Thomas Galbo

    Full Text Available In type 2 Diabetes (T2D free fatty acids (FFAs in plasma are increased and hepatic insulin resistance is "selective", in the sense that the insulin-mediated decrease of glucose production is blunted while insulin's effect on stimulating lipogenesis is maintained. We investigated the molecular mechanisms underlying this pathogenic paradox. Primary rat hepatocytes were exposed to palmitate for twenty hours. To establish the physiological relevance of the in vitro findings, we also studied insulin-resistant Zucker Diabetic Fatty (ZDF rats. While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1 was inhibited in palmitate-exposed cells. Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. In contrast, similar to findings in human T2D, the ability of insulin to induce triglyceride (TG accumulation and transcription of the enzymes that catalyze de novo lipogenesis and TG assembly was unaffected. Insulin-induction of these genes could, however, be blocked by inhibition of the atypical PKCs (aPKCs. The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A was increased in the insulin-resistant cells. Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity.

  7. 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.

  8. Urea derivates of ursolic, oleanolic and maslinic acid induce apoptosis and are selective cytotoxic for several human tumor cell lines.

    Science.gov (United States)

    Sommerwerk, Sven; Heller, Lucie; Kuhfs, Julia; Csuk, René

    2016-08-25

    2,3-Di-O-acetyl-maslinic acid benzylamide (5) has previously been shown to possess high cytotoxicity for a variety of human tumor cell lines while being of low cytotoxicity to non-malignant cells. Structural modifications performed on 5 revealed that the presence of these acetyl groups in 5 and the presence of (2β,3β)-configurated centers seems necessary for obtaining high cytotoxicity combined with best selectivity between malignant cells and non-malignant mouse fibroblasts. Compounds carrying an ursane skeleton showed weaker cytotoxicity than their oleanane derived analogs. In addition, the benzylamide function in compound 5 should be replaced by a phenylurea moiety to gain better cytotoxicity while retaining and improving the selectivity. Thus, maslinic acid derived N-[2β,3β-di-O-acetyl-17β-amino-28-norolean-12-en-17-yl]phenylurea (45) gave best results showing EC50 = 0.9 μM (for A2780 ovarian cancer cells) with EC50 > 120 μM for fibroblasts (NIH 3T3) and triggered apoptosis while caspase-3 was not activated by this compound.

  9. Single substitutions to closely related amino acids contribute to the functional diversification of an insect-inducible, positively selected plant cystatin.

    Science.gov (United States)

    Rasoolizadeh, Asieh; Goulet, Marie-Claire; Sainsbury, Frank; Cloutier, Conrad; Michaud, Dominique

    2016-04-01

    A causal link has been reported between positively selected amino acids in plant cystatins and the inhibitory range of these proteins against insect digestive cysteine (Cys) proteases. Here we assessed the impact of single substitutions to closely related amino acids on the contribution of positive selection to cystatin diversification. Cystatin sequence alignments, while confirming hypervariability, indicated a preference for related amino acids at positively selected sites. For example, the non-polar residues leucine (Leu), isoleucine (Ile) and valine (Val) were shown to predominate at positively selected site 2 in the N-terminal region, unlike selected sites 6 and 10, where polar residues are preferred. The model cystatin SlCYS8 and single variants with Leu, Ile or Val at position 2 were compared with regard to their ability to bind digestive proteases of the coleopteran pest Leptinotarsa decemlineata and to induce compensatory responses in this insect. A functional proteomics procedure to capture target Cys proteases in midgut extracts allowed confirmation of distinct binding profiles for the cystatin variants. A shotgun proteomics procedure to monitor whole Cys protease complements revealed protease family specific compensatory responses in the insect, dependent on the variant ingested. Our data confirm the contribution of closely related amino acids to the functional diversity of positively selected plant cystatins in a broader structure/function context imposing physicochemical constraints to primary structure alterations. They also underline the complexity of protease/inhibitor interactions in plant-insect systems, and the challenges still to be met in order to harness the full potential of ectopically expressed protease inhibitors in crop protection.

  10. Epigenetic priming of AML blasts for all-trans retinoic acid-induced differentiation by the HDAC class-I selective inhibitor entinostat.

    Directory of Open Access Journals (Sweden)

    Nadja Blagitko-Dorfs

    Full Text Available All-trans retinoic acid (ATRA has only limited single agent activity in AML without the PML-RARα fusion (non-M3 AML. In search of a sensitizing strategy to overcome this relative ATRA resistance, we investigated the potency of the HDAC class-I selective inhibitor entinostat in AML cell lines Kasumi-1 and HL-60 and primary AML blasts. Entinostat alone induced robust differentiation of both cell lines, which was enhanced by the combination with ATRA. This "priming" effect on ATRA-induced differentiation was at least equivalent to that achieved with the DNA hypomethylating agent decitabine, and could overall be recapitulated in primary AML blasts treated ex vivo. Moreover, entinostat treatment established the activating chromatin marks acH3, acH3K9, acH4 and H3K4me3 at the promoter of the RARβ2 gene, an essential mediator of retinoic acid (RA signaling in different solid tumor models. Similarly, RARβ2 promoter hypermethylation (which in primary blasts from 90 AML/MDS patients was surprisingly infrequent could be partially reversed by decitabine in the two cell lines. Re-induction of the epigenetically silenced RARβ2 gene was achieved only when entinostat or decitabine were given prior to ATRA treatment. Thus in this model, reactivation of RARβ2 was not necessarily required for the differentiation effect, and pharmacological RARβ2 promoter demethylation may be a bystander phenomenon rather than an essential prerequisite for the cellular effects of decitabine when combined with ATRA. In conclusion, as a "priming" agent for non-M3 AML blasts to the differentiation-inducing effects of ATRA, entinostat is at least as active as decitabine, and both act in part independently from RARβ2. Further investigation of this treatment combination in non-M3 AML patients is therefore warranted, independently of RARβ2 gene silencing by DNA methylation.

  11. Selective surface functionalization of polystyrene induced by synchrotron or UV radiation in the presence of oxygen or acrylic acid vapors

    International Nuclear Information System (INIS)

    Efficient surface functionalization of Polystyrene (PS) thin films by electromagnetic radiation in combination with a reactive gaseous atmosphere was obtained. Monochromatic synchrotron (SR) or polychromatic UV radiation were used as excitation sources. When SR was used, O2 was introduced after irradiation into the UHV chamber. UV irradiation was carried out keeping a constant flow of O2 or acrylic acid (AA) vapors during the photolysis. FTIR-ATR and XPS-NEXAFS spectra were obtained at the UFRGS and the LNLS, Campinas respectively. PS films were functionalized by monochromatic SR and then expose to O2 at specific transitions such us C 1s →σ*C-C excitation. It was found a high rate of COO, C=O and C-O groups at the surface (> 70%). UV-assisted treatment in the presence of AA vapors showed that an efficient polymerization process took place, such as, it was observed in previous AA low pressure RF plasma treatments. UV-assisted functionalization has the advantage of lower costs and simple set-up compared to plasma treatments. (author)

  12. A highly selective turn-on fluorescent probe for hypochlorous acid based on hypochlorous acid-induced oxidative intramolecular cyclization of boron dipyrromethene-hydrazone

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei-Chieh; Venkatesan, Parthiban; Wu, Shu-Pao, E-mail: spwu@mail.nctu.edu.tw

    2015-07-02

    Highlights: • A BODIPY-based fluorescent probe for sensing HOCl was developed. • The probe utilizes the HOCl-promoted cyclization in response to the amount of HOCl. • The probe might have application in the investigation of HOCl in biological systems. - Abstract: A BODIPY-based fluorescent probe, HBP, was developed for the detection of hypochlorous acid based on the specific hypochlorous acid-promoted oxidative intramolecular cyclization of heterocyclic hydrazone in response to the amount of HOCl. The reaction is accompanied by a 41-fold increase in the fluorescent quantum yield (from 0.004 to 0.164). The fluorescence intensity of the reaction between HOCl and HBP is linear in the HOCl concentration range of 1–8 μM with a detection limit of 2.4 nM (S/N = 3). Confocal fluorescence microscopy imaging using RAW264.7 cells showed that the new probe HBP could be used as an effective fluorescent probe for detecting HOCl in living cells.

  13. Fatty acid content of selected seed oils.

    Science.gov (United States)

    Orhan, Ilkay; Sener, Bilge

    2002-01-01

    Fatty acid content of selected seed oils from world-wide edible fruits, Ceratonia ciliqua (carob) from Caesalpiniaceae family, Diospyros kaki (persimmon) from Ebenaceae family, Zizyphus jujuba (jujube) from Rhamnaceae family, and Persea gratissima (avocado pear) from Lauraceae family, were determined by capillary gas chromatography- mass spectrometry (GC-MS) to find new natural sources for essential fatty acids. Among the seed oils analyzed, Ceratonia ciliqua has been found to have the highest essential fatty acid content.

  14. Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation

    International Nuclear Information System (INIS)

    Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [125I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [125I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [125I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [125I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [125I]insulin receptor binding was noted at all time points in the molecular layer of the dentate

  15. cis-Cinnamic acid selective suppressors distinct from auxin inhibitors.

    Science.gov (United States)

    Okuda, Katsuhiro; Nishikawa, Keisuke; Fukuda, Hiroshi; Fujii, Yoshiharu; Shindo, Mitsuru

    2014-01-01

    The activity of cis-cinnamic acid (cis-CA), one of the allelochemicals, in plants is very similar to that of indole-3-acetic acid (IAA), a natural auxin, and thus cis-CA has long been believed to be an analog of auxin. We have reported some structure-activity relationships studies by synthesizing over 250 cis-CA derivatives and estimating their inhibitory activities on root growth inhibition in lettuce. In this study, the compounds that showed low- or no-activity on root growth inhibition were recruited as candidates suppressors against cis-CA and/or auxin and tested for their activity. In the presence of cis-CA, lettuce root growth was inhibited; however, the addition of some cis-CA derivatives restored control-level root growth. Four compounds, (Z)-3-(4-isopropylphenyl)acrylic acid, (Z)-3-(3-butoxyphenyl)acrylic acid, (Z)-3-[3-(pentyloxy)phenyl]acrylic acid, and (Z)-3-(naphthalen-1-yl)acrylic acid were selected as candidates for a cis-CA selective suppressor they allowed the recovery of root growth from inhibition by cis-CA treatment without any effects on the IAA-induced effect or elongating activity by themselves. Three candidates significantly ameliorated the root shortening by the potent inhibitor derived from cis-CA. In brief, we have found some cis-CA selective suppressors which have never been reported from inactive cis-CA derivatives for root growth inhibition. cis-CA selective suppressors will play an important role in elucidating the mechanism of plant growth regulation. PMID:24881667

  16. In vitro selection of functional nucleic acids

    Science.gov (United States)

    Wilson, D. S.; Szostak, J. W.

    1999-01-01

    In vitro selection allows rare functional RNA or DNA molecules to be isolated from pools of over 10(15) different sequences. This approach has been used to identify RNA and DNA ligands for numerous small molecules, and recent three-dimensional structure solutions have revealed the basis for ligand recognition in several cases. By selecting high-affinity and -specificity nucleic acid ligands for proteins, promising new therapeutic and diagnostic reagents have been identified. Selection experiments have also been carried out to identify ribozymes that catalyze a variety of chemical transformations, including RNA cleavage, ligation, and synthesis, as well as alkylation and acyl-transfer reactions and N-glycosidic and peptide bond formation. The existence of such RNA enzymes supports the notion that ribozymes could have directed a primitive metabolism before the evolution of protein synthesis. New in vitro protein selection techniques should allow for a direct comparison of the frequency of ligand binding and catalytic structures in pools of random sequence polynucleotides versus polypeptides.

  17. Selection of lactic acid bacteria able to ferment inulin hydrolysates

    OpenAIRE

    Octavian BASTON; Oana Emilia CONSTANTIN

    2012-01-01

    Eight homofermentative lactic acid bacteria isolates were tested for lactic acid production using chicory and Jerusalem artichoke hydrolysate as substrate. The pH, lactic acid yield and productivity were used to select the best homolactic bacteria for lactic acid production. The selected strains produced lactic acid at maximum yield after 24 hours of fermentation and the productivity was greater at 24 hours of fermentation. From all studied strains, Lb1 and Lb2 showed the best results regardi...

  18. Tranexamic acid-induced fixed drug eruption

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    Natsuko Matsumura

    2015-01-01

    Full Text Available A 33-year-old male showed multiple pigmented patches on his trunk and extremities after he took tranexamic acid for common cold. He stated that similar eruptions appeared when he was treated with tranexamic acid for influenza 10 months before. Patch test showed positive results at 48 h and 72 h by 1% and 10% tranexamic acid at the lesional skin only. To our knowledge, nine cases of fixed drug eruption induced by tranexamic acid have been reported in Japan. Tranexamic acid is a safe drug and frequently used because of its anti-fibrinolytic and anti-inflammatory effects, but caution of inducing fixed drug eruption should be necessary.

  19. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

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    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  20. Selective enhancement of topologically induced interface states

    CERN Document Server

    Poli, C; Kuhl, U; Mortessagne, F; Schomerus, H

    2014-01-01

    An attractive mechanism to induce robust spatially confined states utilizes interfaces between regions with topologically distinct gapped band structures. For electromagnetic waves, this mechanism can be realized in two dimensions by breaking symmetries in analogy to the quantum Hall effect or by employing analogies to the quantum spin Hall effect, while in one dimension it can be obtained by geometric lattice modulation. Induced by the presence of the interface, a topologically protected, exponentially confined state appears in the middle of the band gap. The intrinsic robustness of such states raises the question whether their properties can be controlled and modified independently of the other states in the system. Here, we draw on concepts from passive non-hermitian parity-time (PT)-symmetry to demonstrate the selective control and enhancement of a topologically induced state in a one-dimensional microwave set-up. In particular, we show that the state can be isolated from losses that affect all other mode...

  1. Enantiomer-specific selection of amino acids.

    Science.gov (United States)

    Ren, Xueying; Tellez, Luis A; de Araujo, Ivan E

    2013-12-01

    Dietary intake of L-amino acids impacts on several physiological functions, including the control of gastrointestinal motility, pancreatic secretion, and appetite. However, the biological mechanisms regulating behavioral predilections for certain amino acid types remain poorly understood. We tested the hypothesis that, in mice, the potency with which a given glucogenic amino acid increases glucose utilization reflects its rewarding properties. We have found that: (1) during long-, but not short-, term preference tests, L-alanine and L-serine were preferred over their D-enantiomer counterparts, while no such effect was observed for L-threonine vs. D-threonine; (2) these behavioral patterns were closely associated with the ability of L-amino acids to promote increases in respiratory exchange ratios such that those, and only those, L-amino acids able to promote increases in respiratory exchange ratios were preferred over their D-isomers; (3) these behavioral preferences were independent of gustatory influences, since taste-deficient Trpm5 knockout mice displayed ingestive responses very similar to those of their wild-type counterparts. We conclude that the ability to promote increases in respiratory exchange ratios enhances the reward value of nutritionally relevant amino acids and suggest a mechanistic link between substrate utilization and amino acid preferences.

  2. Mast cell degranulation induced by chlorogenic acid

    OpenAIRE

    Huang, Fang-hua; Zhang, Xin-yue; Zhang, Lu-Yong; Li, Qin; Ni, Bin; Zheng, Xiao-liang; CHEN, AI-JUN

    2010-01-01

    Aim: To investigate the mechanism of chlorogenic acid (CA)-induced anaphylactoid reactions. Methods: Degranulation of peritoneal mast cells was assayed by using alcian blue staining in guinea pigs, and the degranulation index (DI) was calculated. CA-induced degranulation of RBL-2H3 cells was also observed and assayed using light microscopy, transmission electron microscopy, flow cytometry, and β-hexosaminidase release. Results: CA 0.2, 1.0, and 5.0 mmol/L was able to promote degranulation of ...

  3. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors ...

  4. Enantiomeric Selective Adsorption of Amino Acid by Polysaccharide Composite Materials

    OpenAIRE

    Duri, Simon; Tran, Chieu D.

    2014-01-01

    A composite containing cellulose (CEL) and chitosan (CS) synthesized by a simple and recyclable method by using butylmethylimmidazolium chloride, an ionic liquid, was found to exhibit remarkable enantiomeric selectivity toward adsorption of amino acids. 100%CS shows the highest adsorption capacity and enantiomeric selectivity. A racemic amino acid can be enantiomerically resolved by 100%CS in about 96–120 hrs. Interestingly, adsorption by 50:50 CEL:CS is more similar to that by 100%CS than to...

  5. Selective Conversion of Biorefinery Lignin into Dicarboxylic Acids

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Ruoshui; Guo, Mond; Zhang, Xiao

    2014-02-01

    The emerging biomass-to-biofuel conversion industry has created an urgent need for identifying new applications for biorefinery lignin. This paper demonstrates a new route to producing dicarboxylic acids from biorefinery lignin through chalcopyrite-catalyzed oxidation in a highly selective process. Up to 95 % selectivity towards stable dicarboxylic acids was obtained for several types of biorefinery lignin and model compounds under mild, environmentally friendly reaction conditions. The findings from this study paved a new avenue to biorefinery lignin conversions and applications.

  6. Selective deoxygenation of stearic acid via an anhydride pathway

    NARCIS (Netherlands)

    Hollak, S.A.W.; Bitter, W.; Haveren, van J.; Es, van D.S.

    2012-01-01

    Stearic anhydride is proposed as reactive intermediate in the hydrogen free decarbonylation and ketonization of stearic acid over Pd/Al2O3 at 523 K. This information is crucial towards developing of a selective low temperature decarbonylation process of fatty acids towards olefins.

  7. Selection of lactic acid bacteria able to ferment inulin hydrolysates

    Directory of Open Access Journals (Sweden)

    Octavian BASTON

    2012-12-01

    Full Text Available Eight homofermentative lactic acid bacteria isolates were tested for lactic acid production using chicory and Jerusalem artichoke hydrolysate as substrate. The pH, lactic acid yield and productivity were used to select the best homolactic bacteria for lactic acid production. The selected strains produced lactic acid at maximum yield after 24 hours of fermentation and the productivity was greater at 24 hours of fermentation. From all studied strains, Lb1 and Lb2 showed the best results regarding lactic acid yields andproductivity. After 48 hours of chicory and Jerusalem artichhoke hydrolysates fermentation, from all the studied strains, Lb2 produced the highest lactic acid yield (0.97%. Lb2 produced after 48 hours of fermentation the lowest pH value of 3.45±0.01. Lb2 showed greater lactic acid productivity compared to the other studied lactic acid bacteria, the highest values, 0.13 g·L-1·h-1fromJerusalem artichoke hydrolysate and 0.11g·L-1·h-1 from chicory hydrolysate, being produced after 24 hours of fermentation.

  8. Aromatic amino acids in high selectivity bismuth(III) recognition.

    Science.gov (United States)

    Ghatak, Sumanta Kumar; Dey, Debarati; Sen, Souvik; Sen, Kamalika

    2013-04-21

    The three aromatic amino acids, tyrosine, tryptophan and phenylalanine, play different physiological roles in life processes. Metal ions capable of binding these amino acids may aid in the reduction of effective concentration of these amino acids in any physiological system. Here we have studied the efficacy of some heavy metals for their complexation with these three amino acids. Bismuth has been found to bind selectively with these aromatic amino acids and this was confirmed using spectrofluorimetric, spectrophotometric and cyclic voltammetric studies. The series of heavy metals has been chosen because each of these metals remains associated with the others at very low concentration levels and Bi(III) is the least toxic amongst the other elements. So, selective recognition for Bi(III) would also mean no response for the other heavy elements if contaminants are present even at low concentration levels. The affinity towards these amino acids has been found to be in the order tryptophan phenylalanine amino acids have been calculated using Benesi-Hildebrand equations and the corresponding free energy change has also been calculated. The values of the association constants obtained from BH equations using absorbance values corroborate with the Stern-Volmer constants obtained from fluorimetric studies. The evidence for complexation is also supported by the results of cyclic voltammetry.

  9. Transcript and metabolite alterations increase ganoderic acid content in Ganoderma lucidum using acetic acid as an inducer.

    Science.gov (United States)

    Ren, Ang; Li, Xiong-Biao; Miao, Zhi-Gang; Shi, Liang; Jaing, Ai-Liang; Zhao, Ming-Wen

    2014-12-01

    Acetic acid at 5-8 mM increased ganoderic acid (GA) accumulation in Ganoderma lucidum. After optimization by the response surface methodology, the GA content reached 5.5/100 mg dry weight, an increase of 105% compared with the control. The intermediate metabolites of GA biosynthesis, lanosterol and squalene also increased to 47 and 15.8 μg/g dry weight, respectively, in response to acetic acid. Acetic acid significantly induced transcription levels of sqs, lano, hmgs and cyp51 in the GA biosynthesis pathway. An acetic acid-unregulated acetyl coenzyme A synthase (acs) gene was selected from ten candidate homologous acs genes. The results indicate that acetic acid alters the expression of genes related to acetic acid assimilation and increases GA biosynthesis and the metabolic levels of lanosterol, squalene and GA-a, thereby resulting in GA accumulation. PMID:25216642

  10. Food-grade Selection Markers in Lactic Acid Bacteria

    OpenAIRE

    Song He; Fanghong Gong; Ya'nan Guo; Dechun Zhang.

    2012-01-01

    Lactic acid bacteria (LAB) are generally regarded as safe (GRAS) microorganisms and widely used in industry and medicine. We are trying to add additional properties to them by gene engineering. However, the genetically modified bacteria are not acceptable to use in food and medicine due to the presence of antibiotic resistance genes in plasmids. Thus, it is necessary to develop food-grade selection markers. Food-grade markers can be divided into three classes based on their selected character...

  11. Synthesis and transdermal properties of acetylsalicylic acid and selected esters.

    Science.gov (United States)

    Gerber, Minja; Breytenbach, Jaco C; Hadgraft, Jonathan; du Plessis, Jeanetta

    2006-03-01

    The primary aim of this study was to determine the transdermal penetration of acetylsalicylic acid and some of its derivatives, to establish a correlation, if any, with selected physicochemical properties and to determine if transdermal application of acetylsalicylic acid and its derivatives will give therapeutic drug concentrations with respect to transdermal flux. Ten derivatives of acetylsalicylic acid were prepared by esterification of acetylsalicyloyl chloride with ten different alcohols. The experimental aqueous solubility, logD and transdermal flux values were determined for acetylsalicylic acid and its derivatives at pH 4.5. In vitro penetration was measured through excised female human abdominal skin in diffusion cells. The experimental aqueous solubility of acetylsalicylic acid (6.56 mg/ml) was higher than that of the synthesised acetylsalicylate derivatives (ranging from 1.76 x 10(-3) to 3.32 mg/ml), and the logD of acetylsalicylic acid (-0.85) was lower than that of its derivatives (ranging from -0.25 to 1.95). There was thus an inverse correlation between the aqueous solubility data and the logD values. The experimental transdermal flux of acetylsalicylic acid (263.83 nmol/cm(2)h) was much higher than that of its derivatives (ranging from 0.12 to 136.02 nmol/cm(2)h).

  12. Chromatographic selectivity study of 4-fluorophenylacetic acid positional isomers separation.

    Science.gov (United States)

    Chasse, Tyson; Wenslow, Robert; Bereznitski, Yuri

    2007-07-13

    Unique properties of the fluorine atom stimulate widespread use and development of new organofluorine compounds in agrochemistry, biotechnology and pharmacology applications. However, relatively few synthetic methods exhibit a high degree of fluorination selectivity, which ultimately results in the presence of structurally related fluorinated isomers in the synthetic product. This outcome is undesirable from a pharmaceutical perspective as positional isomers possess different reactivity, biological activity and toxicity as compared to the desired product. It is advantageous to control positional isomers in the early stages of the synthetic process, as rejection and analysis of these isomers will likely become more difficult in later stages. The current work reports the development of a chromatographic analysis of 2- and 3-fluorophenylacetic acid positional isomer impurities in 4-fluorophenylacetic acid (4-FPAA), a building block in the synthesis of an active pharmaceutical ingredient. The method is employed as a part of a Quality by Design Approach to control purity of the starting material in order to eliminate the presence of undesirable positional isomers in the final drug substance. During method development, a wide range of chromatographic conditions and structurally related positional isomer probe molecules were exploited in an effort to gain insight into the specifics of the separation mechanism. For the systems studied it was shown that the choice of organic modifier played a key role in achieving acceptable separation. Further studies encompassed investigation of temperature influence on retention and selectivity of the FPAA isomers separation. Thermodynamic analysis of these data showed that the selectivity of the 2- and 4- fluorophenylacetic acids separation was dominated by an enthalpic process, while the selectivity of the 4- and 3-fluorophenylacetic acids separation was exclusively entropy driven (Delta(DeltaH degrees approximately 0). Studies of

  13. Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria.

    Science.gov (United States)

    Salvi, Mauro; Fiore, Cristina; Armanini, Decio; Toninello, Antonio

    2003-12-15

    Glycyrrhetinic acid, a hydrolysis product of one of the main constituents of licorice, the triterpene glycoside of glycyrrhizic acid, when added to rat liver mitochondria at micromolar concentrations induces swelling, loss of membrane potential, pyridine nucleotide oxidation, and release of cytochrome c and apoptosis inducing factor. These changes are Ca(2+) dependent and are prevented by cyclosporin A, bongkrekic acid, and N-ethylmaleimide. All these observations indicate that glycyrrhetinic acid is a potent inducer of mitochondrial permeability transition and can trigger the pro-apoptotic pathway. PMID:14637195

  14. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Directory of Open Access Journals (Sweden)

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

  15. Adsorption selectivity of salicylic acid and 5-sulfosalicylic acid onto hypercrosslinked polymeric adsorbents

    Institute of Scientific and Technical Information of China (English)

    LIU Fuqiang; XIA Mingfang; FEI Zhenghao; CHEN Jinlong; LI Aimin

    2007-01-01

    Both bottle-point and column-feeding experiments involving different solutes and sorbents were carried out to investigate the adsorption selectivity and separation performance of salicylic acid and 5-sulfosalicylic acid.Their adsorption isotherms onto such hypercrosslinked polymeric adsorbents as NDA-100 and NDA-99 could be well described by the Freundlich equations whose characteristics describe extrathermic and favorable adsorption processes.The adsorption towards NDA-100 mainly depended on the π-π interaction,while that towards NDA-99 was extremely influenced by the static-electric interaction.Additionally,the adsorptive capacity of salicylic acid on NDA-99 decreased while it increased on NDA-100 with the presence of 5-sulfosalicylic acid in the adsorptive environment as the competitive component.Comparatively,the adsorption capacity of 5-sulfosalicylic acid decreased on both resins with salicylic acid as the competitive component.In fact,the difference in the interaction between adsorbent and adsorbate resulted in the straight antagonism on the effective adsorption sites on the adsorbent.In conclusion,the adsorption selectivity of salicylic acid onto NDA-100 was obviously larger than that onto NDA-99 with the existence of 5-sulfosalicylic acid in the adsorptive environment.A satisfactory separation and recovery of tested solutes in aqueous phase could be foreseeably achieved by the sequencing adsorption technique involving NDA-100 as well as NDA-99.

  16. Influence of selected factors on induced syneresis

    Directory of Open Access Journals (Sweden)

    Jovanović Snežana T.

    2004-01-01

    Full Text Available Syneresis is the process of whey separation induced by gel contraction resulting in rearranging or restructuring of casein matrix formed during enzymatic coagulation. Numerous factors can influence the process of syneresis. The influences of pH, calcium concentration, temperature of coagulation of milk and applied heat treatment on the syneresis induced by different intensity of centrifugal force have been investigated. Coagulated samples were centrifuged at 1000, 2000 and 3000 rpm for 5 min, respectively. Reconstituted skim milk powder (control sample and reconstituted non-fat milk heat treated at 87ºC/10 min (experimental sample are coagulated at temperatures of 30ºC and 35ºC, at pH value of 5.8 and 6.2, and with the addition of 100, 200 and 400 mg/l of CaCl2, respectively. Centrifugation at 1000 rpm of both control and experimental samples didn’t recover any sera, regardless of the applied coagulation conditions. This indicates that the intensity of centrifugal force wasn’t strong enough to disrupt gel structure and cause syneresis. When the intensity of centrifugal force was increased up to 2000 rpm, the syneresis was induced, but the degree of syneresis depended on the applied factors of coagulation, primary on the applied heat treatments and temperature of coagulation. The amount of added CaCl2 didn’t have a significant influence on the induced syneresis at 2000 rpm. The induced syneresis was very significant for both control and experimental samples when the intensity of centrifugal force of 3000 rpm was applied. It was also noted that curd produced from heat treated milk in which milk protein coaggregates were formed, released less sera regardless of the applied coagulation factors.

  17. Oleic acid-embedded nanoliposome as a selective tumoricidal agent.

    Science.gov (United States)

    Jung, Sujin; Lee, Sangah; Lee, Hyejin; Yoon, Jaejin; Lee, E K

    2016-10-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cell), a molecular complex of human α-lactalbumin and oleic acid, is known to have selective cytotoxic activity against certain types of tumors. This cytotoxicity is known to stem from water-insoluble oleic acid. In this study, we manufactured an alternative complex using liposome as an oleic acid delivery vesicle. We named this nanolipoplex LIMLET (LIposome Made LEthal to Tumor cell). The LIMLET vesicle contained approximately 90,200 oleic acid molecules inserted into its lipophilic phospholipid bilayer and had a nominal mean diameter of 127nm. Using a WST-1 assay, its cytotoxicity against two cancer cell lines, MDA-MB-231 (human breast cancer) and A549 (human lung cancer), were tested. The results were compared with that of a normal cell line, Vero (from monkey kidney). We found that (1) LIMLET showed distinctive cytotoxicity against A549 and MDA-MB-231 cells, whereas bare liposomes (containing no oleic acid) had no toxicity, even at high concentrations, and (2) LIMLET demonstrated selective, concentration-dependent toxicity against the cancer cells: the LD50 values of MDA-MB-231 and A549 cells were 1.3 and 2.2nM LIMLET, respectively, whereas the LD50 of Vero was 5.7nM. The strength of the tumoricidal effect appeared to stem from the number of oleic acid molecules present. Our result suggests that LIMLET, like HAMLET, is an interesting nanolipoplex that can potentially be developed into tumor treatments.

  18. Oleic acid-embedded nanoliposome as a selective tumoricidal agent.

    Science.gov (United States)

    Jung, Sujin; Lee, Sangah; Lee, Hyejin; Yoon, Jaejin; Lee, E K

    2016-10-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cell), a molecular complex of human α-lactalbumin and oleic acid, is known to have selective cytotoxic activity against certain types of tumors. This cytotoxicity is known to stem from water-insoluble oleic acid. In this study, we manufactured an alternative complex using liposome as an oleic acid delivery vesicle. We named this nanolipoplex LIMLET (LIposome Made LEthal to Tumor cell). The LIMLET vesicle contained approximately 90,200 oleic acid molecules inserted into its lipophilic phospholipid bilayer and had a nominal mean diameter of 127nm. Using a WST-1 assay, its cytotoxicity against two cancer cell lines, MDA-MB-231 (human breast cancer) and A549 (human lung cancer), were tested. The results were compared with that of a normal cell line, Vero (from monkey kidney). We found that (1) LIMLET showed distinctive cytotoxicity against A549 and MDA-MB-231 cells, whereas bare liposomes (containing no oleic acid) had no toxicity, even at high concentrations, and (2) LIMLET demonstrated selective, concentration-dependent toxicity against the cancer cells: the LD50 values of MDA-MB-231 and A549 cells were 1.3 and 2.2nM LIMLET, respectively, whereas the LD50 of Vero was 5.7nM. The strength of the tumoricidal effect appeared to stem from the number of oleic acid molecules present. Our result suggests that LIMLET, like HAMLET, is an interesting nanolipoplex that can potentially be developed into tumor treatments. PMID:27424089

  19. Selective cellular acidification and toxicity of weak organic acids in an acidic microenvironment.

    Science.gov (United States)

    Karuri, A R; Dobrowsky, E; Tannock, I F

    1993-12-01

    The mean extracellular pH (pHe) within solid tumours has been found to be lower than in normal tissues. Agents which cause intracellular acidification at low pHe might have selective toxicity towards cells in tumours. Weak acids (or their anions) with pKa values in the range of 4-6 have a higher proportion of molecules in the uncharged form at low pHe and can diffuse more rapidly into cells. The effects of organic acids including succinate, monomethyl succinate and malonate to acidify cells have been evaluated under conditions of different pHe in the acidic range. These weak acids caused intracellular acidification of murine EMT-6 and human MGH-U1 cells in a concentration and pHe dependent fashion. At concentrations of 10 mM and above, these acids also caused in vitro cytotoxicity to these cells at low pHe (< 6.5). The rate and extent of cellular acidification caused by these weak acids, and their cytotoxicity at low pHe, were enhanced by exposure to amiloride and 5-(N-ethyl-N-isopropyl)amiloride (EIPA), agents which inhibit Na+/H+ exchange, and hence the regulation of intracellular pH. Acid dependent cytotoxicity was also investigated in a murine solid tumour using the endpoints of growth delay and colony formation in vitro following treatment in vivo. Agents were tested alone or with 15 Gy X-rays to select a population of hypoxic (and presumably acidic) cells. Achievable serum concentrations of succinate were about 1 mM and no antitumour activity of succinate was detected when used in this way. It is concluded that weak acids are selectively taken up into cells, and can cause selective cellular acidification and toxicity, at low pHe in culture. Weak acids that are normal cellular metabolites are not toxic in vivo, but weak acids carrying cytotoxic groups offer the potential for selective uptake and toxicity under the conditions of low pHe that exist in many solid tumours.

  20. Comparison of D-gluconic acid production in selected strains of acetic acid bacteria.

    Science.gov (United States)

    Sainz, F; Navarro, D; Mateo, E; Torija, M J; Mas, A

    2016-04-01

    The oxidative metabolism of acetic acid bacteria (AAB) can be exploited for the production of several compounds, including D-gluconic acid. The production of D-gluconic acid in fermented beverages could be useful for the development of new products without glucose. In the present study, we analyzed nineteen strains belonging to eight different species of AAB to select those that could produce D-gluconic acid from D-glucose without consuming D-fructose. We tested their performance in three different media and analyzed the changes in the levels of D-glucose, D-fructose, D-gluconic acid and the derived gluconates. D-Glucose and D-fructose consumption and D-gluconic acid production were heavily dependent on the strain and the media. The most suitable strains for our purpose were Gluconobacter japonicus CECT 8443 and Gluconobacter oxydans Po5. The strawberry isolate Acetobacter malorum (CECT 7749) also produced D-gluconic acid; however, it further oxidized D-gluconic acid to keto-D-gluconates.

  1. Selective and recyclable depolymerization of cellulose to levulinic acid catalyzed by acidic ionic liquid.

    Science.gov (United States)

    Ren, Huifang; Girisuta, Buana; Zhou, Yonggui; Liu, Li

    2015-03-01

    Cellulose depolymerization to levulinic acid (LA) was catalyzed by acidic ionic liquids (ILs) selectively and recyclably under hydrothermal conditions. The effects of reaction temperature, time, water amount and cellulose intake were investigated. Dilution effect becomes more pronounced at lower cellulose intake, dramatically improving the yield of LA to 86.1%. A kinetic model has been developed based on experimental data, whereby a good fit was obtained and kinetic parameters were derived. The relationships between IL structure, polymeric structure and depolymerization efficiency were established, shedding light on the in-depth catalytic mechanism of IL, inclusive of acidity and hydrogen bonding ability. The LA product can be readily separated through extraction by methyl isobutyl ketone (MIBK) and IL can be reused over five cycles without loss of activity. This environmentally friendly methodology can be applied to selective production of LA from versatile biomass feedstocks, including cellulose and derivatives, glucose, fructose and HMF.

  2. Selective esterification of non-conjugated carboxylic acids in the presence of conjugated or aromatic carboxylic acids over active carbon supported methanesulfonic acid

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Non-conjugated carboxylic acids are selectively esterified in good yields in the presence of conjugated or aromatic carboxylic acids by stirring over active carbon supported methanesulfonic acid in di-chloromethane at room temperature.

  3. Chlorine dioxide reaction with selected amino acids in water

    International Nuclear Information System (INIS)

    Chlorine dioxide is a hypochlorite alternative disinfectant agent. In this context, we have determined the products formed in the reaction of ClO2 with selected amino acids as model compounds that can be present in natural waters. The reaction of tryptophane, histidine and tyrosine (10 ppm each) with ClO2 were studied at molar ratios ranging from 0.25 to 4 in the presence or absence of oxygen. It was found that in the absence of oxygen adding substoichiometric amounts of ClO2 creates products that are structurally similar to the starting amino acids. Through a series of cascade reactions the initial product distribution gradually evolves toward simple, small carbon chain products that are far from the starting amino acid. The reaction product distribution revealed that chlorine dioxide can attack the electron-rich aromatic moieties as well as the nitrogen atom lone electron pair. Our study is relevant to gain knowledge on the reaction mechanism of ClO2 with ubiquitous amino acids present in natural waters.

  4. Hyaluronic acid induces activation of the κ-opioid receptor.

    Directory of Open Access Journals (Sweden)

    Barbara Zavan

    Full Text Available INTRODUCTION: Nociceptive pain is one of the most common types of pain that originates from an injury involving nociceptors. Approximately 60% of the knee joint innervations are classified as nociceptive. The specific biological mechanism underlying the regulation of nociceptors is relevant for the treatment of symptoms affecting the knee joint. Intra-articular administration of exogenous hyaluronic acid (HA in patients with osteoarthritis (OA appears to be particularly effective in reducing pain and improving patient function. METHODS: We performed an in vitro study conducted in CHO cells that expressed a panel of opioid receptors and in primary rat dorsal root ganglion (DRG neurons to determine if HA induces the activation of opioid peptide receptors (OPr using both aequorin and the fluorescent dye Fura-2/AM. RESULTS: Selective agonists and antagonists for each OPr expressed on CHO cells were used to test the efficacy of our in vitro model followed by stimulation with HA. The results showed that HA induces stimulatory effects on the κ receptor (KOP. These effects of HA were also confirmed in rat DRG neurons, which express endogenously the OPr. CONCLUSIONS: HA activates the KOP receptor in a concentration dependent manner, with a pEC(50 value of 7.57.

  5. Effects of phenylalaninol on centrally induced gastric acid secretion.

    Science.gov (United States)

    Hashizume, H; Miyamae, T; Morikawa, T; Hagiwara, M

    1992-11-01

    The effects of phenylalaninol (D-isomer) on gastric acid secretion and gastric ulcer were studied in rats. The compound reduced the gastric acid secretion stimulated by intracisternal thyrotropin releasing hormone and intravenous 2-deoxy-D-glucose, but not that stimulated by subcutaneous carbachol or histamine. Phenylalaninol prevented stress- and indomethacin-induced gastric ulcers. We conclude that phenylalaninol inhibits ulcer formation mainly by central inhibition of gastric acid secretion. PMID:1477931

  6. Preparation of Glycyrrhetinic Acid Monoglucuronide by Selective Hydrolysis of Glycyrrhizic Acid via Biotransformation

    Institute of Scientific and Technical Information of China (English)

    LU Li; MA Bai-ping; ZHAO Yang; YU He-shui; HUANG Hong-zhi; KANG Li-ping; CAO Man; CUI Jiang-ming; YU Li-yan; SONG Xin-bo

    2012-01-01

    Objective To search for the microorganisms which have the high selectivity of hydrolyzing glycyrrhizic acid(GL)into 18β-glycyrrhetinic acid-3-O-β-D-glucuronide(GAMG)without glycyrrhetinic acid(GA)byproduct.Methods GL was biotransformed by Aspergillus sp.,the products were separated by chromatography on reverse phase C18 column and semi-preparative HPLC,and their structures were elucidated on the basis of HR-ESI-MS,1D NMR(1H-NMR,13C-NMR,and NOESY)and 2D NMR(1H-1H COSY,HSQC,and HMBC)spectral analyses.Results Aspergillus sp.could partially hydrolyze GL into GAMG(3),along with two minor byproducts,3-O-β-D-glucurono-pyranosyl-18β-liquiritic acid(1)and 3-O-β-D-glucuronopyranosyl-24-hydroxy-18β-glycyrrhetinic acid(2).Conclusion Aspergillus sp.has the high selectivity of hydrolyzing GL into GAMG without GA byproduct and the yield of GAMG is about 60%.The complete assignments of 1H-NMR and 13C-NMR data for compounds 1 and 2 are reported for the first time.

  7. Citric acid production by selected mutants of Aspergillus niger from cane molasses.

    Science.gov (United States)

    Ikram-Ul, Haq; Ali, Sikander; Qadeer, M A; Iqbal, Javed

    2004-06-01

    The present investigation deals with citric acid production by some selected mutant strains of Aspergillus niger from cane molasses in 250 ml Erlenmeyer flasks. For this purpose, a conidial suspension of A. niger GCB-75, which produced 31.1 g/l citric acid from 15% (w/v) molasses sugar, was subjected to UV-induced mutagenesis. Among the 3 variants, GCM-45 was found to be a better producer of citric acid (50.0 +/- 2a) and it was further improved by chemical mutagenesis using N-methyl, N-nitro-N-nitroso-guanidine (MNNG). Out of 3,2-deoxy-D-glucose resistant variants, GCMC-7 was selected as the best mutant, which produced 96.1 +/- 1.5 g/l citric acid 168 h after fermentation of potassium ferrocyanide and H2SO4 pre-treated blackstrap molasses in Vogel's medium. On the basis of kinetic parameters such as volumetric substrate uptake rate (Qs), and specific substrate uptake rate (qs), the volumetric productivity, theoretical yield and specific product formation rate, it was observed that the mutants were faster growing organisms and produced more citric acid. The mutant GCMC-7 has greater commercial potential than the parental strain with regard to citrate synthase activity. The addition of 2.0 x 10(-5) M MgSO4 x 5H2O into the fermentation medium reduced the Fe2+ ion concentration by counter-acting its deleterious effect on mycelial growth. The magnesium ions also induced a loose-pelleted form of growth (0.6 mm, diameter), reduced the biomass concentration (12.5 g/l) and increased the volumetric productivity of citric acid monohydrate (113.6 +/- 5 g/l).

  8. Poly(acrylic acid) to induce competitive crystallization of a theophylline/oxalic acid cocrystal and a theophylline polymorph

    Science.gov (United States)

    Jang, Jisun; Kim, Il Won

    2016-01-01

    Polymeric additives to induce competitive crystallization of pharmaceutical compounds were explored. A cocrystal of theophylline and oxalic acid was used as a model system, and poly(acrylic acid), poly(caprolactone), and poly(ethylene glycol) were the additives. The cocrystal formation was selectively hindered with addition of poly(acrylic acid). First the size of the cocrystals were reduced, and eventually the cocrystallization was inhibited to generate neat theophylline crystals. The theophylline crystals were of a distinctively different crystal structure from known polymorphs, based on powder X-ray diffraction. They were also obtained in nanoscale size, when millimeter-scale crystals formed without poly(acrylic acid). Polymeric additives that could form specific interactions with crystallizing compounds seem to be useful tools for the phase and size control of pharmaceutical crystals.

  9. Perflurooctanoic Acid Induces Developmental Cardiotoxicity in Chicken Embryos and Hatchlings

    Science.gov (United States)

    Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxi...

  10. Metal induced amino acid adsorption on nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Chia M., E-mail: abinitio@dragon.nchu.edu.t [Research Center for the Remediation of Soil and Ground Water Pollution, Department of Soil and Environmental Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Jalbout, Abraham F. [Departamento de Investigacion en Fisica, Universidad de Sonora, Hermosillo, Sonora C.P., 83000 Mexico (Mexico)

    2010-02-01

    In this work we detail the mechanism by which alkali metal encapsulation inside an armchair (9,9) single walled carbon nanotube (SWNT) can affect external amino acid interactions. Based on our analysis, several configurations revealed that the physical properties of the SWNT systems are modified by using an internally situated Li atom. Density-functional theory calculations reveal that the most favorable interactions of the SWNT system is with tryptophan, threonine and proline that can be directly correlated to the backbone geometry of the amino acid species.

  11. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption

    Science.gov (United States)

    Xie, Guoxiang; Zhong, Wei; Li, Houkai; Li, Qiong; Qiu, Yunping; Zheng, Xiaojiao; Chen, Huiyuan; Zhao, Xueqing; Zhang, Shucha; Zhou, Zhanxiang; Zeisel, Steven H.; Jia, Wei

    2013-01-01

    Our understanding of the bile acid metabolism is limited by the fact that previous analyses have primarily focused on a selected few circulating bile acids; the bile acid profiles of the liver and gastrointestinal tract pools are rarely investigated. Here, we determined how chronic ethanol consumption altered the bile acids in multiple body compartments (liver, gastrointestinal tract, and serum) of rats. Rats were fed a modified Lieber-DeCarli liquid diet with 38% of calories as ethanol (the amount equivalent of 4–5 drinks in humans). While conjugated bile acids predominated in the liver (98.3%), duodenum (97.8%), and ileum (89.7%), unconjugated bile acids comprised the largest proportion of measured bile acids in serum (81.2%), the cecum (97.7%), and the rectum (97.5%). In particular, taurine-conjugated bile acids were significantly decreased in the liver and gastrointestinal tract of ethanol-treated rats, while unconjugated and glycine-conjugated species increased. Ethanol consumption caused increased expression of genes involved in bile acid biosynthesis, efflux transport, and reduced expression of genes regulating bile acid influx transport in the liver. These results provide an improved understanding of the systemic modulations of bile acid metabolism in mammals through the gut-liver axis.—Xie, G., Zhong, W., Li, H., Li, Q., Qiu, Y., Zheng, X., Chen, H., Zhao, X., Zhang, S., Zhou, Z., Zeisel, S. H., Jia, W. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption. PMID:23709616

  12. Cadmium Induces Retinoic Acid Signaling by Regulating Retinoic Acid Metabolic Gene Expression*

    OpenAIRE

    Cui, Yuxia; Freedman, Jonathan H.

    2009-01-01

    The transition metal cadmium is an environmental teratogen. In addition, cadmium and retinoic acid can act synergistically to induce forelimb malformations. The molecular mechanism underlying the teratogenicity of cadmium and the synergistic effect with retinoic acid has not been addressed. An evolutionarily conserved gene, β,β-carotene 15,15′-monooxygenase (BCMO), which is involved in retinoic acid biosynthesis, was studied in both Caenorhabditis elegans and murine Hepa 1–6 cells. In C. eleg...

  13. Quantum coherence generated by interference-induced state selectiveness

    OpenAIRE

    Garreau, Jean Claude

    2001-01-01

    The relations between quantum coherence and quantum interference are discussed. A general method for generation of quantum coherence through interference-induced state selection is introduced and then applied to `simple' atomic systems under two-photon transitions, with applications in quantum optics and laser cooling.

  14. Stress-induced biosynthesis of dicaffeoylquinic acids in globe artichoke.

    Science.gov (United States)

    Moglia, Andrea; Lanteri, Sergio; Comino, Cinzia; Acquadro, Alberto; de Vos, Ric; Beekwilder, Jules

    2008-09-24

    Leaf extracts from globe artichoke ( Cynara cardunculus L. var. scolymus) have been widely used in medicine as hepatoprotectant and choleretic agents. Globe artichoke leaves represent a natural source of phenolic acids with dicaffeoylquinic acids, such as cynarin (1,3-dicaffeoylquinic acid), along with its biosynthetic precursor chlorogenic acid (5-caffeoylquinic acid) as the most abundant molecules. This paper reports the development of an experimental system to induce caffeoylquinic acids. This system may serve to study the regulation of the biosynthesis of (poly)phenolic compounds in globe artichoke and the genetic basis of this metabolic regulation. By means of HPLC-PDA and accurate mass LC-QTOF MS and MS/MS analyses, the major phenolic compounds in globe artichoke leaves were identified: four isomers of dicaffeoylquinic acid, three isomers of caffeoylquinic acid, and the flavone luteolin 7-glucoside. Next, plant material was identified in which the concentration of phenolic compounds was comparable in the absence of particular treatments, with the aim to use this material to test the effect of stress application on the regulation of biosynthesis of caffeoylquinic acids. Using this material, the effect of UV-C, methyl jasmonate, and salicylic acid treatments on (poly)phenolic compounds was tested in different globe artichoke genotypes. UV-C exposure consistently increased the levels of dicaffeoylquinic acids in all genotypes, whereas the effect on compounds from the same biosynthetic pathway, for example, chlorogenic acid and luteolin-7-glucoside, was much less pronounced and was not statistically significant. No effect of methyl jasmonate or salicylic acid was found. Time-response experiments indicated that the level of dicaffeoylquinic acids reached a maximum at 24 h after UV radiation. On the basis of these results a role of dicaffeoylquinic acids in UV protection in globe artichoke is hypothesized. PMID:18710252

  15. Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures.

    Science.gov (United States)

    García-Heredia, José M; Hervás, Manuel; De la Rosa, Miguel A; Navarro, José A

    2008-06-01

    Acetylsalicylic acid (ASA), a derivative from the plant hormone salicylic acid (SA), is a commonly used drug that has a dual role in animal organisms as an anti-inflammatory and anticancer agent. It acts as an inhibitor of cyclooxygenases (COXs), which catalyze prostaglandins production. It is known that ASA serves as an apoptotic agent on cancer cells through the inhibition of the COX-2 enzyme. Here, we provide evidences that ASA also behaves as an agent inducing programmed cell death (PCD) in cell cultures of the model plant Arabidopsis thaliana, in a similar way than the well-established PCD-inducing agent H(2)O(2), although the induction of PCD by ASA requires much lower inducer concentrations. Moreover, ASA is herein shown to be a more efficient PCD-inducing agent than salicylic acid. ASA treatment of Arabidopsis cells induces typical PCD-linked morphological and biochemical changes, namely cell shrinkage, nuclear DNA degradation, loss of mitochondrial membrane potential, cytochrome c release from mitochondria and induction of caspase-like activity. However, the ASA effect can be partially reverted by jasmonic acid. Taking together, these results reveal the existence of common features in ASA-induced animal apoptosis and plant PCD, and also suggest that there are similarities between the pathways of synthesis and function of prostanoid-like lipid mediators in animal and plant organisms.

  16. Amoxicillin/clavulanic acid-induced pemphigus vulgaris: case report.

    Science.gov (United States)

    Baroni, Adone; Russo, Teresa; Faccenda, Franco; Piccolo, Vincenzo

    2012-01-01

    Drug-induced pemphigus is a well-established variety of pemphigus, presenting with clinical and histopathologic features identical to idiopathic form. Medical history plays a fundamental role in the diagnosis of drug-induced pemphigus. A large variety of drugs have been implicated in its pathogenesis and they may induce acantholysis via biochemical and/or immune mechanism. We present a case of a 69-year-old woman affected by amoxicillin/clavulanic acid-induced pemphigus and discuss its pathogenetic mechanism.

  17. Selection of mutants of capsicum annuum induced by gamma ray

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. I.; Lee, Y. B. [Korea Atomic Energy Research Institute, Taejeon (Korea, Republic of); Lee, E. K. [Chungnam National Univ., Taejeon (Korea, Republic of)

    1998-06-01

    For induction and selection of mutations of Capsicum annuum L., dry seeds of pure lines No.1 and No.2 were irradiated with gamma ray of 150Gy, 200Gy and 250Gy. Various mutants were selected such as showing early maturity, short plant height, long fruit and chlorophyll mutations. Mutation frequency of No.1 line was 3.4% in the dose of 150Gy, while the frequency of No.2 line was 2.7% in the dose of 250Gy. For selection of resistant mutant to amino acid analog, the optimum concentration of 5-methyltryptophan (5-MT) and S-(2-aminoethyl)-L-cysteine were 25 ppm and 30 ppm, respectively. Four resistant mutant lines to 5-MT were selected among 400 mutant lines.

  18. Fatty acid-induced insulin resistance

    DEFF Research Database (Denmark)

    Le Marchand-Brustel, Y; Gual, P; Grémeaux, T;

    2003-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterized by a decrease in the insulin effect on glucose transport in muscle and adipose tissue. Tyrosine phosphorylation of IRS-1 (insulin receptor...... substrate 1) and its binding to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Various studies have implicated lipids as a cause of insulin resistance in muscle. Elevated plasma fatty acid concentrations...... are associated with reduced insulin-stimulated glucose transport activity as a consequence of altered insulin signalling through PI 3-kinase. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose...

  19. Inducible gene expression system by 3-hydroxypropionic acid

    OpenAIRE

    Zhou, Shengfang; Ainala, Satish Kumar; Seol, Eunhee; Nguyen, Trinh Thi; Park, Sunghoon

    2015-01-01

    Background 3-Hydroxypropionic acid (3-HP) is an important platform chemical that boasts a variety of industrial applications. Gene expression systems inducible by 3-HP, if available, are of great utility for optimization of the pathways of 3-HP production and excretion. Results Here we report the presence of unique inducible gene expression systems in Pseudomonas denitrificans and other microorganisms. In P. denitrificans, transcription of three genes (hpdH, mmsA and hbdH-4) involved in 3-HP ...

  20. Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

    OpenAIRE

    Pavle Randjelovic; Slavimir Veljkovic; Nenad Stojiljkovic; Ljubinka Jankovic-Velickovic; Dusan Sokolovic; Milan Stoiljkovic; Ivan Ilic

    2012-01-01

    Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determi...

  1. Convective mixing induced by acid-base reactions.

    OpenAIRE

    Almarcha, Christophe; R'Honi, Yasmina; De Decker, Yannick; Trevelyan, Philip; Eckert, Kerstin; De Wit, Anne

    2011-01-01

    When two miscible solutions, each containing a reactive species, are put in contact in the gravity field, local variations in the density due to the reaction can induce convective motion and mixing. We characterize here both experimentally and theoretically such buoyancy-driven instabilities induced by the neutralization of a strong acid by a strong base in aqueous solutions. The diverse patterns obtained are shown to depend on the type of reactants used and on their relative concentrations. ...

  2. Mitochondria-dependent apoptosis of con A-activated T lymphocytes induced by asiatic acid for preventing murine fulminant hepatitis.

    Science.gov (United States)

    Guo, Wenjie; Liu, Wen; Hong, Shaocheng; Liu, Hailiang; Qian, Cheng; Shen, Yan; Wu, Xuefeng; Sun, Yang; Xu, Qiang

    2012-01-01

    Selectively facilitating apoptosis of activated T cells is essential for the clearance of pathogenic injurious cells and subsequent efficient resolution of inflammation. However, few chemicals have been reported to trigger apoptosis of activated T cells for the treatment of hepatitis without affecting quiescent T cells. In the present study, we found that asiatic acid, a natural triterpenoid, selectively triggered apoptosis of concanavalin A (Con A)-activated T cells in a mitochondria-dependent manner indicated by the disruption of the mitochondrial transmembrane potential, release of cytochrome c from mitochondria to cytosol, caspases activation, and cleavage of PARP. In addition, asiatic acid also induced the cleavage of caspase 8 and Bid and augmented Fas expression in Con A-activated T cells. However, following activation of T cells from MRL(lpr/lpr) mice with mutation of Fas demonstrated a similar susceptibility to asiatic acid-induced apoptosis compared with normal T cells, suggesting that Fas-mediated death-receptor apoptotic pathway does not mainly contribute to asiatic acid-induced cell death. Furthermore, asiatic acid significantly alleviated Con A-induced T cell-dependent fulminant hepatitis in mice, as assessed by reduced serum transaminases, pro-inflammatory cytokines, and pathologic parameters. Consistent with the in vitro results, asiatic acid also induced apoptosis of activated CD4(+) T cells in vivo. Taken together, our results demonstrated that the ability of asiatic acid to induce apoptosis of activated T cells and its potential use in the treatment of T-cell-mediated inflammatory diseases.

  3. Analysis of fatty acids in selected Macedonian edible oils

    OpenAIRE

    Ivanova, Violeta; Mitrev, Sasa; Leitner, Erich; Lankmayr, Ernst; Siegmund, Barbara; Stafilov, Trajče

    2015-01-01

    The fatty acid composition of few Macedonian edible oils, including sunflower, pumpkin seed, flax, rapeseed and sesame seeds, was determined using GC-FID analysis after derivatisation with BF3-methanolic solution. Six different types of fatty acids (FAs) were found in the oils samples. Palmitic acid (C16:0) and stearic acid (C18:0) were common in all saturates. Myristic acid (C14:0) was present in the sunflower and pumpkin seed oil. Oleic acid (C18:1), linoleic acid (C18:2) and -linolenic (C...

  4. In vitro selection of rape variants resistant to oxalic acid using haploid stem apexes

    International Nuclear Information System (INIS)

    Mutagenic treatment was made of the haploid stem apexes rape strain '9841' and '9885' with Pingyangmycin. As a result of positive selection with oxalic acid providing selection pressure, variants with significantly higher tolerance to oxalic acid than the original ones were obtained. 3 germplasm with significantly higher resistance to Sclerotinia sclerotiorum than cultivar Hu You 12 were selected from field test

  5. Near-infrared laser-induced generation of three rare conformers of glycolic acid.

    Science.gov (United States)

    Halasa, Anna; Lapinski, Leszek; Reva, Igor; Rostkowska, Hanna; Fausto, Rui; Nowak, Maciej J

    2014-07-31

    Structural transformations were induced in conformers of glycolic acid by selective excitation with monochromatic tunable near-infrared laser light. For the compound isolated in Ar matrixes, near-IR excitation led to generation of two higher-energy conformers (GAC; AAT) differing from the most stable SSC form by 180° rotation around the C-C bond. A detailed investigation of this transformation revealed that one conformer (GAC) is produced directly from the near-IR-excited most stable conformer. The other higher-energy conformer (AAT) was effectively generated only upon excitation of the primary photoproduct (GAC) with another near-IR photon. Once these higher-energy conformers of glycolic acid were generated in an Ar matrix, they could be subsequently transformed into one another upon selective near-IR excitations. Interestingly, no repopulation of the initial most stable SSC conformer occurred upon near-IR excitation of the higher-energy forms of the compound isolated in solid Ar. A dramatically different picture of near-IR-induced conformational transformations was observed for glycolic acid isolated in N2 matrixes. In this case, upon near-IR excitation, the most stable SSC form converted solely into a new conformer (SST), where the acid OH group is rotated by 180°. This conformational transformation was found to be photoreversible. Moreover, SST conformer, photoproduced in the N2 matrix, spontaneously converted to the most stable SSC form of glycolic acid, when the matrix was kept at cryogenic temperature and in the dark.

  6. Selective surface functionalization of polystyrene induced by synchrotron or UV radiation in the presence of oxygen or acrylic acid vapors; Funcionalizacao superficial seletiva de poliestireno induzida por radiacao sincrotron ou ultravioleta

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, Felipe; Kuhn, Sidiney; Weibel, Daniel E., E-mail: felipekessler@gmail.co [Universidade Federal do Rio Grande do Sul (IQ/UFRGS), Porto Alegre, RS (Brazil) Inst. de Quimica. Dept. de Fisico-Quimica

    2009-07-01

    Efficient surface functionalization of Polystyrene (PS) thin films by electromagnetic radiation in combination with a reactive gaseous atmosphere was obtained. Monochromatic synchrotron (SR) or polychromatic UV radiation were used as excitation sources. When SR was used, O{sub 2} was introduced after irradiation into the UHV chamber. UV irradiation was carried out keeping a constant flow of O{sub 2} or acrylic acid (AA) vapors during the photolysis. FTIR-ATR and XPS-NEXAFS spectra were obtained at the UFRGS and the LNLS, Campinas respectively. PS films were functionalized by monochromatic SR and then expose to O{sub 2} at specific transitions such us C 1s {yields}{sigma}{sup *}{sub C-C} excitation. It was found a high rate of COO, C=O and C-O groups at the surface (> 70%). UV-assisted treatment in the presence of AA vapors showed that an efficient polymerization process took place, such as, it was observed in previous AA low pressure RF plasma treatments. UV-assisted functionalization has the advantage of lower costs and simple set-up compared to plasma treatments. (author)

  7. Reduced Capacity for Fatty Acid Oxidation in Rats with Inherited Susceptibility to Diet-Induced Obesity

    OpenAIRE

    Ji, Hong; Friedman, Mark I.

    2007-01-01

    High-fat, energy-dense diets promote weight gain and obesity in humans and other animals, but the mechanisms underlying such diet-induced obesity remain elusive. To determine whether a reduced capacity to oxidize fat is involved in the etiology of diet-induced obesity, we examined different measures of fatty acid oxidation in rats selectively bred for susceptibility (DIO) or resistance (DR) to dietary obesity before and after they were fed a high-fat diet and became obese. DIO rats eating a l...

  8. Polystyrene nanoparticle exposure induces ion-selective pores in lipid bilayers

    Science.gov (United States)

    Negoda, Alexander; Kim, Kwang-Jin; Crandall, Edward D.; Worden, Robert M.

    2014-01-01

    A diverse range of molecular interactions can occur between engineered nanomaterials (ENM) and biomembranes, some of which could lead to toxic outcomes following human exposure to ENM. In this study, we adapted electrophysiology methods to investigate the ability of 20 nm polystyrene nanoparticles (PNP) to induce pores in model bilayer lipid membranes (BLM) that mimic biomembranes. PNP charge was varied using PNP decorated with either positive (amidine) groups or negative (carboxyl) groups, and BLM charge was varied using dioleoyl phospholipids having cationic (ethylphosphocholine), zwitterionic (phosphocholine), or anionic (phosphatidic acid) headgroups. Both positive and negative PNP induced BLM pores for all lipid compositions studied, as evidenced by current spikes and integral conductance. Stable PNP-induced pores exhibited ion selectivity, with the highest selectivity for K+ (PK/PCl ~ 8.3) observed when both the PNP and lipids were negatively charged, and the highest selectivity for Cl− (PK/PCl ~ 0.2) observed when both the PNP and lipids were positively charged. This trend is consistent with the finding that selectivity for an ion in channel proteins is imparted by oppositely charged functional groups within the channel’s filter region. The PK/PCl value was unaffected by the voltage-ramp method, the pore conductance, or the side of the BLM to which the PNP were applied. These results demonstrate for the first time that PNP can induce ion-selective pores in BLM, and that the degree of ion selectivity is influenced synergistically by the charges of both the lipid headgroups and functional groups on the PNP. PMID:23747366

  9. Selection of Lactic Acid Bacteria as Probiotic Candidate for Chicken

    Directory of Open Access Journals (Sweden)

    F. Hamida

    2015-08-01

    Full Text Available Lactic acid bacteria (LAB regarded as safe microorganisms; they can naturally live in gastrointestinal tract, so appropriately used as a probiotic for chicken. This study aimed to select six isolates of LAB (E1223, E3, E4, E5, E7, and E8 to obtain the isolates potentially as probiotic candidate for chicken. The six isolates were derived from spontaneous fermented corn obtained from Laboratory of Animal Biotechnology and Biomedical, PPSHB, Bogor Agricultural University, Indonesia. LAB isolates were tested their susceptibility to antibiotics (bambermycin, erythromycin, chloramphenicol, and tetracycline then were examined in vitro for their tolerance to gastrointestinal pH (2, 3, 4, and 7.2 and 0.5% bile salt condition, antimicrobial activity against Salmonella enteritidis and Enterococcus casseliflavus, and ability to adhere to chicken ileal cells. The results showed the isolates E5, E7, and E8 were sensitive to tetracycline and chloramphenicol, they could survive at pH 2, 3, 4, and 7.2, could survive at 0.5% bile salts, produced antimicrobial activity, and able to adhere to ileal cells (9.40±0.00 Log CFU/cm2 of E8 and were significantly (P<0.05 higher than those of control (5.30±0.14 Log CFU/cm2. In conclusion, this study showed that isolate E8 had better potential compared to isolates E5 and E7 in most in vitro assays as a probiotic candidate for chicken. E5, E7, and E8 were closely related with Pediococcus pentosaceus based on 16S rRNA gene.

  10. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  11. Iron Transformations Induced by an Acid-Tolerant Desulfosporosinus Species

    OpenAIRE

    Bertel, Doug; Peck, John; Quick, Thomas J.; Senko, John M.

    2012-01-01

    The mineralogical transformations of Fe phases induced by an acid-tolerant, Fe(III)- and sulfate-reducing bacterium, Desulfosporosinus sp. strain GBSRB4.2 were evaluated under geochemical conditions associated with acid mine drainage-impacted systems (i.e., low pH and high Fe concentrations). X-ray powder diffractometry coupled with magnetic analysis by first-order reversal curve diagrams were used to evaluate mineral phases produced by GBSRB4.2 in media containing different ratios of Fe(II) ...

  12. Laser-induced selective copper plating of polypropylene surface

    Science.gov (United States)

    Ratautas, K.; Gedvilas, M.; Stankevičiene, I.; JagminienÄ--, A.; Norkus, E.; Li Pira, N.; Sinopoli, S.; Emanuele, U.; Račiukaitis, G.

    2016-03-01

    Laser writing for selective plating of electro-conductive lines for electronics has several significant advantages, compared to conventional printed circuit board technology. Firstly, this method is faster and cheaper at the prototyping stage. Secondly, material consumption is reduced, because it works selectively. However, the biggest merit of this method is potentiality to produce moulded interconnect device, enabling to create electronics on complex 3D surfaces, thus saving space, materials and cost of production. There are two basic techniques of laser writing for selective plating on plastics: the laser-induced selective activation (LISA) and laser direct structuring (LDS). In the LISA method, pure plastics without any dopant (filler) can be used. In the LDS method, special fillers are mixed in the polymer matrix. These fillers are activated during laser writing process, and, in the next processing step, the laser modified area can be selectively plated with metals. In this work, both methods of the laser writing for the selective plating of polymers were investigated and compared. For LDS approach, new material: polypropylene with carbon-based additives was tested using picosecond and nanosecond laser pulses. Different laser processing parameters (laser pulse energy, scanning speed, the number of scans, pulse durations, wavelength and overlapping of scanned lines) were applied in order to find out the optimal regime of activation. Areal selectivity tests showed a high plating resolution. The narrowest width of a copper-plated line was less than 23 μm. Finally, our material was applied to the prototype of the electronic circuit board on a 2D surface.

  13. Lewis acid promoted ruthenium(II)-catalyzed etherifications by selective hydrogenation of carboxylic acids/esters.

    Science.gov (United States)

    Li, Yuehui; Topf, Christoph; Cui, Xinjiang; Junge, Kathrin; Beller, Matthias

    2015-04-20

    Ethers are of fundamental importance in organic chemistry and they are an integral part of valuable flavors, fragrances, and numerous bioactive compounds. In general, the reduction of esters constitutes the most straightforward preparation of ethers. Unfortunately, this transformation requires large amounts of metal hydrides. Presented herein is a bifunctional catalyst system, consisting of Ru/phosphine complex and aluminum triflate, which allows selective synthesis of ethers by hydrogenation of esters or carboxylic acids. Different lactones were reduced in good yields to the desired products. Even challenging aromatic and aliphatic esters were reduced to the desired products. Notably, the in situ formed catalyst can be reused several times without any significant loss of activity. PMID:25728921

  14. Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells

    Directory of Open Access Journals (Sweden)

    Wang Y

    2012-05-01

    Full Text Available Ye Wang,1,2,* Xiao-Yuan Zi,1,* Juan Su,1 Hong-Xia Zhang,1 Xin-Rong Zhang,3 Hai-Ying Zhu,1 Jian-Xiu Li,1 Meng Yin,3 Feng Yang,3 Yi-Ping Hu,11Department of Cell Biology, 2School of Clinical Medicine, 3Department of Pharmaceuticals, Second Military Medical University, Shanghai, People's Republic of China*Authors contributed equally.Abstract: In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy.Keywords: nanomedicine, selective cytotoxicity, apoptosis, cell cycle arrest, mitochondrion-targeted nanomaterials

  15. Selective Enrichment of Omega-3 Fatty Acids in Oils by Phospholipase A1.

    Science.gov (United States)

    Ranjan Moharana, Tushar; Byreddy, Avinesh R; Puri, Munish; Barrow, Colin; Rao, Nalam Madhusudhana

    2016-01-01

    Omega fatty acids are recognized as key nutrients for healthier ageing. Lipases are used to release ω-3 fatty acids from oils for preparing enriched ω-3 fatty acid supplements. However, use of lipases in enrichment of ω-3 fatty acids is limited due to their insufficient specificity for ω-3 fatty acids. In this study use of phospholipase A1 (PLA1), which possesses both sn-1 specific activity on phospholipids and lipase activity, was explored for hydrolysis of ω-3 fatty acids from anchovy oil. Substrate specificity of PLA1 from Thermomyces lenuginosus was initially tested with synthetic p-nitrophenyl esters along with a lipase from Bacillus subtilis (BSL), as a lipase control. Gas chromatographic characterization of the hydrolysate obtained upon treatment of anchovy oil with these enzymes indicated a selective retention of ω-3 fatty acids in the triglyceride fraction by PLA1 and not by BSL. 13C NMR spectroscopy based position analysis of fatty acids in enzyme treated and untreated samples indicated that PLA1 preferably retained ω-3 fatty acids in oil, while saturated fatty acids were hydrolysed irrespective of their position. Hydrolysis of structured triglyceride,1,3-dioleoyl-2-palmitoylglycerol, suggested that both the enzymes hydrolyse the fatty acids at both the positions. The observed discrimination against ω-3 fatty acids by PLA1 appears to be due to its fatty acid selectivity rather than positional specificity. These studies suggest that PLA1 could be used as a potential enzyme for selective concentrationof ω-3 fatty acids.

  16. Hydrophobicity and Retention Coefficient of Selected Bile Acid Oxo Derivatives

    NARCIS (Netherlands)

    Posa, Mihalj; Pilipovic, Ana; Lalic, Mladena; Popovic, Jovan

    2010-01-01

    Retention coefficients (k) of cholic acid and its keto derivatives are determined by means of Reversed Phase High Pressure Liquid Chromatography at different temperatures (303K, 309K, and 313K). At each studied temperature, retention factor decreases if the hydroxyl group in the cholic acid molecule

  17. Selective production of aromatics from alkylfurans over solid acid catalysts

    DEFF Research Database (Denmark)

    Wang, Dong; Dumesic, James A.; Taarning, Esben;

    2013-01-01

    for this reaction, because amorphous solid acids and homogeneous Brønsted acids demonstrate significant activity for p-xylene production. The production of p-xylene from 2,5-dimethylfuran proceeded at higher rates compared with the production of toluene and benzene from 2-methylfuran and furan, respectively. Both...

  18. The role of ammonia in sulfuric acid ion induced nucleation

    Directory of Open Access Journals (Sweden)

    I. K. Ortega

    2008-06-01

    Full Text Available We have developed a new multi-step strategy for quantum chemical calculations on atmospherically relevant cluster structures that makes calculation for large clusters affordable with a good accuracy-to-computational effort ratio. We have applied this strategy to evaluate the relevance of ternary ion induced nucleation; we have also performed calculations for neutral ternary nucleation for comparison. The results for neutral ternary nucleation agree with previous results, and confirm the important role of ammonia in enhancing the growth of sulfuric acid clusters. On the other hand, we have found that ammonia does not enhance the growth of ionic sulfuric acid clusters. The results also confirm that ion-induced nucleation is a barrierless process at high altitudes, but at ground level there exists a barrier due to the presence of a local minimum on the free energy surface.

  19. Cloud condensation nucleus behaviour of selected dicarboxylic acids

    DEFF Research Database (Denmark)

    Poulsen, Mia Frosch Mogensbæk; Nielsen, Ole Faurskov; Bilde, Merete

    .g. Anttila et al, 2005). Particles composed of two such compounds, namely glutaric acid and pimelic acid, have been studied using a cloud condensation nucleus counter (University of Wyoming, Model 100B). The behaviour of pimelic acid seems to agree quite well with the predictions of Köhler theory. This......, however, is not the case for glutaric acid. A likely explanation is that this rather volatile compound evaporates significantly from the surface of a particle. Attempts have therefore been made to correct for this evaporation, and the results show a much better agreement with Köhler theory. The...... Riekkola, M.L , Determination of organic acids in aerosol particles from a coniferous forest by liquid chromatography-mass spectrometry, Journal of Separation Science, 28, 337-346, 2005....

  20. Acidity of selected industrial wood species in Serbia

    Directory of Open Access Journals (Sweden)

    Popović Mlađan

    2016-01-01

    Full Text Available The acidity of wood has an important role in many areas of wood applications. Hence, this paper presents a study on the acidity of beech, fir and poplar, as the representatives of the most industrially utilized wood species in Serbia. The contents of both the soluble and insoluble acids were determined through the extraction methods with cold distilled water and sodium acetate solution, respectively, followed by the titration with sodium hydroxide solution. The acidity strongly differs among the three wood species used in this research. The amount of insoluble acids was the highest in fir, almost twice as much than in poplar, and about 68 % higher than in fir wood species. Such differences also showed a strong correlation with the gel times of UF adhesive mixes with hot water extracts. [Projekat Ministarstva nauke Republike Srbije, br. TP 31041: Establishment of Wood Plantations Intended for Afforestation of Serbia

  1. Docosahexaenoic acid induces apoptosis in primary chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Romain Guièze

    2015-12-01

    Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.

  2. Chromium-induced membrane damage: protective role of ascorbic acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80 - 100gbody weight). It has been observed that the intoxication with chromium ( i. p. ) at the dose of 0.8 mg/100g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospbolipid of both liver and kidney. The alkaline pbosphatase, total ATPase and Na + -K + -ATPase activities were significantly decreased in both liver and kidney after chromium treatment,except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid ( i.p. at the dose of 0.5 mg,/100g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  3. Ancillary effects of selected acid deposition control policies

    Energy Technology Data Exchange (ETDEWEB)

    Moe, R.J.; Lyke, A.J.; Nesse, R.J.

    1986-08-01

    NAPAP is examining a number of potential ways to reduce the precursors (sulfur dioxide and nitrogen oxides) to acid deposition. However, the policies to reduce acid deposition will have other physical, biological and economic effects unrelated to acid deposition. For example, control policies that reduce sulfur dioxide emissions may also increase visibility. The effects of an acid deposition policy that are unrelated to acid deposition are referred to as ''ancillary'' effects. This reserch identifies and characterizes the principle physical and economic ancillary effects associated with acid deposition control and mitigation policies. In this study the ancillary benefits associated with four specific acid deposition policy options were investigated. The four policy options investigated are: (1) flue gas desulfurization, (2) coal blending or switching, (3) reductions in automobile emissions of NO/sub x/, and (4) lake liming. Potential ancillary benefits of each option were identified and characterized. Particular attention was paid to the literature on economic valuation of potential ancillary effects.

  4. Dipeptidyl peptidase IV inhibition potentiates amino acid- and bile acid-induced bicarbonate secretion in rat duodenum.

    Science.gov (United States)

    Inoue, Takuya; Wang, Joon-Ho; Higashiyama, Masaaki; Rudenkyy, Sergiy; Higuchi, Kazuhide; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

    2012-10-01

    Intestinal endocrine cells release gut hormones, including glucagon-like peptides (GLPs), in response to luminal nutrients. Luminal L-glutamate (L-Glu) and 5'-inosine monophosphate (IMP) synergistically increases duodenal HCO3- secretion via GLP-2 release. Since L cells express the bile acid receptor TGR5 and dipeptidyl peptidase (DPP) IV rapidly degrades GLPs, we hypothesized that luminal amino acids or bile acids stimulate duodenal HCO3- secretion via GLP-2 release, which is enhanced by DPPIV inhibition. We measured HCO3- secretion with pH and CO2 electrodes using a perfused rat duodenal loop under isoflurane anesthesia. L-Glu (10 mM) and IMP (0.1 mM) were luminally coperfused with or without luminal perfusion (0.1 mM) or intravenous (iv) injection (3 μmol/kg) of the DPPIV inhibitor NVP728. The loop was also perfused with a selective TGR5 agonist betulinic acid (BTA, 10 μM) or the non-bile acid type TGR5 agonist 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide (CCDC; 10 μM). DPPIV activity visualized by use of the fluorogenic substrate was present on the duodenal brush border and submucosal layer, both abolished by the incubation with NVP728 (0.1 mM). An iv injection of NVP728 enhanced L-Glu/IMP-induced HCO3- secretion, whereas luminal perfusion of NVP728 had no effect. BTA or CCDC had little effect on HCO3- secretion, whereas NVP728 iv markedly enhanced BTA- or CCDC-induced HCO3- secretion, the effects inhibited by a GLP-2 receptor antagonist. Coperfusion of the TGR5 agonist enhanced L-Glu/IMP-induced HCO3- secretion with the enhanced GLP-2 release, suggesting that TGR5 activation amplifies nutrient sensing signals. DPPIV inhibition potentiated luminal L-Glu/IMP-induced and TGR5 agonist-induced HCO3- secretion via a GLP-2 pathway, suggesting that the modulation of the local concentration of the endogenous secretagogue GLP-2 by luminal compounds and DPPIV inhibition helps regulate protective duodenal HCO3- secretion.

  5. Dipeptidyl peptidase IV inhibition potentiates amino acid- and bile acid-induced bicarbonate secretion in rat duodenum.

    Science.gov (United States)

    Inoue, Takuya; Wang, Joon-Ho; Higashiyama, Masaaki; Rudenkyy, Sergiy; Higuchi, Kazuhide; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

    2012-10-01

    Intestinal endocrine cells release gut hormones, including glucagon-like peptides (GLPs), in response to luminal nutrients. Luminal L-glutamate (L-Glu) and 5'-inosine monophosphate (IMP) synergistically increases duodenal HCO3- secretion via GLP-2 release. Since L cells express the bile acid receptor TGR5 and dipeptidyl peptidase (DPP) IV rapidly degrades GLPs, we hypothesized that luminal amino acids or bile acids stimulate duodenal HCO3- secretion via GLP-2 release, which is enhanced by DPPIV inhibition. We measured HCO3- secretion with pH and CO2 electrodes using a perfused rat duodenal loop under isoflurane anesthesia. L-Glu (10 mM) and IMP (0.1 mM) were luminally coperfused with or without luminal perfusion (0.1 mM) or intravenous (iv) injection (3 μmol/kg) of the DPPIV inhibitor NVP728. The loop was also perfused with a selective TGR5 agonist betulinic acid (BTA, 10 μM) or the non-bile acid type TGR5 agonist 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide (CCDC; 10 μM). DPPIV activity visualized by use of the fluorogenic substrate was present on the duodenal brush border and submucosal layer, both abolished by the incubation with NVP728 (0.1 mM). An iv injection of NVP728 enhanced L-Glu/IMP-induced HCO3- secretion, whereas luminal perfusion of NVP728 had no effect. BTA or CCDC had little effect on HCO3- secretion, whereas NVP728 iv markedly enhanced BTA- or CCDC-induced HCO3- secretion, the effects inhibited by a GLP-2 receptor antagonist. Coperfusion of the TGR5 agonist enhanced L-Glu/IMP-induced HCO3- secretion with the enhanced GLP-2 release, suggesting that TGR5 activation amplifies nutrient sensing signals. DPPIV inhibition potentiated luminal L-Glu/IMP-induced and TGR5 agonist-induced HCO3- secretion via a GLP-2 pathway, suggesting that the modulation of the local concentration of the endogenous secretagogue GLP-2 by luminal compounds and DPPIV inhibition helps regulate protective duodenal HCO3- secretion. PMID:22821947

  6. Synergistic teratogenic effects induced by retinoids in mice by coadministration of a RARalpha- or RARgamma-selective agonist with a RXR-selective agonist.

    Science.gov (United States)

    Elmazar, M M; Rühl, R; Nau, H

    2001-01-01

    To study the interaction of retinoid-induced limb defects and cleft palate on day 11 of gestation, a RXR-selective agonist (AGN191701, an arylpropenyl-thiophene-carboxylic acid derivative, 20 mg/kg orally) was coadministered with a RARalpha-agonist (Am580, an arylcarboxamidobenzoic acid derivative, 5 mg/kg orally) to NMRI mice. AGN191701 was neither fetotoxic nor teratogenic at the dose used but potentiated Am580-induced limb defects and cleft palate and prevented Am580-induced fetal weight retardation. These results suggest that Am580-induced limb defects and probably cleft palate on day 11 of gestation may be mediated via RARalpha-RXR heterodimerization, particularly in the absence of toxicokinetic interactions. AGN191701 was also coadministered with a RARgamma-agonist (CD437, an adamantyl-hydroxyphenyl naphthoic acid derivative, 15 mg/kg orally) on days 8 and 11 of gestation to investigate which CD437-induced defects are mediated via RARgamma-RXR heterodimerization. On day 8 of gestation, AGN191701 potentiated CD437-induced embryolethality, exencephaly, spina bifida aperta, cleft palate, and tail defects, as well as visceral and skeletal defects, but not micrognathia. On day 11 of gestation, the incidence of CD437-induced cleft palate and limb defects was also potentiated when coadministered with the RXR agonist. These results suggest that synergistic teratogenic effects can be induced by coadministration of two receptor-selective retinoids, indicating the importance of RARalpha-RXR and RARgamma-RXR heterodimers in producing structural defects during organogenesis.

  7. Highly Selective Artificial K(+) Channels: An Example of Selectivity-Induced Transmembrane Potential.

    Science.gov (United States)

    Gilles, Arnaud; Barboiu, Mihail

    2016-01-13

    Natural KcsA K(+) channels conduct at high rates with an extraordinary selectivity for K(+) cations, excluding the Na(+) or other cations. Biomimetic artificial channels have been designed in order to mimick the ionic activity of KcSA channels, but simple artificial systems presenting high K(+)/Na(+) selectivity are rare. Here we report an artificial ion channel of H-bonded hexyl-benzoureido-15-crown-5-ether, where K(+) cations are highly preferred to Na(+) cations. The K(+)-channel conductance is interpreted as arising in the formation of oligomeric highly cooperative channels, resulting in the cation-induced membrane polarization and enhanced transport rates without or under pH-active gradient. These channels are selectively responsive to the presence of K(+) cations, even in the presence of a large excess of Na(+). From the conceptual point of view, these channels express a synergistic adaptive behavior: the addition of the K(+) cation drives the selection and the construction of constitutional polarized ion channels toward the selective conduction of the K(+) cation that promotes their generation in the first place.

  8. Neuroprotective effects of MK-801 on L-2-chloropropionic acid-induced neurotoxicity.

    Science.gov (United States)

    Williams, R E; Lock, E A; Bachelard, H S

    2001-02-01

    L-2-Chloropropionic acid is selectively toxic to the cerebellum in rats; the granule cell necrosis observed within 48 h can be prevented by prior administration of MK-801. Short-term treatment (2 h) with L-2-chloropropionic acid has also been shown to activate the mitochondrial pyruvate dehydrogenase complex in fasted adult rats. This study aimed to investigate the effect of prior exposure to MK-801 on the biochemical and neurotoxicological effects of L-2-chloropropionic acid. Extracts were prepared from the forebrain and cerebellum of animals that had been treated with L-2-chloropropionic acid, with and without prior treatment with MK-801, and were analysed using magnetic resonance spectroscopy and amino acid analysis. Glucose metabolism was studied by monitoring the metabolism of [1-(13)C]-glucose using GC/MS. L-2-Chloropropionic acid caused increased glucose metabolism in both brain regions 6 h after administration, confirming activation of the pyruvate dehydrogenase complex, which was not prevented by MK-801. After 48 h an increase in lactate and a decrease in N-acetylaspartate was observed only in the cerebellum, whereas phosphocreatine and ATP decreased in both tissues. MK-801 prevented the changes in lactate and N:-acetylaspartate, but not those on the energy state. These studies suggest that L-2-chloropropionic acid-induced neurotoxicity is only partly mediated by the NMDA subtype of glutamate receptor.

  9. Content of amino acids and minerals in selected sorts of legumes

    OpenAIRE

    Stanislav Kráčmar; Pavel Švec; Petra Vojtíšková

    2013-01-01

    The aim of this study was to determine amino acid composition and mineral content in selected legume samples. All analyses were carried out at the laboratory temperature of 21±2 °C in triplicate. Amino acid composition was determined using the automatic amino acid analyzer AAA 400 with post-column derivatization. To assess the nutritional value of protein, index of essential amino acids (EAAI) was calculated. Minerals were determined using the atomic absorption spectrometer AA 30. All resu...

  10. Selective Induced Altered Coccidians to Immunize and Prevent Enteritis

    Science.gov (United States)

    2016-01-01

    Microbiomic flora in digestive tract is pivotal to the state of our health and disease. Antibiotics affect GI, control composition of microbiome, and shift equilibrium from health into disease status. Coccidiosis causes gastrointestinal inflammation. Antibiotic additives contaminate animal products and enter food chain, consumed by humans with possible allergic, antibiotic resistance and enigmatic side effects. Purposed study induced nonpathogenic, immunogenic organisms to protect against disease and abolish antibiotics' use in food animals and side effects in man. Diverse species of Coccidia were used as model. Immature organisms were treated with serial purification procedure prior to developmental stages to obtain altered strains. Chicks received oral gavage immunized with serial low doses of normal or altered organisms or sham treatment and were challenged with high infective normal organisms to compare pathogenicity and immunogenicity. Mature induced altered forms of E. tenella and E. necatrix lacked developmental stage of “sporocysts” and contained free sporozoites. In contrast, E. maxima progressed to normal forms or did not mature at all. Animals that received altered forms were considerably protected with higher weight gain and antibody titers against challenge infection compared to those that received normal organisms (p < 0.05). This is the first report to induce selected protective altered organisms for possible preventive measures to minimize antibiotic use in food animals. PMID:27721824

  11. Folic acid induces salicylic acid-dependent immunity in Arabidopsis and enhances susceptibility to Alternaria brassicicola.

    Science.gov (United States)

    Wittek, Finni; Kanawati, Basem; Wenig, Marion; Hoffmann, Thomas; Franz-Oberdorf, Katrin; Schwab, Wilfried; Schmitt-Kopplin, Philippe; Vlot, A Corina

    2015-08-01

    Folates are essential for one-carbon transfer reactions in all organisms and contribute, for example, to de novo DNA synthesis. Here, we detected the folate precursors 7,8-dihydropteroate (DHP) and 4-amino-4-deoxychorismate (ADC) in extracts from Arabidopsis thaliana plants by Fourier transform ion cyclotron resonance-mass spectrometry. The accumulation of DHP, but not ADC, was induced after infection of plants with Pseudomonas syringae delivering the effector protein AvrRpm1. Application of folic acid or the DHP precursor 7,8-dihydroneopterin (DHN) enhanced resistance in Arabidopsis to P. syringae and elevated the transcript accumulation of the salicylic acid (SA) marker gene pathogenesis-related1 in both the treated and systemic untreated leaves. DHN- and folic acid-induced systemic resistance was dependent on SA biosynthesis and signalling. Similar to SA, folic acid application locally enhanced Arabidopsis susceptibility to the necrotrophic fungus Alternaria brassicicola. Together, the data associate the folic acid pathway with innate immunity in Arabidopsis, simultaneously activating local and systemic SA-dependent resistance to P. syringae and suppressing local resistance to A. brassicicola.

  12. Systemic resistance in Arabidopsis induced by biocontrol bacteria is independent of salicylic acid accumulation and pathogenesis-related gene expression

    NARCIS (Netherlands)

    Pieterse, C.M.J.; Wees, A.C.M. van; Hoffland, E.; Pelt, J.A. van; Loon, L.C. van

    1996-01-01

    Systemic acquired resistance is a pathogen-inducible defense mechanism in plants. The resistant state is dependent on endogenous accumulation of salicylic acid (SA) and is characterized by the activation of genes encoding pathogenesis-related (PR) proteins. Recently, selected nonpathogenic, root-col

  13. Valproic acid induces antimicrobial compound production in Doratomyces microspores.

    Directory of Open Access Journals (Sweden)

    Christoph eZutz

    2016-04-01

    Full Text Available One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called cryptic, often silenced, compounds. These putative metabolites could include novel bioactive compounds. Considerable effort is spent on methods to induce production of these cryptic metabolites. One approach is the use of small molecule effectors, potentially influencing chromatin landscape in fungi. We observed that the supernatant of the fungus Doratomyces (D. microsporus treated with valproic acid (VPA displayed antimicrobial activity against Staphylococcus (S. aureus and two methicillin resistant clinical S. aureus isolates. VPA treatment resulted in enhanced production of seven antimicrobial compounds: cyclo-(L-proline-L-methionine (cPM, p-hydroxybenzaldehyde, cyclo-(phenylalanine-proline (cFP, indole-3-carboxylic acid, phenylacetic acid (PAA and indole-3-acetic acid. The production of the antimicrobial compound phenyllactic acid was exclusively detectable after VPA treatment. Furthermore three compounds, cPM, cFP and PAA, were able to boost the antimicrobial activity of other antimicrobial compounds. cPM, for the first time isolated from fungi, and to a lesser extent PAA, are even able to decrease the minimal inhibitory concentration of ampicillin in MRSA strains. In conclusion we could show in this study that VPA treatment is a potent tool for induction of cryptic antimicrobial compound production in fungi, and that the induced compounds are not exclusively linked to the secondary metabolism. Furthermore this is the first discovery of the rare diketopiperazine cPM in fungi. Additionally we could demonstrate that cPM and PAA boost antibiotic activity against

  14. Valproic Acid Induces Antimicrobial Compound Production in Doratomyces microspores

    Science.gov (United States)

    Zutz, Christoph; Bacher, Markus; Parich, Alexandra; Kluger, Bernhard; Gacek-Matthews, Agnieszka; Schuhmacher, Rainer; Wagner, Martin; Rychli, Kathrin; Strauss, Joseph

    2016-01-01

    One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called “cryptic,” often silenced, compounds. These putative metabolites could include novel bioactive compounds. Considerable effort is spent on methods to induce production of these “cryptic” metabolites. One approach is the use of small molecule effectors, potentially influencing chromatin landscape in fungi. We observed that the supernatant of the fungus Doratomyces (D.) microsporus treated with valproic acid (VPA) displayed antimicrobial activity against Staphylococcus (S.) aureus and two methicillin resistant clinical S. aureus isolates. VPA treatment resulted in enhanced production of seven antimicrobial compounds: cyclo-(L-proline-L-methionine) (cPM), p-hydroxybenzaldehyde, cyclo-(phenylalanine-proline) (cFP), indole-3-carboxylic acid, phenylacetic acid (PAA) and indole-3-acetic acid. The production of the antimicrobial compound phenyllactic acid was exclusively detectable after VPA treatment. Furthermore three compounds, cPM, cFP, and PAA, were able to boost the antimicrobial activity of other antimicrobial compounds. cPM, for the first time isolated from fungi, and to a lesser extent PAA, are even able to decrease the minimal inhibitory concentration of ampicillin in MRSA strains. In conclusion we could show in this study that VPA treatment is a potent tool for induction of “cryptic” antimicrobial compound production in fungi, and that the induced compounds are not exclusively linked to the secondary metabolism. Furthermore this is the first discovery of the rare diketopiperazine cPM in fungi. Additionally we could demonstrate that cPM and PAA boost antibiotic activity

  15. Modeling of the selective pertraction of carboxylic acids obtained by citric fermentation

    Directory of Open Access Journals (Sweden)

    Cascaval Dan

    2004-01-01

    Full Text Available Facilitated pertraction was applied for the selective separation of citric, maleic and succinic acids from a mixture obtained by citric fermentation. The pertraction equipment included a U-shaped cell containing 1,2-dichloro-ethane as the liquid membrane and Amberlite LA-2 as the carrier. The experimental data indicated that maleic and succinic acids can be initially selectively separated from citric acid, followed by the selectively separation of maleic acid from succinic acid. Using statistical analysis and a second order factorial experiment, two mathematical correlations describing the influence of the main process variables on pertraction selectivity were established. For both extraction systems, the considered variables controlled the extraction process to an extent of 92.9-99.9%, the carrier concentration inside the liquid membrane exhibiting the most important influence.

  16. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    International Nuclear Information System (INIS)

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  17. Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Lili eGao

    2015-10-01

    Full Text Available Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA, a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition and activation of tansforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

  18. Lewis Acid Catalyzed Selective Reactions of Donor-Acceptor Cyclopropanes with 2-Naphthols.

    Science.gov (United States)

    Kaicharla, Trinadh; Roy, Tony; Thangaraj, Manikandan; Gonnade, Rajesh G; Biju, Akkattu T

    2016-08-16

    Lewis acid-catalyzed reactions of 2-substituted cyclopropane 1,1-dicarboxylates with 2-naphthols is reported. The reaction exhibits tunable selectivity depending on the nature of Lewis acid employed and proceed as a dearomatization/rearomatization sequence. With Bi(OTf)3 as the Lewis acid, a highly selective dehydrative [3+2] cyclopentannulation takes place leading to the formation of naphthalene-fused cyclopentanes. Interestingly, engaging Sc(OTf)3 as the Lewis acid, a Friedel-Crafts-type addition of 2-naphthols to cyclopropanes takes place, thus affording functionalized 2-naphthols. Both reactions furnished the target products in high regioselectivity and moderate to high yields. PMID:27391792

  19. Selective separation of indium by iminodiacetic acid chelating resin

    Energy Technology Data Exchange (ETDEWEB)

    Fortes, M.C.B.; Benedetto, J.S. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Martins, A.H. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Metalurgica e de Materiais]. E-mail: ahmartin@demet.ufmg.br

    2007-04-15

    - Indium can be recovered by treating residues, flue dusts, slags, and metallic intermediates in zinc smelting. This paper investigates the adsorption characteristics of indium and iron on an iminodiacetic acid chelating resin, Amberlite{sup R} IRC748 (Rohm and Haas Co.-USA). High concentrations of iron are always present in the aqueous feed solution of indium recovery. In addition, the chemical behaviour of iron in adsorptive systems is similar to that of indium. The metal concentrations in the aqueous solution were based on typical indium sulfate leach liquor obtained from zinc hydrometallurgical processing in a Brazilian plant. The ionic adsorption experiments were carried out by the continuous column method. Amberlite{sup R} IRC748 resin had a high affinity for indium under acidic conditions. Indium ions adsorbed onto the polymeric resin were eluted with a 0.5 mol/dm{sup 3} sulphuric acid solution passed through the resin bed in the column. 99.5% pure indium sulfate aqueous solution was obtained using the iminodiacetic acid chelating resin Amberlite{sup R} IRC748. (author)

  20. [Effect of excitant amino acid antagonists on glutamate receptors in the locust and on convulsions induced by glutamate, aspartate, kynurenine and quinolinic acid in mice].

    Science.gov (United States)

    Ryzhov, I V; Slepokurov, M V; Lapin, I P; Mandel'shtam, Iu E; Aleksandrov, V G

    1986-03-01

    All excitatory amino acid antagonists studied: diethyl esters of aspartic (DEEA) and glutamic (DEEG) acids, 2-amino-3-phosphono-propionic acid (APPA) and 2-amino-4-phosphono-butanoic acid (APBA), diminished the amplitude of excitatory postsynaptic potentials (EPP) of the locust (Locusta migratoria migratorioides) muscle fibers and arbitrary blocked glutamate (GLU) and aspartate (ASP) responses. Kynurenine (KYN) and quinolinic (QUI) acid had no effect on EPP even at a concentration of 2 X 10(-2) M. The antagonists were not strictly selective against intracerebroventricularly administered endogenous convulsants: GLU, ASP, KYN and QUI and in simulation of experimental seizures in mice. The antagonists structurally similar to ASP prevented ASP- and KYN-induced seizures in lower doses than GLU derivatives. Anti-KYN, but not anti-QUI DEEA, DEEG, APPA and APBA efficacy suggests that KYN and QUI act on different structures or binding sites. PMID:2869799

  1. Regulation of Water Deficit-Induced Abscisic Acid Accumulation by Apoplastic Ascorbic Acid in Maize Seedlings

    Institute of Scientific and Technical Information of China (English)

    Jian-Fang HU; Gui-Fen LI; Zhi-Hui GAO; Lin CHEN; Hui-Bo REN; Wen-Suo JIA

    2005-01-01

    Water deficit-induced abscisic acid (ABA) accumulation is one of the most important stress signaling pathways in plant cells. Redox regulation of cellular signaling has currently attracted particular attention, but much less is known about its roles and mechanisms in plant signaling. Herein, we report that water deficit-induced ABA accumulation could be regulated by ascorbic acid (AA)-controlled redox status in leave apoplast. The AA content in non-stressed leaves was approximately 3 μmol/g FW, corresponding to a mean concentration of 3 mmol/L in a whole cell. Because AA is mainly localized in the cytosol and chloroplasts, the volume of which is much smaller than that of the whole cell, AA content in cytosolic and chloroplast compartments should be much higher than 3 mmol/L. Water deficit-induced ABA accumulation in both leaf and root tissues of maize seedlings was significantly inhibited by AA and reduced glutathione (GSH) at concentrations of 500 μmol/L and was completely blocked by 50 mmol/L AA and GSH. These results suggest that the AA-induced inhibition of ABA accumulation should not occur at sites where AA exists in high concentrations. Although water deficit led to a small increase in the dehydroascorbic acid (DHA) content, no significant changes in AA content were observed in either leaf or root tissues. When compared with the whole leaf cell, the AA content in the apoplastic compartment was much lower (i.e.approximately 70 nmol/g FW, corresponding to 0.7 mmol/L). Water deficit induced a significant decrease (approximately 2.5-fold) in the AA content and an increase (approximately 3.4-fold) in the DHA content in the apoplastic compartment, thus leading to a considerably decreased redox status there, which may have contributed to the relief of AA-induced inhibition of ABA accumulation, alternatively, promoting water deficit-induced ABA accumulation. Reactive oxygen species (ROS) could not mimic water deficit in inducing ABA accumulation, suggesting that

  2. Radiation induced crystallinity damage in poly(L-lactic acid)

    CERN Document Server

    Kantoglu, O

    2002-01-01

    The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

  3. Ursolic acid improves domoic acid-induced cognitive deficits in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong-mei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Lu, Jun, E-mail: lu-jun75@163.com [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-lin, E-mail: ylzheng@xznu.edu.cn [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Cheng, Wei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zhang, Zi-feng; Li, Meng-qiu [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China)

    2013-09-01

    Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.

  4. Pattern of Limb Malformations in Mice Induced by Methoxyacetic Acid

    OpenAIRE

    Rasjad, Chairuddin; Yamashita, Keisuke; Datu, Abdul Razak; Yasuda, Mineo

    1991-01-01

    The present study investigated the pattern of limb malformations induced in mice by methoxyacetic acid (MAA), one of di(2-methoxyethyl) phthalate (DMEP) metabolites. Pregnant Jcl:ICR mice were given orally at gestational day (gd) 10.5, 11.0, or 11.5 (vaginal plug = gd 0) a single dose of MAA 10 mmol/kg of body weight. Fetuses were examined at gd 15.5 for external and skeletal malformations. Limb defects were maximum in frequency and severity after administration at gd 11.5. Forelimbs had grea...

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

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

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

  6. Melatonin ameliorated okadaic-acid induced Alzheimer-like lesions

    Institute of Scientific and Technical Information of China (English)

    Yi-peng WANG; Xian-tao LI; Shi-jie LIU; Xin-wen ZHOU; Xiao-chuan WANG; Jian-zhi WANG

    2004-01-01

    AIM: To explore the protective effects of melatonin (Mel) on the abnormal phosphorylation of neuronal cytoskeletal proteins. METHODS: We generated a neuroblastoma (SH-SY5Y) cell system in which cytoskeletal proteins are abnormally phosphorylated resulting in microtubule disruption due to the marked inhibition of protein phosphatase activities by okadaic acid (OA). RESULTS: OA-induced declines in cell viability and mitochondrial metabolic activity were remarkably prevented by Mel. In addition, the hyperphosphorylation/accumulation of neurofilament(NF-) H/M subunits and the disruption of microtubules, induced by OA, were significantly inhibited by Mel.CONCLUSION: Our results suggest multiple protective functions of Mel against a series of pathological lesions known to culminate in AD, including abnormal phosphorylation of cytoskeletal proteins, microtubule disassembly and mitochondrion-initiated cell toxicity.

  7. Benzoic Acid-Inducible Gene Expression in Mycobacteria.

    Directory of Open Access Journals (Sweden)

    Marte S Dragset

    Full Text Available Conditional expression is a powerful tool to investigate the role of bacterial genes. Here, we adapt the Pseudomonas putida-derived positively regulated XylS/Pm expression system to control inducible gene expression in Mycobacterium smegmatis and Mycobacterium tuberculosis, the causative agent of human tuberculosis. By making simple changes to a Gram-negative broad-host-range XylS/Pm-regulated gene expression vector, we prove that it is possible to adapt this well-studied expression system to non-Gram-negative species. With the benzoic acid-derived inducer m-toluate, we achieve a robust, time- and dose-dependent reversible induction of Pm-mediated expression in mycobacteria, with low background expression levels. XylS/Pm is thus an important addition to existing mycobacterial expression tools, especially when low basal expression is of particular importance.

  8. Hydrodynamic flows can induce selective advantages among species

    Science.gov (United States)

    Tesser, Francesca; Benzi, Roberto; Clercx, Herman J. H.; Nelson, David R.; Perlekar, Prasad; Toschi, Federico

    2013-11-01

    Evolutionary forces such as genetic drift, selection, mutation and spatial diffusion act to change the genetic composition of populations. Such problems can be modeled as a system of binary reactions between competing individuals, involving births and deaths, and progressing at specific rates. An inhomogeneous or time-dependent spatial structure has the effect of modulating the interaction between individuals. To explore this problem further, we consider the dynamics and evolution of genetically diverse populations in a fluid environment where a flow field transports individuals in combination with birth and death processes, thus driving genetic inhomogeneities. An individual-based model in continuous space with spatial diffusion implements stochastic demographic rules for a fluctuating population size and introduces the advection of simple realistic flow fields. The system is analyzed in terms of fixation probabilities and fixation times as well as the behavior of spatial correlations. Provided organismic reproduction times are faster than the characteristic time scales of the flow, fluid ecosystems can by themselves induce spatially non-homogeneous selective advantages.

  9. DC diaphragm discharge in water solutions of selected organic acids

    Science.gov (United States)

    Vyhnankova, Edita J.; Hammer, Malte U.; Reuter, Stephan; Krcma, Frantisek

    2015-07-01

    Effect of four simple organic acids water solution on a DC diaphragm discharge was studied. Efficiency of the discharge was quantified by the hydrogen peroxide production determined by UV-VIS spectrometry of a H2O2 complex formed with specific titanium reagent. Automatic titration was used to study the pH behaviour after the plasma treatment. Optical emission spectroscopy overview spectra were recorded and detailed spectra of OH band and Hβ line were used to calculate the rotational temperature and comparison of the line profile (reflecting electron concentration) in the acid solutions. Contribution to the topical issue "The 14th International Symposium on High Pressure Low Temperature Plasma Chemistry (HAKONE XIV)", edited by Nicolas Gherardi, Ronny Brandenburg and Lars Stollenwark

  10. Chiral morphology of calcite through selective binding of amino acids

    Science.gov (United States)

    Orme, Christine

    2002-03-01

    Many living organisms contain biominerals and composites with finely tuned properties, reflecting a remarkable level of control over the nucleation, growth and shape of the constituent crystals. Peptides and proteins play an important role in achieving this control. Using in situ AFM we find that site-specific binding of amino acid residues to surface steps changes the step-edge free energies, giving rise to direction-specific binding energies unique to individual amino acid enantiomers and leading to chiral modifications that propagate from atomic length scales to macroscopic length scales. Molecular modeling studies support an energetic basis for the differences in binding. Our results emphasize that the mechanism under-lying crystal modification through organic molecules is best understood by considering both stereochemical recognition as well as the effects of binding on the interfacial energies of the growing crystal.

  11. Sensitization for Anticancer Drug-Induced Apoptosis by Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2005-02-01

    Full Text Available We previously described that betulinic acid (BetA, a naturally occurring pentacyclic triterpenoid, induces apoptosis in tumor cells through the mitochondrial pathway. Here, for the first time, we provide evidence that BetA cooperated with anticancer drugs to induce apoptosis and to inhibit clonogenic survival of tumor cells. Combined treatment with BetA and anticancer drugs acted in concert to induce loss of mitochondrial membrane potential and the release of cytochrome c and Smac from mitochondria, resulting in activation of caspases and apoptosis. Overexpression of Bcl-2, which blocked mitochondrial perturbations, also inhibited the cooperative effect of BetA and anticancer drugs, indicating that cooperative interaction involved the mitochondrial pathway. Notably, cooperation of BetA and anticancer drugs was found for various cytotoxic compounds with different modes of action (e.g., doxorubicin, cisplatin, Taxol, VP16, or actinomycin D. Importantly, BetA and anticancer drugs cooperated to induce apoptosis in different tumor cell lines, including p53 mutant cells, and also in primary tumor cells, but not in human fibroblasts indicating some tumor specificity. These findings indicate that using BetA as sensitizer in chemotherapy-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy, which warrants further investigation.

  12. Co-culture-inducible bacteriocin production in lactic acid bacteria.

    Science.gov (United States)

    Chanos, Panagiotis; Mygind, Tina

    2016-05-01

    It is common knowledge that microorganisms have capabilities, like the production of antimicrobial compounds, which do not normally appear in ideal laboratory conditions. Common antimicrobial discovery techniques require the isolation of monocultures and their individual screening against target microorganisms. One strategy to achieve expression of otherwise hidden antimicrobials is induction by co-cultures. In the area of bacteriocin-producing lactic acid bacteria, there has been some research focusing into the characteristics of co-culture-inducible bacteriocin production and particularly the molecular mechanism(s) of such interactions. No clear relationship has been seen between bacteriocin-inducing and bacteriocin-producing microorganisms. The three-component regulatory system seems to be playing a central role in the induction, but inducing compounds have not been identified or characterized. However, the presence of the universal messenger molecule autoinducer-2 has been associated in some cases with the co-culture-inducible bacteriocin phenotype and it may play the role in the additional regulation of the three-component regulatory system. Understanding the mechanisms of induction would facilitate the development of strategies for screening and development of co-culture bacteriocin-producing systems and novel products as well as the perseverance of such systems in food and down to the intestinal tract, possibly conferring a probiotic effect on the host. PMID:27037694

  13. Insights on FXR selective modulation. Speculation on bile acid chemical space in the discovery of potent and selective agonists

    Science.gov (United States)

    Sepe, Valentina; Festa, Carmen; Renga, Barbara; Carino, Adriana; Cipriani, Sabrina; Finamore, Claudia; Masullo, Dario; del Gaudio, Federica; Monti, Maria Chiara; Fiorucci, Stefano; Zampella, Angela

    2016-01-01

    Bile acids are the endogenous modulators of the nuclear receptor FXR and the membrane receptor GPBAR1. FXR represents a promising pharmacological target for the treatment of cholestatic liver disorders. Currently available semisynthetic bile acid derivatives cover the same chemical space of bile acids and therefore they are poorly selective toward BA receptors, increasing patient risk for adverse side effects. In this report, we have investigated around the structure of CDCA describing the synthesis and the in vitro and in vivo pharmacological characterization of a novel family of compounds modified on the steroidal tetracyclic core and on the side chain. Pharmacological characterization resulted in the identification of several potent and selective FXR agonists. These novel agents might add utility in the treatment of cholestatic disorders by potentially mitigating side effects linked to unwanted activation of GPBAR1. PMID:26740187

  14. Docosahexaenoic acid, an omega-3 polyunsaturated acid protects against indomethacin-induced gastric injury.

    Science.gov (United States)

    Pineda-Peña, Elizabeth Arlen; Jiménez-Andrade, Juan Miguel; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

    2012-12-15

    Previous studies have shown gastroprotective effect of fish oil in several experimental models. However, the mechanisms and active compounds underlying this effect are not fully understood. Fish oil has several components; among them, one of the most studied is docosahexaenoic acid (DHA), which is an omega-3 long-chain polyunsaturated fatty acid. The aim of this study was to examine the gastroprotective effect of DHA as a pure compound in a rat model of indomethacin-induced gastric injury as well as elucidate some of the mechanism(s) behind DHA's gastroprotective effect. Indomethacin was orally administered to induce an acute gastric injury (3, 10 and 30mg/kg). Omeprazol (a proton pump inhibitor, 30mg/kg, p.o.) and DHA (3, 10, 30mg/kg, p.o.) were gavaged 30 and 120min, respectively, before indomethacin insult (30mg/kg p.o.). Three hours after indomethacin administration, rats were sacrificed, gastric injury was evaluated by determining the total damaged area. A sample of gastric tissue was harvested and processed to quantify prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) levels by enzyme-linked immunosorbent assay. Indomethacin produced gastric injury in dose-dependent manner. DHA protected against indomethacin-induced gastric damage, and this effect was comparable with omeprazol's gastroprotective effect. DHA did not reverse the indomethacin-induced reduction of PGE(2) gastric levels. In contrast, DHA partially prevented the indomethacin-induced increase in LTB(4) gastric levels. This is the first report demonstrating DHA's gastroprotective effect as a pure compound. Furthermore, the results reveal that the gastroprotective effect is mediated by a decrease in gastric LTB(4) levels in indomethacin-induced gastric damage. PMID:23063544

  15. The Effect of Opsteoporotic Model Rats Induced by Retinoic Acid

    Institute of Scientific and Technical Information of China (English)

    Xu Peng; Yao Jianfeng; Jin Weizhang; Cai Qiankun; Guo Xiong

    2005-01-01

    Objective: To study the effect of retinoic acid on inducing osteoporosis in female rat. Methods: 48SD female rats were divided randomly into experiment group and control group. Retinoic acid was administered orally to experiment group with 80mg.kg-1d-1 for 15 days. Then the rats were sacrificed on the 0th, 30th, 60th days after last administration. The serum concentration of Ca, P, BGP, E2, AKP and TRAP were detected. Components of collagen and proteoglycan in the bones and BMD were also assayed .The femoral morphometric change and epiphyseal plate cartilage histological changes were observed. Results: After a 15-day period treatment with retinoic acid, charateristics of experiment group were compared with control, it is shown that the concentration of serum E2 and BGP declined, the activity of AKP and TRAP increased while BMP decreased, the bone mass of both spongy bone and cortical bone reduced, the number of spongy bone osteoclasts and their activity increased, number of epiphyseal plate chondrocyte reduced, cartilage hypertrophic zone displayed dyscalcification, and no difference of other markers was found in the two groups. On the 30th day after the last administration, the experiment group appeared a declined number of cancellous bone osteoclast and level of serum AKP yet they were still higher than control. Number of epiphyseal chondrocyte, serum BGP and tibial BMD, though higher than before, were still lower than control. Other markers were no difference. On the 60th day after treatment, although the femoral cancellous bone mass was still less and cancellous osteoblast was more than control, the cortical bone mass, cancellous osteoclast number and level of serum Ca and P were all remained no different between two groups.Conclusion: Retinoic acid possessed a better short-term effect than long-term effect. Cancellous bone loss lasted much longer than cortical bone and more obviously; the bone matrix in this osteoporosis model was able to repair itself

  16. Selective Enrichment of Omega-3 Fatty Acids in Oils by Phospholipase A1.

    Science.gov (United States)

    Ranjan Moharana, Tushar; Byreddy, Avinesh R; Puri, Munish; Barrow, Colin; Rao, Nalam Madhusudhana

    2016-01-01

    Omega fatty acids are recognized as key nutrients for healthier ageing. Lipases are used to release ω-3 fatty acids from oils for preparing enriched ω-3 fatty acid supplements. However, use of lipases in enrichment of ω-3 fatty acids is limited due to their insufficient specificity for ω-3 fatty acids. In this study use of phospholipase A1 (PLA1), which possesses both sn-1 specific activity on phospholipids and lipase activity, was explored for hydrolysis of ω-3 fatty acids from anchovy oil. Substrate specificity of PLA1 from Thermomyces lenuginosus was initially tested with synthetic p-nitrophenyl esters along with a lipase from Bacillus subtilis (BSL), as a lipase control. Gas chromatographic characterization of the hydrolysate obtained upon treatment of anchovy oil with these enzymes indicated a selective retention of ω-3 fatty acids in the triglyceride fraction by PLA1 and not by BSL. 13C NMR spectroscopy based position analysis of fatty acids in enzyme treated and untreated samples indicated that PLA1 preferably retained ω-3 fatty acids in oil, while saturated fatty acids were hydrolysed irrespective of their position. Hydrolysis of structured triglyceride,1,3-dioleoyl-2-palmitoylglycerol, suggested that both the enzymes hydrolyse the fatty acids at both the positions. The observed discrimination against ω-3 fatty acids by PLA1 appears to be due to its fatty acid selectivity rather than positional specificity. These studies suggest that PLA1 could be used as a potential enzyme for selective concentrationof ω-3 fatty acids. PMID:26978518

  17. Introduction of structural affinity handles as a tool in selective nucleic acid separations

    Science.gov (United States)

    Willson, III, Richard Coale (Inventor); Cano, Luis Antonio (Inventor)

    2011-01-01

    The method is used for separating nucleic acids and other similar constructs. It involves selective introduction, enhancement, or stabilization of affinity handles such as single-strandedness in the undesired (or desired) nucleic acids as compared to the usual structure (e.g., double-strandedness) of the desired (or undesired) nucleic acids. The undesired (or desired) nucleic acids are separated from the desired (or undesired) nucleic acids due to capture by methods including but not limited to immobilized metal affinity chromatography, immobilized single-stranded DNA binding (SSB) protein, and immobilized oligonucleotides. The invention is useful to: remove contaminating genomic DNA from plasmid DNA; remove genomic DNA from plasmids, BACs, and similar constructs; selectively separate oligonucleotides and similar DNA fragments from their partner strands; purification of aptamers, (deoxy)-ribozymes and other highly structured nucleic acids; Separation of restriction fragments without using agarose gels; manufacture recombinant Taq polymerase or similar products that are sensitive to host genomic DNA contamination; and other applications.

  18. Induced resistance by cresotic acid (3-hydroxy-4-methyl methylbenzoic acid) against wilt disease of melon and cotton

    International Nuclear Information System (INIS)

    Cresotic acid (3-hydroxy-4-methylbenzoic acid) was proved be active in controlling wilt diseases of melon and cotton plants grown in the house. Soil drench with 200-1000 ppm cresotic acid induced 62-77 %, 69-79 % and 50-60 % protection against Fusarium oxysporum f.sp melonis (FOM) in melon, Fusarium oxysporum f.sp vasinfectum (FOV) and Verticillium dahliae in cotton, respectively. Since no inhibitory effect of cresotic acid on mycelial growth of these three fungual pathogens was observed in vitro, it is suggested that control of these wilt diseases with cresotic acid resulted from induced resistance. Cresotic acid induced resistance in melon plants not only against race 0, race 1, race 2 and race 1,2, but also against a mixture of these four races of FOM, suggesting a non-race- specific resistance. Level of induced resistance by cresotic acid against FOM depended on inoculum pressure applied to melon plants. At 25 day after inoculation with FOM, percentage protection induced by cresotic acid under low inoculum pressure retained a level of 51 %, while under high inoculum pressure percentage protection decreased to only 10 %. High concentrations of cresotic acid significantly reduced plant growth. Reduction in fresh weight of melon (36-51%) and cotton (42-71%) was obtained with 500-1000 ppm cresotic acid, while only less than 8% reduction occurred with 100-200 ppm. (author)

  19. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Science.gov (United States)

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels. PMID:26571019

  20. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Science.gov (United States)

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  1. Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

    Directory of Open Access Journals (Sweden)

    Yoshihiro Akimoto

    2014-06-01

    Full Text Available Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488. However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

  2. Radiation-induced electron migration in nucleic acids

    International Nuclear Information System (INIS)

    Radiation-induced electron migration along DNA is a mechanism by which randomly produced stochastic energy deposition events can lead to non-random types of damage along DNA manifested distal to the sites of the initial energy deposition. Radiation-induced electron migration in nucleic acids has been examined using oligonucleotides containing 5-bromouracil (5-BrU). Interaction of 5-BrU with solvated electrons results in release of bromide ions and formation of uracil-5-yl radicals. Monitoring either bromide ion release or uracil formation provides an opportunity to study electron migration processes in model nucleic acid systems. Using this approach we have discovered that electron migration along oligonucleotides is significantly influenced by the base sequence and strandedness. Migration along 7 base pairs in oligonucleotides containing guanine bases was observed for oligonucleotides irradiated in solution, which compares with mean migration distances of 6-10 bp for Escherichia coli DNA irradiated in solution and 5.5 bp for E. coli DNA irradiated in cells. Evidence also suggests that electron migration can occur preferentially in the 5' to 3' direction along a double-stranded oligonucleotide containing a region of purine bases adjacent to the 5-BrU moiety. Our continued efforts will provide information regarding the contribution of electron transfer along DNA to formation of locally multiply damaged sites created in DNA by exposure to ionizing radiation. (Author)

  3. Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists at group I metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Madsen, U; Bräuner-Osborne, H; Frydenvang, Karla Andrea;

    2001-01-01

    to originate in (S)-11 (EC(50) = 395 microM, K(b) = 86 and 90 microM, respectively). Compound 9, administered icv, but not sc, was shown to protect mice against convulsions induced by N-methyl-D-aspartic acid (NMDA). Compounds 9 and 11 were resolved using chiral HPLC, and the configurational assignments...

  4. Selective Oxidative Decarboxylation of Amino Acids to Produce Industrially Relevant Nitriles by Vanadium Chloroperoxidase

    NARCIS (Netherlands)

    But, A.; Notre, le J.E.L.; Scott, E.L.; Wever, R.; Sanders, J.P.M.

    2012-01-01

    Industrial nitriles from biomass: Vanadium-chloroperoxidase is successfully used to transform selectively glutamic acid into 3-cyanopropanoic acid, a key intermediate for the synthesis of bio-succinonitrile and bio-acrylonitrile, by using a catalytic amount of a halide salt. This clean oxidative dec

  5. Selecting lactic acid bacteria for their safety and functionality by use of a mouse colitis model.

    Science.gov (United States)

    Daniel, Catherine; Poiret, Sabine; Goudercourt, Denise; Dennin, Veronique; Leyer, Gregory; Pot, Bruno

    2006-09-01

    Studies showed that specific probiotics might provide therapeutic benefits in inflammatory bowel disease. However, a rigorous screening of new probiotics is needed to study possible adverse interactions with the host, particularly when intended for administration to individuals with certain health risks. In this context, the objective of this study was to investigate the role of three lactobacilli (LAB) on intestinal inflammation and bacterial translocation using variations of the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis. We first compared the in vitro ability of LAB to survive gastrointestinal tract (GIT) conditions and their ability to persist in the GIT of mice following daily oral administration. As a control, we included a nonprobiotic Lactobacillus paracasei strain, previously isolated from an endocarditis patient. Feeding high doses of LAB strains to healthy and to TNBS-treated mice did not induce any detrimental effect or abnormal translocation of the bacteria. Oral administration of Lactobacillus salivarius Ls-33 had a significant preventive effect on colitis in mice, while Lactobacillus plantarum Lp-115 and Lactobacillus acidophilus NCFM did not. None of the three selected LAB strains translocated to extraintestinal organs of TNBS-treated mice. In contrast, L. paracasei exacerbated colitis under severe inflammatory conditions and translocated to extraintestinal organs. This study showed that evaluations of the safety and functionality of new probiotics are recommended. We conclude that not all lactobacilli have similar effects on intestinal inflammation and that selected probiotics such as L. salivarius Ls-33 may be considered in the prevention or treatment of intestinal inflammation.

  6. Discovery of a Potent, Selective, and Efficacious Class of Reversible α-Ketoheterocycle Inhibitors of Fatty Acid Amide Hydrolase Effective as Analgesicsa

    OpenAIRE

    Boger, Dale L.; Miyauchi, Hiroshi; Du, Wu; Hardouin, Christophe; Fecik, Robert A.; Cheng, Heng; Hwang, Inkyu; Hedrick, Michael P.; Leung, Donmienne; Acevedo, Orlando; Guimarães, Cristiano R. W.; Jorgensen, William L.; Cravatt, Benjamin F.

    2005-01-01

    Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of reversible FAAH inhibitors that produce analgesia in animal models validating a new therapeutic target for pain intervention. Key to the useful inhibitor discovery was the routi...

  7. Thermally and vibrationally induced conformational isomerizations, infrared spectra, and photochemistry of gallic acid in low-temperature matrices.

    Science.gov (United States)

    Justino, Licínia L G; Reva, Igor; Fausto, Rui

    2016-07-01

    Near-infrared (near-IR) narrowband selective vibrational excitation and annealing of gallic acid (3,4,5-trihydroxybenzoic acid) isolated in cryogenic matrices were used to induce interconversions between its most stable conformers. The isomerizations were probed by infrared spectroscopy. An extensive set of quantum chemical calculations, carried out at the DFT(B3LYP)/6-311++G(d,p) level of approximation, was used to undertake a detailed analysis of the ground state potential energy surface of the molecule. This investigation of the molecule conformational space allowed extracting mechanistic insights into the observed annealing- or near-IR-induced isomerization processes. The infrared spectra of the two most stable conformers of gallic acid in N2, Xe, and Ar matrices were fully assigned. Finally, the UV-induced photochemistry of the matrix isolated compound was investigated. PMID:27394105

  8. Topiramate increases the risk of valproic acid-induced encephalopathy.

    Science.gov (United States)

    Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

    2013-01-01

    Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment.

  9. Mutation-selection models of coding sequence evolution with site-heterogeneous amino acid fitness profiles.

    Science.gov (United States)

    Rodrigue, Nicolas; Philippe, Hervé; Lartillot, Nicolas

    2010-03-01

    Modeling the interplay between mutation and selection at the molecular level is key to evolutionary studies. To this end, codon-based evolutionary models have been proposed as pertinent means of studying long-range evolutionary patterns and are widely used. However, these approaches have not yet consolidated results from amino acid level phylogenetic studies showing that selection acting on proteins displays strong site-specific effects, which translate into heterogeneous amino acid propensities across the columns of alignments; related codon-level studies have instead focused on either modeling a single selective context for all codon columns, or a separate selective context for each codon column, with the former strategy deemed too simplistic and the latter deemed overparameterized. Here, we integrate recent developments in nonparametric statistical approaches to propose a probabilistic model that accounts for the heterogeneity of amino acid fitness profiles across the coding positions of a gene. We apply the model to a dozen real protein-coding gene alignments and find it to produce biologically plausible inferences, for instance, as pertaining to site-specific amino acid constraints, as well as distributions of scaled selection coefficients. In their account of mutational features as well as the heterogeneous regimes of selection at the amino acid level, the modeling approaches studied here can form a backdrop for several extensions, accounting for other selective features, for variable population size, or for subtleties of mutational features, all with parameterizations couched within population-genetic theory. PMID:20176949

  10. Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Piet Habbel; Karsten H Weylandt; Katja Lichopoj; Johannes Nowak; Martin Purschke; Jing-Dong Wang; Cheng-Wei He; Daniel C Baumgart; Jing X Kang

    2009-01-01

    AIM: To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth.METHODS: The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2), p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 (PGE2) generation in the presence of AA and DHA was measured using a PGE2ELISA.RESULTS: AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time- and dosedependent manner. Furthermore, DHA down- regulated mRNA of bcl-2 and up-regulated p21. Interestingly,DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation.DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation, DHA directly reduced PGE2-induced cell proliferation in a dosedependent manner.CONCLUSION: These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2.

  11. Photo-SRM: laser-induced dissociation improves detection selectivity of Selected Reaction Monitoring mode.

    Science.gov (United States)

    Enjalbert, Quentin; Simon, Romain; Salvador, Arnaud; Antoine, Rodolphe; Redon, Sébastien; Ayhan, Mehmet Menaf; Darbour, Florence; Chambert, Stéphane; Bretonnière, Yann; Dugourd, Philippe; Lemoine, Jérôme

    2011-11-30

    Selected Reaction Monitoring (SRM) carried out on triple-quadrupole mass spectrometers coupled to liquid chromatography has been a reference method to develop quantitative analysis of small molecules in biological or environmental matrices for years and is currently emerging as a promising tool in clinical proteomic. However, sensitive assays in complex matrices are often hampered by the presence of co-eluted compounds that share redundant transitions with the target species. On-the-fly better selection of the precursor ion by high-field asymmetric waveform ion mobility spectrometry (FAIMS) or increased quadrupole resolution is one way to escape from interferences. In the present work we document the potential interest of substituting classical gas-collision activation mode by laser-induced dissociation in the visible wavelength range to improve the specificity of the fragmentation step. Optimization of the laser beam pathway across the different quadrupoles to ensure high photo-dissociation yield in Q2 without detectable fragmentation in Q1 was assessed with sucrose tagged with a push-pull chromophore. Next, the proof of concept that photo-SRM ensures more specific detection than does conventional collision-induced dissociation (CID)-based SRM was carried out with oxytocin peptide. Oxytocin was derivatized by the thiol-reactive QSY® 7 C(5)-maleimide quencher on cysteine residues to shift its absorption property into the visible range. Photo-SRM chromatograms of tagged oxytocin spiked in whole human plasma digest showed better detection specificity and sensitivity than CID, that resulted in extended calibration curve linearity. We anticipate that photo-SRM might significantly improve the limit of quantification of classical SRM-based assays targeting cysteine-containing peptides. PMID:22002689

  12. Inflammatory cells′ role in acetic acid-induced colitis

    Directory of Open Access Journals (Sweden)

    Mohammad H Sanei

    2014-01-01

    Full Text Available Background: Free radicals are the known mechanisms responsible for inducing colitis with two origins: Inflammatory cells and tissues. Only the inflammatory cells can be controlled by corticosteroids. Our aim was to assess the importance of neutrophils as one of the inflammatory cells in inducing colitis and to evaluate the efficacy of corticosteroids in the treatment of inflammatory bowel disease (IBD. Materials and Methods: Thirty-six mice were divided into six groups of six mice each. Colitis was induced in three groups by exposing them to acetic acid through enema (group 1, ex vivo (group 3, and enema after immune suppression (group 5. Each group had one control group that was exposed to water injection instead of acetic acid. Tissue samples were evaluated and compared based on macroscopic damages and biochemical and pathological results. Results: Considering neutrophilic infiltration, there were significant differences between groups 1, 3, 5, and the control of group 1. Groups 3, 5, and their controls, and group 1 and the control of group 3 had significant differences in terms of goblet depletion. Based on tissue originated H 2 O 2 , we found significant differences between group 1 and its control and group 3, and also between groups 5 and the control of group 3. All the three groups were significantly different from their controls based on Ferric Reducing Ability of Plasma (FRAP and such differences were also seen between group 1 with two other groups. Conclusion: Neutrophils may not be the only cause of oxidation process in colitis, and also makes the effectiveness of corticosteroids in the treatment of this disease doubtful.

  13. Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain.

    Science.gov (United States)

    Sinha, Mahua; Manna, Prasenjit; Sil, Parames C

    2008-02-01

    Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic-induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free-radical-scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2-diphenyl-1-picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well-established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic-induced oxidative insult in murine brain and is probably due to its antioxidant activity.

  14. Effect of ZSM-5 Acidity on Aromatic Product Selectivity during Upgrading of Pine Pyrolysis Vapors

    Energy Technology Data Exchange (ETDEWEB)

    Engtrakul, Chaiwat; Mukarakate, Calvin; Starace, Anne K.; Magrini, Kimberly A.; Rogers, Allyson K.; Yung, Matthew M.

    2016-07-01

    The impact of catalyst acidity on the selectivity of upgraded biomass pyrolysis products was studied by passing pine pyrolysis vapors over five ZSM-5 catalysts of varying acidity at 500 degrees C. The SiO2-to-Al2O3 ratio (SAR) of the ZSM-5 zeolite was varied from 23 to 280 to control the acidity of the catalyst and the composition of upgraded products. The upgraded product stream was analyzed by GCMS. Additionally, catalysts were characterized using temperature programmed desorption, diffuse-reflectance FTIR spectroscopy, N2 physisorption, and X-ray diffraction. The results showed that the biomass pyrolysis vapors were highly deoxygenated to form a slate of aromatic hydrocarbons over all of the tested ZSM-5 catalysts. As the overall acidity of the ZSM-5 increased the selectivity toward alkylated (substituted) aromatics (e.g., xylene, dimethyl-naphthalene, and methyl-anthracene) decreased while the selectivity toward unsubstituted aromatics (e.g., benzene, naphthalene, and anthracene) increased. Additionally, the selectivity toward polycyclic aromatic compounds (2-ring and 3-ring) increased as catalyst acidity increased, corresponding to a decrease in acid site spacing. The increased selectivity toward less substituted polycyclic aromatic compounds with increasing acidity is related to the relative rates of cyclization and alkylation reactions within the zeolite structure. As the acid site concentration increases and sites become closer to each other, the formation of additional cyclization products occurs at a greater rate than alkylated products. The ability to adjust product selectivity within 1-, 2-, and 3-ring aromatic families, as well as the degree of substitution, by varying ZSM-5 acidity could have significant benefits in terms creating a slate of upgraded biomass pyrolysis products to meet specific target market demands.

  15. Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Jankovic-Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan

    2012-01-01

    Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

  16. Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Pavle Randjelovic

    2012-01-01

    Full Text Available Gentamicin (GM is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

  17. Selective adsorption of L- and D-amino acids on calcite: Implications for biochemical homochirality

    Science.gov (United States)

    Hazen, R. M.; Filley, T. R.; Goodfriend, G. A.

    2001-01-01

    The emergence of biochemical homochirality was a key step in the origin of life, yet prebiotic mechanisms for chiral separation are not well constrained. Here we demonstrate a geochemically plausible scenario for chiral separation of amino acids by adsorption on mineral surfaces. Crystals of the common rock-forming mineral calcite (CaCO(3)), when immersed in a racemic aspartic acid solution, display significant adsorption and chiral selectivity of d- and l-enantiomers on pairs of mirror-related crystal-growth surfaces. This selective adsorption is greater on crystals with terraced surface textures, which indicates that d- and l-aspartic acid concentrate along step-like linear growth features. Thus, selective adsorption of linear arrays of d- and l-amino acids on calcite, with subsequent condensation polymerization, represents a plausible geochemical mechanism for the production of homochiral polypeptides on the prebiotic Earth.

  18. Selective Acidic Leaching of Spent Zinc-Carbon Batteries Followed by Zinc Electrowinning

    Science.gov (United States)

    Shalchian, Hossein; Rafsanjani-Abbasi, Ali; Vahdati-Khaki, Jalil; Babakhani, Abolfazl

    2015-02-01

    In this work, a selective acidic leaching procedure was employed for recycling zinc from spent zinc-carbon batteries. Leaching experiments were carried out in order to maximize zinc recovery and minimize manganese recovery in diluted sulfuric acid media. Response surface methodology and analysis of variance were employed for experimental design, data analysis, and leaching optimization. The experimental design has 28 experiments that include 24 main runs and four replicate in center point. The optimal conditions obtained from the selective acidic leaching experiments, were sulfuric acid concentration of 1 pct v/v, leaching temperature of 343 K (70 °C), pulp density of 8 pct w/v, and stirring speed of 300 rpm. The results show that the zinc and manganese recoveries after staged selective leaching are about 92 and 15 pct, respectively. Finally, metallic zinc with purity of 99.9 pct and electrolytic manganese dioxide were obtained by electrowinning.

  19. Synthesis selective transport properties of cleft-type ionophores having two convergent hydroxamic acid functions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Duck Hee; Choi, Mi Jung; Chang, Suk Kyu [Chungang Univ., Seoul (Korea, Republic of)

    2001-07-01

    A series of cleft-type ionophores having two convergent hydroxamic acid functions are prepared and their selective ionophoric properties toward heavy metal and transition metal ions have been investigated. Hydroxamic acids 3 exhibited a prominent selectivity toward heavy metal ions of Hg{sup 2+} and Pb{sup 2+} , and transition metal ions of Cu{sup 2+} over other transition metal and alkaline earth metal ions from slightly acidic source phase (pH 6) to an acidic receiving phase (pH 1). Selective ionophoric properties toward Pb{sup 2+} and Cu{sup 2+} ions over other surveyed metal ions are also confirmed by the FAB-MS measurements.

  20. Fatty acid specificity of hormone-sensitive lipase. Implication in the selective hydrolysis of triacylglycerols.

    Science.gov (United States)

    Raclot, T; Holm, C; Langin, D

    2001-12-01

    The selective mobilization of fatty acids from white fat cells depends on their molecular structure, in particular the degree of unsaturation. The present study was designed to examine if the release of fatty acids by hormone-sensitive lipase (HSL) in vitro i) is influenced by the amount of unsaturation, ii) depends on the temperature, and iii) could explain the selective pattern of fatty acid mobilization and notably the preferential mobilization of certain highly unsaturated fatty acids. Recombinant rat and human HSL were incubated with a lipid emulsion. The hydrolysis of 35 individual fatty acids, ranging in chain length from 12 to 24 carbon atoms and in unsaturation from 0 to 6 double bonds was measured. Fatty acid composition of in vitro released NEFA was compared with that of fat cell triacylglycerols (TAG), the ratio % NEFA/% TAG being defined as the relative hydrolysis. The relative hydrolysis of individual fatty acids differed widely, ranging from 0.44 (24:1n-9) to 1.49 (18:1n-7) with rat HSL, and from 0.38 (24:1n-9) to 1.67 (18:1n-7) with human HSL. No major difference was observed between rat and human HSL. The relative release was dependent on the number of double bonds according to chain length. The amount of fatty acid released by recombinant rat HSL was decreased but remained robust at 4 degrees C compared with 37 degrees C, and the relative hydrolysis of some individual fatty acids was affected. The relative hydrolysis of fatty acids moderately, weakly, and highly mobilized by adipose tissue in vivo was similar and close to unity in vitro. We conclude that i) the release of fatty acids by HSL is only slightly affected by their degree of unsaturation, ii) the ability of HSL to efficiently and selectively release fatty acids at low temperature could reflect a cold adaptability for poikilotherms or hibernators when endogenous lipids are needed, and iii) the selectivity of fatty acid hydrolysis by HSL does not fully account for the selective pattern of

  1. In vitro colonic metabolism of coffee and chlorogenic acid results in selective changes in human faecal microbiota growth.

    Science.gov (United States)

    Mills, Charlotte E; Tzounis, Xenofon; Oruna-Concha, Maria-Jose; Mottram, Don S; Gibson, Glenn R; Spencer, Jeremy P E

    2015-04-28

    Coffee is a relatively rich source of chlorogenic acids (CGA), which, as other polyphenols, have been postulated to exert preventive effects against CVD and type 2 diabetes. As a considerable proportion of ingested CGA reaches the large intestine, CGA may be capable of exerting beneficial effects in the large gut. Here, we utilise a stirred, anaerobic, pH-controlled, batch culture fermentation model of the distal region of the colon in order to investigate the impact of coffee and CGA on the growth of the human faecal microbiota. Incubation of coffee samples with the human faecal microbiota led to the rapid metabolism of CGA (4 h) and the production of dihydrocaffeic acid and dihydroferulic acid, while caffeine remained unmetabolised. The coffee with the highest levels of CGA (Pcoffees) induced a significant increase in the growth of Bifidobacterium spp. relative to the control vessel at 10 h after exposure (Pcoffee) induced a significant increase in the growth of Bifidobacterium spp. (P<0·05). CGA alone also induced a significant increase in the growth of the Clostridium coccoides-Eubacterium rectale group (P<0·05). This selective metabolism and subsequent amplification of specific bacterial populations could be beneficial to host health.

  2. Selective inhibition of type 2 fatty acid synthetase by the antibiotic thiolactomycin

    Energy Technology Data Exchange (ETDEWEB)

    Nishida, Ikuo; Kawaguchi, Akihiko; Yamada, Mitsuhiro (Tokyo Univ. (Japan). Faculty of Science)

    1984-03-01

    The antibiotic thiolactomycin inhibits the fatty acid synthesis from both (1-/sup 14/C)-acetate and (2/sup 14/C) malonyl-CoA of spinach leaves, developing castor bean endosperms and avocado mesocarp. On the other hand, fatty acid synthetases of Brevibacterium ammoniagenes and Corynebacterium glutamicum are much less sensitive to this antibiotic. As Hayashi et al. have indicated in their paper that thiolactomycin inhibits fatty acid synthetase of Escherichia coli but has little effect on the synthetases of yeast and rat liver, thiolactomycin is suggested to be a selective inhibitor of type 2 fatty acid synthetases.

  3. Selective inhibition of type 2 fatty acid synthetase by the antibiotic thiolactomycin

    International Nuclear Information System (INIS)

    The antibiotic thiolactomycin inhibits the fatty acid synthesis from both [1-14C]-acetate and [214C] malonyl-CoA of spinach leaves, developing castor bean endosperms and avocado mesocarp. On the other hand, fatty acid synthetases of Brevibacterium ammoniagenes and Corynebacterium glutamicum are much less sensitive to this antibiotic. As Hayashi et al. have indicated in their paper that thiolactomycin inhibits fatty acid synthetase of Escherichia coli but has little effect on the synthetases of yeast and rat liver, thiolactomycin is suggested to be a selective inhibitor of type 2 fatty acid synthetases. (author)

  4. Enhancing aptamer function and stability via in vitro selection using modified nucleic acids.

    Science.gov (United States)

    Meek, Kirsten N; Rangel, Alexandra E; Heemstra, Jennifer M

    2016-08-15

    Nucleic acid aptamers have emerged as a promising alternative to antibodies for use as recognition elements in therapeutics, bioimaging, and analytical applications. A key benefit that aptamers possess relative to antibodies is their ability to be chemically synthesized. This advantage, coupled with the broad range of modified nucleotide building blocks that can be constructed using chemical synthesis, has enabled the discovery and development of modified aptamers having extraordinary affinity, specificity, and biostability. Early efforts to generate modified aptamers focused on selection of a native DNA or RNA aptamer, followed by post-selection trial-and-error testing of modifications. However, recent advances in polymerase engineering and templated nucleic acid synthesis have enabled the direct selection of aptamers having modified backbones and nucleobases. This review will discuss these technological advances and highlight the improvements in aptamer function that have been realized through in vitro selection of non-natural nucleic acids. PMID:27012179

  5. Salicylic acid induces mitochondrial injury by inhibiting ferrochelatase heme biosynthesis activity.

    Science.gov (United States)

    Gupta, Vipul; Liu, Shujie; Ando, Hideki; Ishii, Ryohei; Tateno, Shumpei; Kaneko, Yuki; Yugami, Masato; Sakamoto, Satoshi; Yamaguchi, Yuki; Nureki, Osamu; Handa, Hiroshi

    2013-12-01

    Salicylic acid is a classic nonsteroidal anti-inflammatory drug. Although salicylic acid also induces mitochondrial injury, the mechanism of its antimitochondrial activity is not well understood. In this study, by using a one-step affinity purification scheme with salicylic acid-immobilized beads, ferrochelatase (FECH), a homodimeric enzyme involved in heme biosynthesis in mitochondria, was identified as a new molecular target of salicylic acid. Moreover, the cocrystal structure of the FECH-salicylic acid complex was determined. Structural and biochemical studies showed that salicylic acid binds to the dimer interface of FECH in two possible orientations and inhibits its enzymatic activity. Mutational analysis confirmed that Trp301 and Leu311, hydrophobic amino acid residues located at the dimer interface, are directly involved in salicylic acid binding. On a gel filtration column, salicylic acid caused a shift in the elution profile of FECH, indicating that its conformational change is induced by salicylic acid binding. In cultured human cells, salicylic acid treatment or FECH knockdown inhibited heme synthesis, whereas salicylic acid did not exert its inhibitory effect in FECH knockdown cells. Concordantly, salicylic acid treatment or FECH knockdown inhibited heme synthesis in zebrafish embryos. Strikingly, the salicylic acid-induced effect in zebrafish was partially rescued by FECH overexpression. Taken together, these findings illustrate that FECH is responsible for salicylic acid-induced inhibition of heme synthesis, which may contribute to its antimitochondrial and anti-inflammatory function. This study establishes a novel aspect of the complex pharmacological effects of salicylic acid.

  6. 2-Benzazolyl-4-Piperazin-1-Ylsulfonylbenzenecarbohydroxamic Acids as Novel Selective Histone Deacetylase-6 Inhibitors with Antiproliferative Activity.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available We have screened our compound collection in an established cell based assay that measures the derepression of an epigenetically silenced transgene, the locus derepression assay. The screen led to the identification of 4-[4-(1-methylbenzimidazol-2-ylpiperazin-1-yl]sulfonylbenzenecarbohydroxamic acid (9b as an active which was found to inhibit HDAC1. In initial structure activity relationships study, the 1-methylbenzimidazole ring was replaced by the isosteric heterocycles benzimidazole, benzoxazole, and benzothiazole and the position of the hydroxamic acid substituent on the phenyl ring was varied. Whereas compounds bearing a para substituted hydroxamic acid (9a-d were active HDAC inhibitors, the meta substituted analogues (8a-d were appreciably inactive. Compounds 9a-d selectively inhibited HDAC6 (IC50 = 0.1-1.0 μM over HDAC1 (IC50 = 0.9-6 μM and moreover, also selectively inhibited the growth of lung cancer cells vs. patient matched normal cells. The compounds induce a cell cycle arrest in the S-phase while induction of apoptosis is neglible as compared to controls. Molecular modeling studies uncovered that the MM-GBSA energy for interaction of 9a-d with HDAC6 was higher than for HDAC1 providing structural rationale for the HDAC6 selectivity.

  7. 2-Benzazolyl-4-Piperazin-1-Ylsulfonylbenzenecarbohydroxamic Acids as Novel Selective Histone Deacetylase-6 Inhibitors with Antiproliferative Activity

    Science.gov (United States)

    Wang, Lei; Kofler, Marina; Brosch, Gerald; Melesina, Jelena; Sippl, Wolfgang; Martinez, Elisabeth D.; Easmon, Johnny

    2015-01-01

    We have screened our compound collection in an established cell based assay that measures the derepression of an epigenetically silenced transgene, the locus derepression assay. The screen led to the identification of 4-[4-(1-methylbenzimidazol-2-yl)piperazin-1-yl]sulfonylbenzenecarbohydroxamic acid (9b) as an active which was found to inhibit HDAC1. In initial structure activity relationships study, the 1-methylbenzimidazole ring was replaced by the isosteric heterocycles benzimidazole, benzoxazole, and benzothiazole and the position of the hydroxamic acid substituent on the phenyl ring was varied. Whereas compounds bearing a para substituted hydroxamic acid (9a-d) were active HDAC inhibitors, the meta substituted analogues (8a-d) were appreciably inactive. Compounds 9a-d selectively inhibited HDAC6 (IC50 = 0.1–1.0μM) over HDAC1 (IC50 = 0.9–6μM) and moreover, also selectively inhibited the growth of lung cancer cells vs. patient matched normal cells. The compounds induce a cell cycle arrest in the S-phase while induction of apoptosis is neglible as compared to controls. Molecular modeling studies uncovered that the MM-GBSA energy for interaction of 9a-d with HDAC6 was higher than for HDAC1 providing structural rationale for the HDAC6 selectivity. PMID:26698121

  8. D-amino acid-induced expression of D-amino acid oxidase in the yeast Schizosaccharomyces pombe.

    Science.gov (United States)

    Takahashi, Shouji; Okada, Hirotsune; Abe, Katsumasa; Kera, Yoshio

    2012-12-01

    We investigated D-amino acid oxidase (DAO) induction in the popular model yeast Schizosaccharomyces pombe. The product of the putative DAO gene of the yeast expressed in E. coli displayed oxidase activity to neutral and basic D-amino acids, but not to an L-amino acid or acidic D-amino acids, showing that the putative DAO gene encodes catalytically active DAO. DAO activity was weakly detected in yeast cells grown on a culture medium without D-amino acid, and was approximately doubled by adding D-alanine. The elimination of ammonium chloride from culture medium induced activity by up to eight-fold. L-Alanine also induced the activity, but only by about half of that induced by D-alanine. The induction by D-alanine reached a maximum level at 2 h cultivation; it remained roughly constant until cell growth reached a stationary phase. The best inducer was D-alanine, followed by D-proline and then D-serine. Not effective were N-carbamoyl-D,L-alanine (a better inducer of DAO than D-alanine in the yeast Trigonopsis variabilis), and both basic and acidic D-amino acids. These results showed that S. pombe DAO could be a suitable model for analyzing the regulation of DAO expression in eukaryotic organisms. PMID:22986818

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

    Science.gov (United States)

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

    1997-01-01

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

  10. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity.

    Directory of Open Access Journals (Sweden)

    Esther M Verhaag

    Full Text Available Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis.To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions.HepG2.rNtcp cells were preconditioned (24 h with sub-apoptotic concentrations (0.1-50 μM of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h, menadione (50 μM, 6 h or cytokine mixture (CM; 6 h. Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11 and bile acid sensors, as well as intracellular GCDCA levels were analyzed.Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauroursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid preconditioning did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, preconditioning with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA preconditioning specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA preconditioning was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- preconditioning enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA

  11. Retinoic acid-induced gene expression in normal and leukemic myeloid cells

    OpenAIRE

    1986-01-01

    Retinoic acid has been shown to induce large accumulations of tissue transglutaminase in cultured myeloid cells. Addition of retinoic acid to mouse resident peritoneal macrophages increased the level of tissue transglutaminase mRNA within 30-60 min. Retinoic acid also increased tissue transglutaminase mRNA levels in human promyelocytic leukemia (HL- 60) cells. These studies show that retinoic acid can induce acute alterations in specific gene expression in both normal and leukemic myeloid cells.

  12. Clavulanic acid inhibits MPP+-induced ROS generation and subsequent loss of dopaminergic cells☆

    OpenAIRE

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2012-01-01

    Clavulanic acid is a psychoactive compound that has been shown to modulate central nervous system activity. Importantly, in neurotoxin-induced animal models, clavulanic acid has been shown to improve motor function (Huh et al., 2010) suggesting that it can be neuroprotective; however, the mechanism as how clavulanic acid can induce neuroprotection is not known. We demonstrate here that clavulanic acid abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) which mimics Park...

  13. A comparative proteomic analysis of the simple amino acid repeat distributions in Plasmodia reveals lineage specific amino acid selection.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available BACKGROUND: Microsatellites have been used extensively in the field of comparative genomics. By studying microsatellites in coding regions we have a simple model of how genotypic changes undergo selection as they are directly expressed in the phenotype as altered proteins. The simplest of these tandem repeats in coding regions are the tri-nucleotide repeats which produce a repeat of a single amino acid when translated into proteins. Tri-nucleotide repeats are often disease associated, and are also known to be unstable to both expansion and contraction. This makes them sensitive markers for studying proteome evolution, in closely related species. RESULTS: The evolutionary history of the family of malarial causing parasites Plasmodia is complex because of the life-cycle of the organism, where it interacts with a number of different hosts and goes through a series of tissue specific stages. This study shows that the divergence between the primate and rodent malarial parasites has resulted in a lineage specific change in the simple amino acid repeat distribution that is correlated to A-T content. The paper also shows that this altered use of amino acids in SAARs is consistent with the repeat distributions being under selective pressure. CONCLUSIONS: The study shows that simple amino acid repeat distributions can be used to group related species and to examine their phylogenetic relationships. This study also shows that an outgroup species with a similar A-T content can be distinguished based only on the amino acid usage in repeats, and suggest that this might be a useful feature for proteome clustering. The lineage specific use of amino acids in repeat regions suggests that comparative studies of SAAR distributions between proteomes gives an insight into the mechanisms of expansion and the selective pressures acting on the organism.

  14. Effect of Ascorbic Acid on Lipid Peroxidation Induced by Ceftazidime

    Directory of Open Access Journals (Sweden)

    Devbhuti P*,1

    2011-01-01

    Full Text Available Lipid peroxidation is the oxidative deterioration of polyunsaturated lipids which is a free radical related process and responsible for thedevelopment of many diseases and disorders like diabetes mellitus, hypertension, cancer etc. End products of lipid peroxidation aremalondialdehyde (MDA, 4-hydroxy-2-nonenal (4-HNE, etc. which are the ultimate mediator of toxicity. Antioxidants have the capability toinhibit lipid peroxidation. Keeping in mind this fact, the present in vitro study was carried out to evaluate lipid peroxidation induction potential of ceftazidime, a cephalosporin antibiotic and its suppression with ascorbic acid considering some laboratory markers of lipid peroxidation like MDA, 4-HNE and reduced glutathione (GSH. Goat liver was used as the lipid source. After treatment of the liver homogenate with drug and/or antioxidant the levels of 4-HNE, MDA and GSH were estimated in different samples at different hours of incubation. The results showed that the drug ceftazidime could significantly induce lipid peroxidation and the antioxidant ascorbic acid has the capability to inhibit ceftazidime-inducedlipid peroxidation.

  15. Iron transformations induced by an acid-tolerant Desulfosporosinus species.

    Science.gov (United States)

    Bertel, Doug; Peck, John; Quick, Thomas J; Senko, John M

    2012-01-01

    The mineralogical transformations of Fe phases induced by an acid-tolerant, Fe(III)- and sulfate-reducing bacterium, Desulfosporosinus sp. strain GBSRB4.2 were evaluated under geochemical conditions associated with acid mine drainage-impacted systems (i.e., low pH and high Fe concentrations). X-ray powder diffractometry coupled with magnetic analysis by first-order reversal curve diagrams were used to evaluate mineral phases produced by GBSRB4.2 in media containing different ratios of Fe(II) and Fe(III). In medium containing Fe predominately in the +II oxidation state, ferrimagnetic, single-domain greigite (Fe₃S₄) was formed, but the addition of Fe(III) inhibited greigite formation. In media that contained abundant Fe(III) [as schwertmannite; Fe₈O₈(OH)₆SO₄ · nH₂O], the activities of strain GBSRB4.2 enhanced the transformation of schwertmannite to goethite (α-FeOOH), due to the increased pH and Fe(II) concentrations that resulted from the activities of GBSRB4.2. PMID:22038606

  16. Analysis of Salicylic Acid Induced Proteins in Rice

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    An analysis using SDS-PAGE of acidic and basic protein fractions extracted from rice seedling treated with salicylic acid (SA) yielded several new proteins, some of which are similar in relative molecular mass to PR-1a,c, PR-2, 2e and PR-3d, 3e of tobacco.Direct assays for peroxidases and β-1,3-glucanases demonstrated that the activities of the two enzymes in the rice seedlings increased rapidly with time after SA treatment, reaching a maximum 6 days after treatment.Disease resistance tests showed that SA treated rice seedlings stunted the development of blight lesions and displayed higher resistance to rice blight pathogen (Xanthomonas oryzea pv.oryzea).The data suggest that the treatment with SA, even for plants with high endogenous SA levels such as rice, may induce the appearance of new proteins and the formation of disease resistance.The results contribute to the analysis of the SA role in rice systemic acquired resistance.

  17. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

    Directory of Open Access Journals (Sweden)

    Pernilla Lång

    Full Text Available BACKGROUND: Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer. PRINCIPAL FINDINGS: Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity. CONCLUSION: Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  18. Temperature Induced Aggregation and Clouding in Humic Acid Solutions

    Directory of Open Access Journals (Sweden)

    Leah Shaffer

    2015-01-01

    Full Text Available Humic acids in aqueous solution demonstrate inverse temperature-solubility relationships when solution conditions are manipulated to reduce coulombic repulsion among the humic polyanions. These effects were followed by dynamic light scattering (DLS measurements of the resulting aggregates, as well as the addition of a polarity sensitive fluorescent probe (pyrene. The humic solutions could be primed for temperature induced clouding by carefully lowering the pH to a point where hydration effects became dominant. The exact value of the cloud point (CP was a function of both pH and humate concentration. The CPs mostly lay in the range 50–90°C, but DLS showed that temperature induced aggregation proceeded from approximately 30°C onward. Similar effects could be achieved by adding multivalent cations at concentrations below those which cause spontaneous precipitation. The declouding of clouded humate solutions could be affected by lowering the temperature combined with mechanical agitation to disentangle the humic polymers.

  19. Acetic acid bacteria in traditional balsamic vinegar: phenotypic traits relevant for starter cultures selection.

    Science.gov (United States)

    Gullo, Maria; Giudici, Paolo

    2008-06-30

    This review focuses on acetic acid bacteria in traditional balsamic vinegar process. Although several studies are available on acetic acid bacteria ecology, metabolism and nutritional requirements, their activity as well as their technological traits in homemade vinegars as traditional balsamic vinegar is not well known. The basic technology to oxidise cooked grape must to produce traditional balsamic vinegar is performed by the so called "seed-vinegar" that is a microbiologically undefined starter culture obtained from spontaneous acetification of previous raw material. Selected starter cultures are the main technological improvement in order to innovate traditional balsamic vinegar production but until now they are rarely applied. To develop acetic acid bacteria starter cultures, selection criteria have to take in account composition of raw material, acetic acid bacteria metabolic activities, applied technology and desired characteristics of the final product. For traditional balsamic vinegar, significative phenotypical traits of acetic acid bacteria have been highlighted. Basic traits are: ethanol preferred and efficient oxidation, fast rate of acetic acid production, tolerance to high concentration of acetic acid, no overoxidation and low pH resistance. Specific traits are tolerance to high sugar concentration and to a wide temperature range. Gluconacetobacter europaeus and Acetobacter malorum strains can be evaluated to develop selected starter cultures since they show one or more suitable characters. PMID:18177968

  20. Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

    Directory of Open Access Journals (Sweden)

    Magd A. Kotb

    2012-07-01

    Full Text Available Ursodeoxycholic acid (UDCA is a steroid bile acid approved for primary biliary cirrhosis (PBC. UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively. “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day and toxic dose (28 mg/kg/day, and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

  1. Amino acid selective unlabeling for sequence specific resonance assignments in proteins

    Energy Technology Data Exchange (ETDEWEB)

    Krishnarjuna, B.; Jaipuria, Garima; Thakur, Anushikha [Indian Institute of Science, NMR Research Centre (India); D' Silva, Patrick, E-mail: patrick@biochem.iisc.ernet.in [Indian Institute of Science, Department of Biochemistry (India); Atreya, Hanudatta S., E-mail: hsatreya@sif.iisc.ernet.in [Indian Institute of Science, NMR Research Centre (India)

    2011-01-15

    Sequence specific resonance assignment constitutes an important step towards high-resolution structure determination of proteins by NMR and is aided by selective identification and assignment of amino acid types. The traditional approach to selective labeling yields only the chemical shifts of the particular amino acid being selected and does not help in establishing a link between adjacent residues along the polypeptide chain, which is important for sequential assignments. An alternative approach is the method of amino acid selective 'unlabeling' or reverse labeling, which involves selective unlabeling of specific amino acid types against a uniformly {sup 13}C/{sup 15}N labeled background. Based on this method, we present a novel approach for sequential assignments in proteins. The method involves a new NMR experiment named, {l_brace}{sup 12}CO{sub i}-{sup 15}N{sub i+1}{r_brace}-filtered HSQC, which aids in linking the {sup 1}H{sup N}/{sup 15}N resonances of the selectively unlabeled residue, i, and its C-terminal neighbor, i + 1, in HN-detected double and triple resonance spectra. This leads to the assignment of a tri-peptide segment from the knowledge of the amino acid types of residues: i - 1, i and i + 1, thereby speeding up the sequential assignment process. The method has the advantage of being relatively inexpensive, applicable to {sup 2}H labeled protein and can be coupled with cell-free synthesis and/or automated assignment approaches. A detailed survey involving unlabeling of different amino acid types individually or in pairs reveals that the proposed approach is also robust to misincorporation of {sup 14}N at undesired sites. Taken together, this study represents the first application of selective unlabeling for sequence specific resonance assignments and opens up new avenues to using this methodology in protein structural studies.

  2. Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

    Science.gov (United States)

    Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

    2003-01-01

    Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery. Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells. To assess the role of calcium in the DHA-induced acidification, we conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+) buffer. We observed that there was no difference in the degree of DHA-induced transient acidification in both the experimental conditions, though pHi recovery was faster in 0% Ca2+ medium than that in 100% Ca2+ medium. In the presence of BAPTA, a calcium chelator, a rapid recovery of DHA-induced acidosis was observed. Furthermore, addition of CaCl2 into 0% Ca2+ medium curtailed DHA-evoked rapid pHi recovery. In 0% Ca2+ medium, containing BAPTA, DHA did not evoke increases in [Ca2+]i, though this fatty acid still induced a rapid acidification in these cells. These observations suggest that calcium is implicated in the long-lasting DHA-induced acidosis. DHA-induced rapid acidification may be due to its deprotonation in the plasma membrane (flip-flop model), as suggested by the following observations: (1) DHA with a –COOH group induced intracellular acidification, but this fatty acid with a –COOCH3 group failed to do so, and (2) DHA, but not propionic acid, -induced acidification was completely reversed by addition of fatty acid-free bovine serum albumin in these cells. These results suggest that DHA induces acidosis via deprotonation and Ca2+ mobilization in human T-cells. PMID:14645139

  3. Selective agonists of retinoic acid receptors: comparative toxicokinetics and embryonic exposure.

    Science.gov (United States)

    Arafa, H M; Elmazar, M M; Hamada, F M; Reichert, U; Shroot, B; Nau, H

    2000-01-01

    Three biologically active synthetic retinoids were investigated that bind selectively to retinoic acid receptors RARs (alpha, beta and gamma). The retinoids were previously demonstrated to have different teratogenic effects in the mouse in terms of potency and regioselectivity. The teratogenic potency rank order (alpha >beta >gamma) was found to be more or less compatible with the receptor binding affinities and transactivation potencies of the retinoid ligands to their respective receptors. The RARalpha agonist (Am580; CD336) induced a wide spectrum of malformations; CD2019 (RARbeta agonist) and especially CD437 (RARgamma agonist) produced more restricted defects. In the current study we tried to address whether the differences in teratogenic effects are solely related to binding affinity and transactivation differences or also due to differences in embryonic exposure. Therefore, transplacental kinetics of the ligands were assessed following administration of a single oral dose of 15 mg/kg of either retinoid given to NMRI mice on day 11 of gestation. Am580 was rapidly transferred to the embryo resulting in the highest embryonic exposure [embryo to maternal plasma area under the time vs concentration curve (AUC)(0-24 h )ratio (E/M) was 1.7], in accordance with its highest teratogenic potency. The low placental transfer of CD2019 (E/M of 0.3) was compatible with its lower teratogenic potential. Of major interest was the finding that the CD437, though being least teratogenic, exhibited considerable embryonic exposure (E/M of 0.6). These findings suggest that both the embryonic exposure and receptor binding transactivation selectivity are crucial determinants of the teratogenicity of these retinoid ligands.

  4. Mechanochemical approach for selective deactivation of external surface acidity of ZSM-5 zeolite catalyst.

    Science.gov (United States)

    Inagaki, Satoshi; Sato, Koki; Hayashi, Shunsuke; Tatami, Junichi; Kubota, Yoshihiro; Wakihara, Toru

    2015-03-01

    The acid sites associated with the external surface of zeolite particles are responsible for undesirable consecutive reactions, such as isomerization, alkylation, and oligomerization, resulting in a lower selectivity to a target product; therefore, the selective modification (deactivation) of the external surface of zeolite particles has been an important issue in zeolite science. Here, a new method for surface deactivation of zeolite catalyst was tested via a mechanochemical approach using powder composer. Postsynthetic mechanochemical treatment of ZSM-5 zeolite causes a selective deactivation of catalytically active sites existing only on the external surface, as a potentially useful catalyst for highly selective production of p-xylene. PMID:25654542

  5. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats.

    Science.gov (United States)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa; Adam, Klaus-Peter; Alexander, Danny C; Lawton, Kay A; Milburn, Michael V; Ryals, John A; Wulff, Jacob E; Guo, Lining

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. PMID:23360887

  6. Clavulanic acid inhibits MPP+-induced ROS generation and subsequent loss of dopaminergic cells☆

    Science.gov (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B.

    2013-01-01

    Clavulanic acid is a psychoactive compound that has been shown to modulate central nervous system activity. Importantly, in neurotoxin-induced animal models, clavulanic acid has been shown to improve motor function (Huh et al., 2010) suggesting that it can be neuroprotective; however, the mechanism as how clavulanic acid can induce neuroprotection is not known. We demonstrate here that clavulanic acid abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) which mimics Parkinson’s disease (PD) by inducing neurodegeneration. To further establish the mechanism we identified that clavulanic acid inhibits neurotoxin-induced loss of mitochondrial membrane potential and ROS production. Consistent with these results, neurotoxin-induced increase in Bax levels was also decreased in clavulanic acid treated cells. Importantly, neurotoxin-induced release of cytochrome c levels as well as caspase activation was also inhibited in clavulanic acid treated cells. In addition, Bcl-xl levels were also restored and the Bcl-xl/Bax ratio that is critical for inducing apoptosis was increased in clavulanic acid treated cells. Overall, these results suggest that clavulanic acid is intimately involved in inhibiting neurotoxin-induced loss of mitochondrial function and induction of apoptosis that contributes towards neuronal survival. PMID:22750587

  7. Clavulanic acid inhibits MPP⁺-induced ROS generation and subsequent loss of dopaminergic cells.

    Science.gov (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2012-08-21

    Clavulanic acid is a psychoactive compound that has been shown to modulate central nervous system activity. Importantly, in neurotoxin-induced animal models, clavulanic acid has been shown to improve motor function (Huh et al., 2010) suggesting that it can be neuroprotective; however, the mechanism as how clavulanic acid can induce neuroprotection is not known. We demonstrate here that clavulanic acid abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) which mimics Parkinson's disease (PD) by inducing neurodegeneration. To further establish the mechanism we identified that clavulanic acid inhibits neurotoxin-induced loss of mitochondrial membrane potential and ROS production. Consistent with these results, neurotoxin-induced increase in Bax levels was also decreased in clavulanic acid treated cells. Importantly, neurotoxin-induced release of cytochrome c levels as well as caspase activation was also inhibited in clavulanic acid treated cells. In addition, Bcl-xl levels were also restored and the Bcl-xl/Bax ratio that is critical for inducing apoptosis was increased in clavulanic acid treated cells. Overall, these results suggest that clavulanic acid is intimately involved in inhibiting neurotoxin-induced loss of mitochondrial function and induction of apoptosis that contributes towards neuronal survival.

  8. A selective voltammetric detection for dopamine using poly(gallic acid) film modified electrode

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The electrochemistry behavior of dopamine was investigated by cyclic voltammetry and differential pulse voltammetry at a poly (gallic acid) film modified glassy carbon electrode.Two electrons and two protons participated in the diffusion-controlled electrocatalytic oxidation of dopamine with a diffusion coefficient of 2.186×10~(-5) cm~2/s.The interference of ascorbic acid with the determination of dopamine could be efficiently eliminated.This work provided a simple approach to selectively and sensitively...

  9. Selection of potential probiotic lactic acid bacteria from fermented olives by in vitro tests

    OpenAIRE

    Argyri, Anthoula; Zoumpopoulou, Georgia; Karatzas, Kimon Andreas; Tsakalidou, Effie; Nychas, George John; Panagou, Efstathios; Tassou, Chrysoula

    2012-01-01

    The present study aims to evaluate the probiotic potential of lactic acid bacteria (LAB) isolated from naturally fermented olives and select candidates to be used as probiotic starters for the improvement of the traditional fermentation process and the production of newly added value functional foods. Seventy one (71) lactic acid bacterial strains (17 Leuconostoc mesenteroides, 1 Ln. pseudomesenteroides, 13 Lactobacillus plantarum, 37 Lb. pentosus, 1 Lb. paraplantarum, and 2 Lb. paracasei sub...

  10. The Role of Fatty Acids and Caveolin-1 in TNF-α-Induced Endothelial Cell Activation

    OpenAIRE

    Wang, Lei; Lim, Eun-Jin; Toborek, Michal; Hennig, Bernhard

    2008-01-01

    Hypertriglyceridemia and associated high circulating free fatty acids are important risk factors of atherosclerosis. In contrast to omega-3 fatty acids, linoleic acid, the major omega-6 unsaturated fatty acid in the American diet, may be atherogenic by amplifying an endothelial inflammatory response. We hypothesize that omega-6 and omega-3 fatty acids can differentially modulate TNF-α-induced endothelial cell activation and that functional plasma membrane microdomains called caveolae are requ...

  11. Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

    International Nuclear Information System (INIS)

    There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

  12. 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 ...

  13. Punicic acid a conjugated linolenic acid inhibits TNFalpha-induced neutrophil hyperactivation and protects from experimental colon inflammation in rats.

    Directory of Open Access Journals (Sweden)

    Tarek Boussetta

    Full Text Available BACKGROUND: Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO. The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation. CONCLUSIONS/SIGNIFICANCE: These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases.

  14. Mechanism of angiotensin II-induced arachidonic acid metabolite release in aortic smooth muscle cells: involvement of phospholipase D.

    Science.gov (United States)

    Shinoda, J; Kozawa, O; Suzuki, A; Watanabe-Tomita, Y; Oiso, Y; Uematsu, T

    1997-02-01

    In a previous study, we have shown that angiotensin II (Ang II) activates phosphatidylcholine-hydrolyzing phospholipase D due to Ang II-induced Ca2+ influx from extracellular space in subcultured rat aortic smooth muscle cells. In the present study, we have investigated the role of phospholipase D in Ang II-induced arachidonic acid (AA) metabolite release and prostacyclin synthesis in subcultured rat aortic smooth muscle cells. Ang II significantly stimulated AA metabolite release in a concentration-dependent manner in the range between 1 nmol/I and 0.1 mumol/I. D.L.-Propranolol hydrochloride (propranolol), an inhibitor of phosphatidic acid phosphohydrolase, significantly inhibited the Ang II-induced release of AA metabolites. The Ang II-induced AA metabolite release was reduced by chelating extracellular Ca2+ with EGTA. Genistein, an inhibitor of protein tyrosine kinases, significantly suppressed the Ang II-induced AA metabolite release. 1,6-Bis-(cyclohexyloximinocarbonylamino)-hexane (RHC-80267), a potent and selective inhibitor of diacylglycerol lipase, significantly inhibited the Ang II-induced AA metabolite release. Both propranolol and RHC-80267 inhibited the Ang II-induced synthesis of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin. The synthesis was suppressed by genistein. These results strongly suggest that the AA metabolite release induced by Ang II is mediated, at least in part, through phosphatidylcholine hydrolysis by phospholipase D activation in aortic smooth muscle cells.

  15. Acidity control of the oxidation reactions induced by non-thermal plasma treatment of aqueous effluents in pollutant abatement processes

    International Nuclear Information System (INIS)

    The acid properties of a non-thermal plasma in humid air (e.g., a gliding arc device) induced in an aqueous solution may deeply affect the efficiency of the matching oxidising properties, especially when the aqueous targets involve organic solutes. Hence, their oxidation rate may be strongly modified. A series of buffers is proposed to control the pH of aqueous target for at least one-hour treatments. The selected acid-base systems were selected for their inertia towards oxidation reaction, to cover a very large range of acidity. The reported results are essential from both fundamental and applied points of view. They first allow the acute controlling of the degradation rate of organic compounds. They also enable estimating the efficiency of the gliding arc treatments in environmental applications. Besides, they allow getting reliable data on the bactericidal effect on the plasma treatments, which are a merging application of the electric discharges. (author)

  16. Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides.

    Science.gov (United States)

    Park, J M; Higuchi, T; Kikuchi, K; Urano, Y; Hori, H; Nishino, T; Aoki, J; Inoue, K; Nagano, T

    2001-04-01

    The aim of this study was to investigate the structure-activity relationship of S-alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of these compounds on cytokine-induced NO production by human DLD-1 cells. In an in vitro assay, S-methyl-L-isothiocitrulline (L-MIT) was slightly selective for human neuronal NOS (nNOS) over the inducible (iNOS) or endothelial (eNOS) isozyme, but the combination of a hydrophobic L-amino acid (L-Phe, L-Leu or L-Trp) with L-MIT dramatically altered the inhibition pattern to give selective iNOS inhibitors. Introduction of a hydroxy, nitro, amino or methoxy group at the para position of the aromatic ring of L-MIT-L-Phe (MILF) decreased the selectivity and inhibitory potency. A longer or larger S-alkyl group also decreased the selectivity and potency. Dixon analysis showed that all of the dipeptides were competitive inhibitors of the three isoforms of human NOS. The enzymatic time course curves indicated that MILF was a slow binding inhibitor of human iNOS. These results suggest that the human NOS isozymes have different-sized cavities in the binding site near the position to which the C-terminal of L-arginine binds, and the cavity of iNOS is hydrophobic. Interestingly, L-MIT-D-Phe (MIDF) showed little inhibitory activity or selectivity, suggesting that the cavity of human iNOS is located in a well-defined direction from the alpha carbon atom. NO production in cytokine-stimulated human DLD-1 cells was measured with a fluorescent indicator, DAF-FM. MILF, L-MIT-L-Trp(-CHO) (MILW) and L-MIT-L-Tyr (MILY) showed more potent activity than L-MIT in this whole-cell assay. Thus, S-alkyl-L-isothiocitrulline-containing dipeptides are selective inhibitors of human iNOS, and work efficiently in cell-based assay. PMID:11309260

  17. Retinoic acid receptor gamma-induced misregulation of chondrogenesis in the murine limb bud in vitro.

    Science.gov (United States)

    Galdones, Eugene; Hales, Barbara F

    2008-11-01

    Vitamin A derivatives modulate gene expression through retinoic acid and rexinoid receptor (RAR/RXR) heterodimers and are indispensable for limb development. Of particular interest, RARgamma is highly expressed in cartilage, a target affected following retinoid-induced limb insult. The goal of this study was to examine how selective activation of RARgamma affects limb development. Forelimbs from E12.5 CD-1 mice were cultured for 6 days in the presence of all-trans RA (pan-RAR agonist; 0.1 or 1.0 microM) or BMS-189961 (BMS961, RARgamma-selective agonist; 0.01 or 0.1 microM) and limb morphology assessed. Untreated limbs developed normal cartilage elements whereas pan-RAR or RARgamma agonist-treated limbs exhibited reductive effects on chondrogenesis. Retinoid activity was assessed using RAREbeta2 (retinoic acid response element beta2)-lacZ reporter limbs; after 3 h of treatment, both drugs increased retinoid activity proximally. To elucidate the expression profiles of a subset of genes important for development, limbs were cultured for 3 h and cRNA hybridized to osteogenesis-focused microarrays. Two genes, matrix GLA protein (Mgp; chondrogenesis inhibitor) and growth differentiation factor-10 (Gdf10/Bmp3b) were induced by RA and BMS-189961. Real-time PCR was done to validate our results and whole mount in situ hybridizations against Mgp and Gdf10 localized their upregulation to areas of cartilage and programmed cell death, respectively. Thus, our results illustrate the importance of RARgamma in mediating the retinoid-induced upregulation of Mgp and Gdf10; determining their roles in chondrogenesis and cell death will help further unravel mechanisms underlying retinoid teratogenicity. PMID:18703560

  18. Cyclopiazonic acid alters serotonin-induced responses in rat thoracic aorta.

    Science.gov (United States)

    Selli, C; Erac, Y; Tosun, M

    2014-01-01

    We previously showed that endothelin A (ETA) receptor antagonist BQ-123 partially inhibited cyclopiazonic acid (CPA)-enhanced endothelin-1 (ET-1)-induced contractions suggesting enhancement of ETA receptor internalization in caveolar structures by sarco/endoplasmic reticulum Ca+2 ATPase (SERCA) blockade. Since serotonin (5-Hydroxytryptamine, 5-HT) receptors are reported to be localized on caveolar membranes, we investigated whether SERCA inhibition affects 5-HT-induced responses and 5-HT receptor antagonism. For this purpose, vascular responses were measured in thoracic aorta segments from male Wistar albino rats using isolated tissue experiments. Data showed that CPA inhibits 5-HT- and PE-induced contractions in intact vessels while potentiating those in endothelium-denuded. Furthermore, non-selective 5-HT receptor blocker methysergide partially inhibited CPA-induced 5-HT contractions. However, α1-adrenergic receptor antagonist prazosin totally inhibited CPA-potentiated PE contractions. We suggest that SERCA inhibition results in 5-HT receptor internalization similar to ETA receptors possibly through protein kinase C activation by increased subsarcolemmal Ca2+ levels, eventually preventing 5-HT receptor antagonism. PMID:24704610

  19. Calix[4]arene based selective fluorescent chemosensor for organic acid recognition

    Institute of Scientific and Technical Information of China (English)

    Runhe WANG; Jianhua BU; Junmin LIU; Shijun LIAO

    2008-01-01

    A novel calix[4]arene,based fluorescent chemosensor bearing a 2,aminopyridine moiety and a naphthalenic fluorophore was synthesized The chemical structure of the product was elucidated by FT,IR, MS,FAB, NMR and elemental analyses. Then, the properties and identification mechanism of the synthesized chemosensor were investigated. The results show that the chemosensor exhibits selective fluorescent quenching in the presence of aromatic organic acid in acetonitrile solution, and that the binding ability of the chemosensor with organic acid is in the order of p,cyanic,benzyl acid>p,chloric,benzyl acid>p,methoxyl,benzyl acid>benzyl acid.

  20. Crude protein, fibre and phytic acid in vitro digestibility of selected legume and buckwheat samples

    OpenAIRE

    Vojtíšková, Petra; Kráčmar, Stanislav

    2013-01-01

    The aim of this study was to determine crude protein, fi bre and phytic acid in vitro digestibility of selected legumes and buckwheat products. All analyses except the phytic acid contents were performed in the line with the Commission Regulation (EC) No. 152/2009. A modifi ed version of Holt's Method was used for phytic acid (phytate) determination. None of all samples contained more than 11% of moisture. Soybeans are rich in crude protein; they contain nearly 40% of this compound. The conte...

  1. Peracetic Acid Depolymerization of Biorefinery Lignin for Production of Selective Monomeric Phenolic Compounds.

    Science.gov (United States)

    Ma, Ruoshui; Guo, Mond; Lin, Kuan-Ting; Hebert, Vincent R; Zhang, Jinwen; Wolcott, Michael P; Quintero, Melissa; Ramasamy, Karthikeyan K; Chen, Xiaowen; Zhang, Xiao

    2016-07-25

    Lignin is the largest source of renewable material with an aromatic skeleton. However, due to the recalcitrant and heterogeneous nature of the lignin polymer, it has been a challenge to effectively depolymerize lignin and produce high-value chemicals with high selectivity. In this study, a highly efficient lignin-to-monomeric phenolic compounds (MPC) conversion method based on peracetic acid (PAA) treatment was reported. PAA treatment of two biorefinery lignin samples, diluted acid pretreated corn stover lignin (DACSL) and steam exploded spruce lignin (SESPL), led to complete solubilization and production of selective hydroxylated monomeric phenolic compounds (MPC-H) and monomeric phenolic acid compounds (MPC-A) including 4-hydroxy-2-methoxyphenol, p-hydroxybenzoic acid, vanillic acid, syringic acid, and 3,4-dihydroxybenzoic acid. The maximized MPC yields obtained were 18 and 22 % based on the initial weight of the lignin in SESPL and DACSL, respectively. However, we found that the addition of niobium pentoxide catalyst to PAA treatment of lignin can significantly improve the MPC yields up to 47 %. The key reaction steps and main mechanisms involved in this new lignin-to-MPC valorization pathway were investigated and elucidated. PMID:27373451

  2. Peracetic Acid Depolymerization of Biorefinery Lignin for Production of Selective Monomeric Phenolic Compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Ruoshui [Voiland School of Chemical Engineering and Bioengineering, Bioproducts, Science & Engineering Laboratory, Washington State University, 2710 Crimson Way Richland WA 99354 USA; Guo, Mond [Voiland School of Chemical Engineering and Bioengineering, Bioproducts, Science & Engineering Laboratory, Washington State University, 2710 Crimson Way Richland WA 99354 USA; Lin, Kuan-ting [Voiland School of Chemical Engineering and Bioengineering, Bioproducts, Science & Engineering Laboratory, Washington State University, 2710 Crimson Way Richland WA 99354 USA; Hebert, Vincent R. [Food and Environmental Laboratory, Washington State, University-TriCities, 2710 Crimson Way Richland WA 99354 USA; Zhang, Jinwen [Wood Materials and Engineering Laboratory, Washington State University, Pullman WA 99164 USA; Wolcott, Michael P. [Wood Materials and Engineering Laboratory, Washington State University, Pullman WA 99164 USA; Quintero, Melissa [Voiland School of Chemical Engineering and Bioengineering, Bioproducts, Science & Engineering Laboratory, Washington State University, 2710 Crimson Way Richland WA 99354 USA; Ramasamy, Karthikeyan K. [Chemical and Biological Process Development Group, Pacific Northwest National Laboratory, Richland WA 99354 USA; Chen, Xiaowen [National Bioenergy Center, National Renewable Energy Lab, 1617 Cole Blvd Golden CO 80127 USA; Zhang, Xiao [Voiland School of Chemical Engineering and Bioengineering, Bioproducts, Science & Engineering Laboratory, Washington State University, 2710 Crimson Way Richland WA 99354 USA

    2016-07-04

    Lignin is the largest source of renewable material with an aromatic skeleton. However, due to the recalcitrant and heterogeneous nature of the lignin polymer, it has been a challenge to effectively depolymerize lignin and produce high-value chemicals with high selectivity. In this study, a highly efficient lignin-to-monomeric phenolic compounds (MPC) conversion method based on peracetic acid (PAA) treatment was reported. PAA treatment of two biorefinery lignin samples, diluted acid pretreated corn stover lignin (DACSL) and steam exploded spruce lignin (SESPL), led to complete solubilization and production of selective hydroxylated monomeric phenolic compounds (MPC-H) and monomeric phenolic acid compounds (MPC-A) including 4-hydroxy-2-methoxyphenol, p-hydroxybenzoic acid, vanillic acid, syringic acid, and 3,4-dihydroxybenzoic acid. The maximized MPC yields obtained were 18 and 22 % based on the initial weight of the lignin in SESPL and DACSL, respectively. However, we found that the addition of niobium pentoxide catalyst to PAA treatment of lignin can significantly improve the MPC yields up to 47 %. The key reaction steps and main mechanisms involved in this new lignin-to-MPC valorization pathway were investigated and elucidated.

  3. Peracetic Acid Depolymerization of Biorefinery Lignin for Production of Selective Monomeric Phenolic Compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Ruoshui; Guo, Mond F.; Lin, Kuan-ting; Hebert, Vincent; Zhang, Jinwen; Wolcott, Michael P.; Quintero, Melissa; Ramasamy, Karthikeyan K.; Chen, Xiaowen; Zhang, Xiao

    2016-07-04

    Lignin is the largest source of renewable material with an aromatic skeleton. However, due to the recalcitrant and heterogeneous nature of the lignin polymer as well as its complex side chain structures, it has been a challenge to effectively depolymerize lignin and produce high value chemicals with high selectivity. In this study, a highly efficient lignin-to-monomeric phenolic compounds (MPC) conversion method based on peracetic acid (PAA) treatment was reported. PAA treatment of two biorefinery lignin samples, diluted acid pretreated corn stover lignin (DACSL) and steam exploded spruce lignin (SESPL), led to complete solubilization and production of selective hydroxylated monomeric phenolic compounds (MPC-H) and monomeric phenolic acid compounds (MPC-A) inclduing 4-hydroxy-2-methoxyphenol, p-hydroxybenzoic acid, vanillic acid, syringic acid, and 3,4-dihydroxybenzoic acid. The maximized MPCs yields obtained were 18% and 22% based on the initial weight of the lignin in SESPL and DACSL respectively. However, we found that the addition of niobium pentoxide catalyst to PAA treatment of lignin can significantly improve the MPC yields up to 47%. The key reaction steps and main mechanisms involved in this new lignin-to-MPC valorization pathway were investigated and elucidated.

  4. Stability of sublethal acid stress adaptaion and induced cross protection against lauric arginate in Listeria monocytogenes

    Science.gov (United States)

    The stability of acid stress adaptation in Listeria monocytogenes and its induced cross protection effect against GRAS (generally recognized as safe) antimicrobial compounds has never been investigated before. In the present study, the acid stress adaptation in L. monocytogenes was initially induced...

  5. Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction in Adolescents: A Review.

    Science.gov (United States)

    Scharko, Alexander M.

    2004-01-01

    Objective: To review the existing literature on selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction in adolescents. Method: A literature review of SSRI-induced adverse effects in adolescents focusing on sexual dysfunction was done. Nonsexual SSRI-induced adverse effects were compared in adult and pediatric populations.…

  6. Soybean Aphid Infestation Induces Changes in Fatty Acid Metabolism in Soybean.

    Directory of Open Access Journals (Sweden)

    Charles Kanobe

    Full Text Available The soybean aphid (Aphis glycines Matsumura is one of the most important insect pests of soybeans in the North-central region of the US. It has been hypothesized that aphids avoid effective defenses by inhibition of jasmonate-regulated plant responses. Given the role fatty acids play in jasmonate-induced plant defenses, we analyzed the fatty acid profile of soybean leaves and seeds from aphid-infested plants. Aphid infestation reduced levels of polyunsaturated fatty acids in leaves with a concomitant increase in palmitic acid. In seeds, a reduction in polyunsaturated fatty acids was associated with an increase in stearic acid and oleic acid. Soybean plants challenged with the brown stem rot fungus or with soybean cyst nematodes did not present changes in fatty acid levels in leaves or seeds, indicating that the changes induced by aphids are not a general response to pests. One of the polyunsaturated fatty acids, linolenic acid, is the precursor of jasmonate; thus, these changes in fatty acid metabolism may be examples of "metabolic hijacking" by the aphid to avoid the induction of effective defenses. Based on the changes in fatty acid levels observed in seeds and leaves, we hypothesize that aphids potentially induce interference in the fatty acid desaturation pathway, likely reducing FAD2 and FAD6 activity that leads to a reduction in polyunsaturated fatty acids. Our data support the idea that aphids block jasmonate-dependent defenses by reduction of the hormone precursor.

  7. [Epigenetic variability induced by nicotinic acid in Triticum aestivum L].

    Science.gov (United States)

    Bogdanova, E D

    2003-09-01

    The effect of nicotinic acid (NA) on hereditary traits of spring common wheat cultivar Kazakhstanskaya 126 (K.126) were studied under the laboratory and field conditions. Treatment of seeds and vegetating plants with 0.01-0.1% NA (aqueous solution) induced heritable epigenetic changes in wheat. As a result, strong tall plants with the long productive spike, large seeds, and several quantitative and qualitative characters other than in the original cultivar were obtained in the second and further generations after treatment. Crosses of changed plants with each other did not result in segregation with respect to leaf downiness or anthocyan stem color in F2-F4, suggesting the same epigenetic state of genes responsible for changed characters. In crosses with the original cultivar, characters of the changed plants always dominated in F1. Basing on the current views, the changes were attributed to a transition of the hl1 and pc recessive marker genes into new, dominant epiallelic states Hl1 and Pc, which respectively determine downy leaves and the colored stem. The NA effect was specific, since only one type of the variation was observed. The changed characters were stable, and no reversion to the original phenotype was detected in 57 generations. PMID:14582391

  8. Zoledronic acid induces apoptosis and autophagy in cervical cancer cells.

    Science.gov (United States)

    Wang, I-Te; Chou, Shou-Chu; Lin, Ying-Chin

    2014-12-01

    Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA-induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL-6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation.

  9. Fatty acid esters of phloridzin induce apoptosis of human liver cancer cells through altered gene expression.

    Directory of Open Access Journals (Sweden)

    Sandhya V G Nair

    Full Text Available Phloridzin (phlorizin or phloretin 2'-O-glucoside is known for blocking intestinal glucose absorption. We have investigated the anticarcinogenic effect of phloridzin and its novel derivatives using human cancer cell lines. We have synthesised novel acylated derivatives of phloridzin with six different long chain fatty acids by regioselective enzymatic acylation using Candida Antarctica lipase B. The antiproliferative effects of the new compounds were investigated in comparison with the parent compounds, phloridzin, aglycone phloretin, the six free fatty acids and chemotherapeutic drugs (sorafenib, doxorubicin and daunorubicin using human hepatocellular carcinoma HepG2 cells, human breast adenocarcinoma MDA-MB-231 cells and acute monocytic leukemia THP-1 cells along with normal human and rat hepatocytes. The fatty acid esters of phloridzin inhibited significantly the growth of the two carcinoma and leukemia cells while similar treatment doses were not toxic to normal human or rat hepatocytes. The antiproliferative potency of fatty esters of phloridzin was comparable to the potency of the chemotherapeutic drugs. The fatty acid esters of phloridzin inhibited DNA topoisomerases IIα activity that might induce G0/G1 phase arrest, induced apoptosis via activation of caspase-3, and decreased ATP level and mitochondrial membrane potential in HepG2 cells. Based on the high selectivity on cancer cells, decosahexaenoic acid (DHA ester of phloridzin was selected for gene expression analysis using RT2PCR human cancer drug target array. Antiproliferative effect of DHA ester of phloridzin could be related to the down regulation of anti-apoptotic gene (BCL2, growth factor receptors (EBFR family, IGF1R/IGF2, PDGFR and its downstream signalling partners (PI3k/AKT/mTOR, Ras/Raf/MAPK, cell cycle machinery (CDKs, TERT, TOP2A, TOP2B as well as epigenetics regulators (HDACs. These results suggest that fatty esters of phloridzin have potential chemotherapeutic effects

  10. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  11. The influence of stress conditions on the growth of selected lactic acid bacteria

    International Nuclear Information System (INIS)

    A study was undertaken to determine the effects of certain stress conditions on selected lactic acid bacteria. Where recontamination occurred, lactic acid bacteria was already the dominant bacterial group, with counts of higher than 106/g in vacuum-packaged 'shelf stable' meat products after 1 week storage at 25 and 37 degrees Celsius respectively. Some of the isolates were capable of growing at a pH of 3,9. The minimum pH for growth of a specific culture was dependant on the type of acid that was used to lower the pH. Lactic and acetic acid had the highest inhibitory action. Hydrochloric and citric acid showed similar inhibitory effects, while the effects when using ascorbic acid or gluconic acid for lowering the pH were also fairly similar. Increase in the activity of certain lactic acid bacteria was noticed where the ratio of undissociated to dissociated citric acid in the medium was increased. After exceeding a concentration of 0,048 moles/l undissosiated citric acid in the medium, the activity of the majority of cultures was progressively inhibited. This phenomenon was also found with acetic acid for certain cultures. Selected lactic acid bacteria were resistant to an water activity (a (sub w)) of 0,94 in MRS broth, where NaCl or glycerol was used as a humectant. The minimum a (sub w) for growth was dependent on the type of humectant used. Concentrations of sodium benzoate and potassium sorbate were necessary to inhibit the majority of strains. The % inhibition by sodium benzoate and methyl paraben did not significantly change with a lowering in the pH of the growth medium. Except in the case of lactic acid, the different acids used to lower the pH of the medium did not have a significant effect on the % inhibition by the chemical preservatives. For the cocci, gamma D10 values of between 0,82 and 1,29 kGy were recorded, whereas the lactobacilli were less resistant to gamma rays, with D10 values of between 0,21 and 0,54 kGy

  12. Deoxygenation of benzoic acid on metal oxides. I. The selective pathway to benzaldehyde

    NARCIS (Netherlands)

    Lange, de M.W.; Ommen, van J.G.; Lefferts, L.

    2001-01-01

    The mechanism of the selective deoxygenation of benzoic acid to benzaldehyde was studied on ZnO and ZrO2. The results show conclusively that the reaction proceeds as a reverse type of Mars and van Krevelen mechanism consisting of two steps: hydrogen activates the oxide by reduction resulting in the

  13. Selective oxidation of propane to acrylic acid over mixed metal oxide catalysts

    Institute of Scientific and Technical Information of China (English)

    Wei Zheng; Zhenxing Yu; Ping Zhang; Yuhang Zhang; Hongying Fu; Xiaoli Zhang; Qiquan Sun; Xinguo Hu

    2008-01-01

    The effects of metal atomic ratio, water content, oxygen content, and calcination temperature on the catalytic perfor-mances of MoVTeNbO mixed oxide catalyst system for the selective oxidation of propane to acrylic acid have been investigated and discussed. Among the catalysts studied, it was found that the MoVTeNbO catalyst calcined at a temperature of 600 ℃ showed the best performance in terms of propane conversion and selectivity for acrylic acid under an atmosphere of nitrogen. An effective MoVTeNbO oxide catalyst for propane selective oxidation to acrylic acid was obtained with a combination of a preferred metal atomic ratio (Mo1 V0.31Te0.23Nb0.12). The optimum reaction condition for the selective oxidation of propane was the molar ratio of C3H81 :O2 : H2O : N1 = 4.4 : 12.8 : 15.3 : 36.9. Under such conditions, the conversion of propane and the maximum yield of acrylic acid reached about 50% and 21%, respectively.

  14. Highly Selective Liquid-Phase Benzylation of Anisole with Solid-Acid Zeolite Catalysts

    DEFF Research Database (Denmark)

    Poreddy, Raju; Shunmugavel, Saravanamurugan; Riisager, Anders

    2015-01-01

    Zeolites were evaluated as solid acid catalysts for the liquid-phase benzylation of anisole with benzyl alcohol, benzyl bromide, and benzyl chloride at 80 °C. Among the examined zeolites, H-mordenite-10 (H-MOR-10) demonstrated particular high activity (>99 %) and excellent selectivity (>96...

  15. Molecularly imprinted titania nanoparticles for selective recognition and assay of uric acid

    Science.gov (United States)

    Mujahid, Adnan; Khan, Aimen Idrees; Afzal, Adeel; Hussain, Tajamal; Raza, Muhammad Hamid; Shah, Asma Tufail; uz Zaman, Waheed

    2015-06-01

    Molecularly imprinted titania nanoparticles are su ccessfully synthesized by sol-gel method for the selective recognition of uric acid. Atomic force microscopy is used to study the morphology of uric acid imprinted titania nanoparticles with diameter in the range of 100-150 nm. Scanning electron microscopy images of thick titania layer indicate the formation of fine network of titania nanoparticles with uniform distribution. Molecular imprinting of uric acid as well as its subsequent washing is confirmed by Fourier transformation infrared spectroscopy measurements. Uric acid rebinding studies reveal the recognition capability of imprinted particles in the range of 0.01-0.095 mmol, which is applicable in monitoring normal to elevated levels of uric acid in human blood. The optical shift (signal) of imprinted particles is six times higher in comparison with non-imprinted particles for the same concentration of uric acid. Imprinted titania particles have shown substantially reduced binding affinity toward interfering and structurally related substances, e.g. ascorbic acid and guanine. These results suggest the possible application of titania nanoparticles in uric acid recognition and quantification in blood serum.

  16. Defense signaling among interconnected ramets of a rhizomatous clonal plant, induced by jasmonic-acid application

    Science.gov (United States)

    Chen, Jin-Song; Lei, Ning-Fei; Liu, Qing

    2011-07-01

    Resource sharing between ramets of clonal plants is a well-known phenomenon that allows stoloniferous and rhizomatous species to internally transport water, mineral nutrients and carbohydrates from sites of high supply to sites of high demand. Moreover, vascular ramet connections are likely to provide an excellent means to share substances other than resources, such as defense signals. In a greenhouse experiment, the rhizomatous sedge Carex alrofusca, consisting of integrated ramets of different ages, was used to study the transmission of defense signals through belowground rhizome connections in response to local spray with jasmonic-acid. A feeding preference test with the caterpillar Gynaephora rnenyuanensis was employed to assess benefits of rhizome connections on defense signaling. Young ramets were more responsive to jasmonic-acid treatment than middle-aged or old ramets. Condensed tannin content in the foliage of young ramets showed a significant increase and soluble carbohydrate and nitrogen content showed marginally significant decreases in the 1 mM jasmonic-acid treatment but not in control and/or 0.0001 mM jasmonic-acid treatments. The caterpillar G. rnenyuanensis preferentially grazed young ramets. After a localized spray of 1 mM jasmonic-acid, the leaf area of young ramets consumed by herbivores was greatly reduced. We propose that defense signals may be transmitted through physical connections (stolon or rhizome) among interconnected ramets of clonal plants. Induced resistance to herbivory may selectively enhance the protection of more vulnerable and valuable plant tissues and confer a significant benefit to clonal plants by a modular risk-spreading strategy, equalizing ontogenetic differences of unevenly-aged ramets in chemical defense compounds and nutritional properties of tissue.

  17. Selective liquid phase oxidation of glycerol to glyceric acid over novel supported Pt catalysts

    Directory of Open Access Journals (Sweden)

    Sproge Elina

    2013-01-01

    Full Text Available Several supported platinum catalysts were prepared by extractive-pyrolytic method for the selective glyceric acid production from glycerol. Al2O3, Y2O3, Lu2O3, ZrO2-Y2O3 TiO2, SG, Fe2O3, γ-AlO(OH and C were used as catalyst supports, glycerol oxidation was carried out in the alkaline solutions and oxygen was used as oxidant. The optimal catalyst preparation parameters and glycerol oxidation conditions to obtain glyceric acid were determined. The best result (selectivity to glyceric acid 57% with glycerol conversion 92% was achieved in the presence of 4.8%Pt/Al2O3 catalyst.

  18. Cationic mononuclear ruthenium carboxylates as catalyst prototypes for self-induced hydrogenation of carboxylic acids

    Science.gov (United States)

    Naruto, Masayuki; Saito, Susumu

    2015-01-01

    Carboxylic acids are ubiquitous in bio-renewable and petrochemical sources of carbon. Hydrogenation of carboxylic acids to yield alcohols produces water as the only byproduct, and thus represents a possible next generation, sustainable method for the production of these alternative energy carriers/platform chemicals on a large scale. Reported herein are molecular insights into cationic mononuclear ruthenium carboxylates ([Ru(OCOR)]+) as prototypical catalysts for the hydrogenation of carboxylic acids. The substrate-derived coordinated carboxylate was found to function initially as a proton acceptor for the heterolytic cleavage of dihydrogen, and subsequently also as an acceptor for the hydride from [Ru–H]+, which was generated in the first step (self-induced catalysis). The hydrogenation proceeded selectively and at high levels of functional group tolerance, a feature that is challenging to achieve with existing heterogeneous/homogeneous catalyst systems. These fundamental insights are expected to significantly benefit the future development of metal carboxylate-catalysed hydrogenation processes of bio-renewable resources. PMID:26314266

  19. Inducible gene expression and environmentally regulated genes in lactic acid bacteria.

    Science.gov (United States)

    Kok, J

    1996-10-01

    Relatively recently, a number of genes and operons have been identified in lactic acid bacteria that are inducible and respond to environmental factors. Some of these genes/operons had been isolated and analysed because of their importance in the fermentation industry and, consequently, their transcription was studied and found to be regulatable. Examples are the lactose operon, the operon for nisin production, and genes in the proteolytic pathway of Lactococcus lactis, as well as xylose metabolism in Lactobacillus pentosus. Some other operons were specifically targetted with the aim to compare their mode of regulation with known regulatory mechanisms in other well-studied bacteria. These studies, dealing with the biosynthesis of histidine, tryptophan, and of the branched chain amino acids in L. lactis, have given new insights in gene regulation and in the occurrence of auxotrophy in these bacteria. Also, nucleotide sequence analyses of a number of lactococcal bacteriophages was recently initiated to, among other things, specifically learn more about regulation of the phage life cycle. Yet another approach in the analysis of regulated genes is the 'random' selection of genetic elements that respond to environmental stimuli and the first of such sequences from lactic acid bacteria have been identified and characterized. The potential of these regulatory elements in fundamental research and practical (industrial) applications will be discussed.

  20. Baicalein selectively induces apoptosis in activated lymphocytes and ameliorates concanavalin a-induced hepatitis in mice.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available BACKGROUND: Insufficient apoptosis in activated lymphocytes contributes to the development of autoimmune hepatitis (AIH. Baicalein (BE, a flavonoid originally isolated from the root of Scutellaria baicalensis Georgi, possesses anti-inflammatory properties. However, whether BE can selectively induce apoptosis in activated lymphocytes and exert therapeutic effect on AIH has not been studied. METHODOLOGY/PRINCIPAL FINDINGS: The pro-apoptotic properties of BE were evaluated in vitro on different types of immune cells, and in vivo effects of BE were examined in a murine model of Concanavalin A (Con A-induced hepatitis. In vitro treatment with BE resulted in a higher increase in the level of apoptosis in Con A-stimulated murine splenocytes, Con A-stimulated CD3(+ splenocytes, lipopolysaccharide (LPS-stimulated CD19(+ splenocytes, and phorbol 12-myristate 13-acetate/ionomycin-stimulated Jurkat T cells, compared with that in unstimulated naïve ones. Murine bone marrow-derived dentritic cells, peritoneal macrophages, and RAW264.7 cells, either stimulated with LPS or unstimulated, were all insensitive to the BE-induced apoptosis. BE treatment also led to a loss of mitochondrial membrane potential, an increase of cytochrome c release from mitochondria to the cytosol, a decrease in the ratio of Bcl-2/Bax, and activation of caspase-9,-3 in Con A-stimulated CD3(+ splenocytes and LPS-stimulated CD19(+ splenocytes, while showing no impact on Fas/FasL expressions and caspase-8 activation. In vivo administration of BE alleviated Con A-induced liver injury, suppressed serum level of TNF-α and IFN-γ, and reduced liver infiltration of mononuclear cells (MNCs. Furthermore, BE treatment increased the incidences of apoptosis in liver-infiltrating MNCs and splenocytes, as well as in CD3(+ and CD19(+ splenocytes. When liver MNCs and splenocytes from BE-treated mice were cultured in vitro for 24 h, they exhibited marked increase in apoptosis compared to vehicle

  1. A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Sløk, F A; Skjaerbaek, N;

    1996-01-01

    -methylisoxazol-4-yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino acid receptors (mGlu1 alpha, mGlu2, mGlu4a, and mGlu6). Whereas AMAA (6) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinoic acid (AMPA, 7) are potent and highly selective agonists at N...

  2. Soybean germplasms evaluation for acid tidal swamp tolerance using selection index

    Directory of Open Access Journals (Sweden)

    I Made Jana Mejaya

    2010-07-01

    Full Text Available Availability of fertile land on the island of Java in Indonesia decreases due to the shifting from agricultural land to non-agricultural land. Hence, an extensification of soybean culture to outer Java suboptimal land areas is needed, such as tidal swamp which occupies approximately 20.192 million hectares. The main limitations in this soil are soil acidity, Fe toxicity and excess water. To develop soybean varieties tolerant to acid tidal swamp, tolerant soybean gene resources are needed. Hence, glasshouse and field experiments were carried out to identify tolerant gene resources. The glasshouse experiment has been conducted using 185 genotypes of germplasm at the Indonesian Legume and Tuber Crops Research Institute, Malang, East Java. Selection was carried out by using a selection index method. The glasshouse experiment was followed by field experiment at the Belandean research station, Banjarbaru, South Kalimantan, using the best 17 genotypes selected from the glass­house trial. Results showed that there was variability of response of each genotype to acidity and Fe toxicity. Therefore, assessment of soybean tolerance to acidity and Fe toxicity should be conducted by root growth. Based on selection index criteria, varieties of Lawit and Menyapa served as check tolerant varieties and showed lower growth than the 17 selected genotypes. In the field experiment, genotype MLGG 1087 was identified as the most tolerant and can serve as a gene resource tolerant to acid tidal swamp because it has the highest relative root growth on root dry weight, and the highest average of root and shoot dry weight.

  3. PROBIOTIC PROPERTIES OF VAGINAL LACTIC ACID BACTERIA SELECTED FOR HARMONIZATION OF MICROENVIRONMENT OF REPRODUCTIVE APPARATUS

    Directory of Open Access Journals (Sweden)

    Eva Styková

    2012-08-01

    Full Text Available The aim of this study was isolation and screening of probiotic properties of Lactobacillus strains isolated from the vagina of heifers and cows with healthy reproductive apparatus. Initially tested properties were low pH tolerance, growth at different temperature, autoaggregation, fast growth and acid production. Strains were further tested for adherence to vaginal mucus. Negative selection was used and strains that did not meet tested criterion were excluded. From 244 samples taken from 122 heifers and cows were selected six strains of different taxa. Selected and identified were strains L. buchneri 5/K, L. buchneri 24S8, L. mucosae 29S8, L. mucosae 9/K and L. mucosae BiocenolTM 7697. These strains showed different biochemical properties also within a taxon and exhibited differences in the quantification of selection criteria. Further evaluation of the selected strain properties will be performed to consider their inclusion in a probiotic for local use in reproductive apparatus.

  4. Bayes Empirical Bayes Inference of Amino Acid Sites Under Positive Selection

    DEFF Research Database (Denmark)

    Yang, Ziheng; Wong, Wendy Shuk Wan; Nielsen, Rasmus

    2005-01-01

    Codon-based substitution models have been widely used to identify amino acid sites under positive selection in comparative analysis of protein-coding DNA sequences. The nonsynonymous-synonymous substitution rate ratio (dN/dS, denoted ) is used as a measure of selective pressure at the protein level......, with > 1 indicating positive selection. Statistical distributions are used to model the variation in among sites, allowing a subset of sites to have > 1 while the rest of the sequence may be under purifying selection with ... data sets. The results suggest that in small data sets the new BEB method does not generate false positives as did the old NEB approach, while in large data sets it retains the good power of the NEB approach for inferring positively selected sites....

  5. Stress -induced biosynthesis of dicaffeoylquinic acids in globe artichoke

    NARCIS (Netherlands)

    Moglia, A.; Lanteri, S.; Comino, C.; Acquadro, A.; Vos, de C.H.; Beekwilder, M.J.

    2008-01-01

    Leaf extracts from globe artichoke (Cynara cardunculus L. var. scolymus) have been widely used in medicine as hepatoprotectant and choleretic agents. Globe artichoke leaves represent a natural source of phenolic acids with dicaffeoylquinic acids, such as cynarin (1,3-dicaffeoylquinic acid), along wi

  6. Chiral selectivity of amino acid adsorption on chiral surfaces—The case of alanine on Pt

    Energy Technology Data Exchange (ETDEWEB)

    Franke, J.-H.; Kosov, D. S. [Department of Physics, Campus Plaine - CP 231, Université Libre de Bruxelles, 1050 Brussels (Belgium)

    2015-02-07

    We study the binding pattern of the amino acid alanine on the naturally chiral Pt surfaces Pt(531), Pt(321), and Pt(643). These surfaces are all vicinal to the (111) direction but have different local environments of their kink sites and are thus a model for realistic roughened Pt surfaces. Alanine has only a single methyl group attached to its chiral center, which makes the number of possible binding conformations computationally tractable. Additionally, only the amine and carboxyl group are expected to interact strongly with the Pt substrate. On Pt(531), we study the molecule in its pristine as well as its deprotonated form and find that the deprotonated one is more stable by 0.47 eV. Therefore, we study the molecule in its deprotonated form on Pt(321) and Pt(643). As expected, the oxygen and nitrogen atoms of the deprotonated molecule provide a local binding “tripod” and the most stable adsorption configurations optimize the interaction of this “tripod” with undercoordinated surface atoms. However, the interaction of the methyl group plays an important role: it induces significant chiral selectivity of about 60 meV on all surfaces. Hereby, the L-enantiomer adsorbs preferentially to the Pt(321){sup S} and Pt(643){sup S} surfaces, while the D-enantiomer is more stable on Pt(531){sup S}. The binding energies increase with increasing surface density of kink sites, i.e., they are largest for Pt(531){sup S} and smallest for Pt(643){sup S}.

  7. Trifluoroacetic acid as excipient destabilizes melittin causing the selective aggregation of melittin within the centrin-melittin-trifluoroacetic acid complex.

    Science.gov (United States)

    Pastrana-Rios, Belinda; Del Valle Sosa, Liliana; Santiago, Jorge

    2015-07-01

    Trifluoroacetic acid (TFA) may be the cause of the bottleneck in high resolution structure determination for protein-peptide complexes. Fragment based drug design often involves the use of synthetic peptides which contain TFA (excipient). Our goal was to explore the effects of this excipient on a model complex: centrin-melittin-TFA. We performed Fourier transform infrared, two-dimensional infrared correlation spectroscopies and spectral simulations to analyze the amide I'/I'* band for the components and the ternary complex. Melittin (MLT) was observed to have increased helicity upon its interaction with centrin, followed by the thermally induced aggregation of MLT within the ternary complex in the TFA presence. PMID:26798810

  8. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    Science.gov (United States)

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  9. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

    Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

  10. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors

    OpenAIRE

    Tunaru, Sorin; Althoff, Till F.; Nüsing, Rolf M.; Diener, Martin; Offermanns, Stefan

    2012-01-01

    Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP3 prostanoid receptor is specifically activated by ricinoleic acid and...

  11. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    Directory of Open Access Journals (Sweden)

    Nur Shafika Mohd Sairazi

    2015-01-01

    Full Text Available Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS. In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA. KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  12. Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats.

    Science.gov (United States)

    Pedraza, Carmen; García, Francisca Belén; Navarro, José Francisco

    2009-10-01

    Gammahydroxybutyric acid (GHB) is an endogenous constituent of the central nervous system that has acquired great social relevance for its use as a recreational 'club drug'. GHB, popularly known as 'liquid ecstasy', is addictive when used continuously. Although the symptoms associated with acute intoxication are well known, the effects of prolonged use remain uncertain. We examined in male rats the effect of repeated administration of GHB (10 and 100 mg/kg) on various parameters: neurological damage, working memory and spatial memory, using neurological tests, the Morris water maze and the hole-board test. The results showed that repeated administration of GHB, especially at doses of 10 mg/kg, causes neurological damage, affecting the 'grasping' reflex, as well as alteration in spatial and working memories. Stereological quantification showed that this drug produces a drastic neuronal loss in the CA1 hippocampal region and in the prefrontal cortex, two areas clearly involved in cognitive and neurological functions. No effects were noted after quantification in the periaqueductal grey matter (PAG), a region lacking GHB receptors. Moreover, NCS-382, a putative antagonist of GHB receptor, prevented both neurological damage and working- memory impairment induced by GHB. This suggests that the effects of administration of this compound may be mediated, at least partly, by specific receptors in the nervous system. The results show for the first time that the repeated administration of GHB, especially at very low doses, produces neurotoxic effects. This is very relevant because its abuse, especially by young persons, could produce considerable neurological alterations after prolonged abuse.

  13. Trihydroxybenzoic Acid Dimer-induced Apoptosis Effects in vitro

    Institute of Scientific and Technical Information of China (English)

    NIU Feng-lan; WANG Xue-dong; WANG Ying-li; SONG Lian-sheng

    2005-01-01

    The in vitro inhibitory effect of trihydroxybenzoic acid dimer(TAD) extracted from Trapabispinosd roxb on HeLa cell growth was investigated via the MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diophenyl-tetrazolium bromide] reduction method. The morphological changes of HeLa cells were observed by means of an optical microscope and a transmission electron microscope(TEM); the cell circles and apoptosis were detected by a flow cytometer. It was found that TAD can significantly inhibit the growth of Hela cells and can induce the apoptosis of HeLa cells. It was also found that the inhibition to the growth of Hela cells and the induction to the apoptosis of HeLa cells have a dosage-dependent feature. The inhibiting rates of TAD with mass concentrations of 25.000, 12.500 and 6.250 mg/L to the HeLa cell growth were 52.04%, 34.44% and 23.72% after 30 h, respectively, while those with TAD mass concentrations of 100.000, 50.000, 25.000, 12.500, 6.250 and 3.125 mg/L showed positive correlation with a correlation coefficient value of r=0.9859(P<0.01) and a IC50 value of 10.90 mg/L. Observed by means of TEM, the HeLa cells exposed to 25.000, 12.500 and 6.250 mg/L TAD showed apoptosis to various extents, shrinkage of the cell nuclei, condensation and margination of chromatin, and cavitation of mitochondrion. An apoptosis peak was detected via a flow cytometer. It can be drawn from the results that TAD extracted from Trapabispinosd roxb has an evident inhibitory effect on the proliferation of and an inductive effect on the apoptosis of HeLa cells, but has no obvious arrest action towards the cell circles of HeLa cells.

  14. CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

    Science.gov (United States)

    Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

    2012-01-01

    The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

  15. Chronic gamma radiation-induced changes in the content of fatty acids in spring rape seeds

    International Nuclear Information System (INIS)

    Chronic gamma irradiation of spring rape plants having no erucic acid and eicosanoic acid in seed oil induced changes both in the growth and in the morphological composition of the plants. The contents of erucic acid and eicosanoic acid did not increase. The greatest changes occurred in unsaturated acids, especially in macromutants resulting from irradiated plants located in the closest proximity of the radiation source or in places with the most significant plant growth inhibition. Nutants with a low, or a high, content of linolenic acid were obtained. (author)

  16. Potentiation of the teratogenic effects induced by coadministration of retinoic acid or phytanic acid/phytol with synthetic retinoid receptor ligands.

    Science.gov (United States)

    Elmazar, M M A; Nau, H

    2004-11-01

    Previous studies in our laboratory identified retinoid-induced defects that are mediated by RAR-RXR heterodimerization using interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997, Toxicol Appl Pharmacol 146:21-28; Elmazar et al. 2001, Toxicol Appl Pharmacol 170:2-9; Nau and Elmazar 1999, Handbook of experimental pharmacology, vol 139, Retinoids, Springer-Verlag, pp 465-487). The present study was designed to investigate whether these RAR-RXR heterodimer-mediated defects can be also induced by interactions of natural and synthetic ligands for retinoid receptors. A non-teratogenic dose of the natural RXR agonist phytanic acid (100 mg/kg orally) or its precursor phytol (500 mg/kg orally) was coadministered with a synthetic RARalpha-agonist (Am580; 5 mg/kg orally) to NMRI mice on day 8.25 of gestation (GD8.25). Furthermore, a non-teratogenic dose of the synthetic RXR agonist LGD1069 (20 mg/kg orally) was also coadministered with the natural RAR agonist, all- trans-retinoic acid (atRA, 20 mg/kg orally) or its precursor retinol (ROH, 50 mg/kg orally) to NMRI mice on GD8.25. The teratogenic outcome was scored in day-18 fetuses. The incidence of Am580-induced resorptions, spina bifida aperta, micrognathia, anotia, kidney hypoplasia, dilated bladder, undescended testis, atresia ani, short and absent tail, fused ribs and fetal weight retardation were potentiated by coadministration of phytanic acid or its precursor phytol. Am580-induced exencephaly and cleft palate, which were not potentiated by coadministration with the synthetic RXR agonists, were also not potentiated by coadministration with either phytanic acid or its precursor phytol. LGD1069 potentiated atRA- and ROH-induced resorption, exencephaly, spina bifida, aperta, ear anotia and microtia, macroglossia, kidney hypoplasia, undescended testis, atresia ani, tail defects and fetal weight retardation, but not cleft palate. These results suggest that synergistic

  17. Using In Vitro Immunomodulatory Properties of Lactic Acid Bacteria for Selection of Probiotics against Salmonella Infection in Broiler Chicks.

    Directory of Open Access Journals (Sweden)

    Junchang Feng

    Full Text Available Poultry is known to be a major reservoir of Salmonella. The use of lactic acid bacteria has become one of successful strategies to control Salmonella in poultry. The purpose of this study was to select lactic acid bacteria strains by their in vitro immunomodulatory properties for potential use as probiotics against Salmonella infection in broiler chicks. Among 101 isolated lactic acid bacteria strains, 13 strains effectively survived under acidic (pH 2.5 and bile salt (ranging from 0.1% to 1.0% conditions, effectively inhibited growth of 6 pathogens, and adhered to Caco-2 cells. However, their in vitro immunomodulatory activities differed significantly. Finally, three strains with higher in vitro immunomodulatory properties (Lactobacillus plantarum PZ01, Lactobacillus salivarius JM32 and Pediococcus acidilactici JH231 and three strains with lower in vitro immunomodulatory activities (Enterococcus faecium JS11, Lactobacillus salivarius JK22 and Lactobacillus salivarius JM2A1 were compared for their inhibitory effects on Salmonella adhesion and invasion to Caco-2 cells in vitro and their antimicrobial effects in vivo. The former three strains inhibited Salmonella adhesion and invasion to Caco-2 cells in vitro, reduced the number of Salmonella in intestinal content, spleen and liver, reduced the levels of lipopolysaccharide-induced TNF-α factor (LITAF, IL-1β, IL-6 and IL-12 in serum and increased the level of IL-10 in serum during a challenge study in vivo more efficiently than the latter three strains. These results suggest that in vitro immunomodulatory activities could be used as additional parameters to select more effective probiotics as feed supplements for poultry.

  18. Using In Vitro Immunomodulatory Properties of Lactic Acid Bacteria for Selection of Probiotics against Salmonella Infection in Broiler Chicks.

    Science.gov (United States)

    Feng, Junchang; Wang, Lihong; Zhou, Luoxiong; Yang, Xin; Zhao, Xin

    2016-01-01

    Poultry is known to be a major reservoir of Salmonella. The use of lactic acid bacteria has become one of successful strategies to control Salmonella in poultry. The purpose of this study was to select lactic acid bacteria strains by their in vitro immunomodulatory properties for potential use as probiotics against Salmonella infection in broiler chicks. Among 101 isolated lactic acid bacteria strains, 13 strains effectively survived under acidic (pH 2.5) and bile salt (ranging from 0.1% to 1.0%) conditions, effectively inhibited growth of 6 pathogens, and adhered to Caco-2 cells. However, their in vitro immunomodulatory activities differed significantly. Finally, three strains with higher in vitro immunomodulatory properties (Lactobacillus plantarum PZ01, Lactobacillus salivarius JM32 and Pediococcus acidilactici JH231) and three strains with lower in vitro immunomodulatory activities (Enterococcus faecium JS11, Lactobacillus salivarius JK22 and Lactobacillus salivarius JM2A1) were compared for their inhibitory effects on Salmonella adhesion and invasion to Caco-2 cells in vitro and their antimicrobial effects in vivo. The former three strains inhibited Salmonella adhesion and invasion to Caco-2 cells in vitro, reduced the number of Salmonella in intestinal content, spleen and liver, reduced the levels of lipopolysaccharide-induced TNF-α factor (LITAF), IL-1β, IL-6 and IL-12 in serum and increased the level of IL-10 in serum during a challenge study in vivo more efficiently than the latter three strains. These results suggest that in vitro immunomodulatory activities could be used as additional parameters to select more effective probiotics as feed supplements for poultry.

  19. 4-Mercaptophenylboronic acid functionalized graphene oxide composites: Preparation, characterization and selective enrichment of glycopeptides.

    Science.gov (United States)

    Jiang, Bo; Qu, Yanyan; Zhang, Lihua; Liang, Zhen; Zhang, Yukui

    2016-03-17

    Selective enrichment and isolation of glycopeptides from complex biological samples was indispensable for mass spectrometry (MS)-based glycoproteomics, however, it remained a great challenge due to the low abundance of glycoproteins and the ion suppression of non-glycopeptides. In this work, 4-mercaptophenylboronic acid functionalized graphene oxide composites were synthesized via loading gold nanoparticles on polyethylenimine modified graphene oxide surface, followed by 4-mercaptophenylboronic acid immobilization by the formation of Au-S bonding (denoted as GO/PEI/Au/4-MPB composites). The composites showed highly specific and efficient capture of glycopeptides due to their excellent hydrophilicity and abundant boronic acid groups. The composites could selectively capture the glycopeptides from the mixture of glycopeptides and nonglycopeptides, even when the amounts of non-glycopeptides were 100 times more than glycopeptides. Compared with commercial meta-amino phenylboronic acid agarose, the composites showed better selectivity when the sample was decreased to 10 ng. These results clearly verified that the GO/PEI/Au/4-MPB composites might be a promising material for glycoproteomics analysis.

  20. Antagonist Effects of Veratric Acid against UVB-Induced Cell Damages

    Directory of Open Access Journals (Sweden)

    Deokhoon Park

    2013-05-01

    Full Text Available Ultraviolet (UV radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs formation, glutathione (GSH depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection.

  1. Electroless Plating on Plastic Induced by Selective Laser Activation

    DEFF Research Database (Denmark)

    Zhang, Yang; Tang, Peter Torben; Hansen, Hans Nørgaard;

    2009-01-01

    This paper presents a new method for selective micro metallization of polymers. A Nd:YAG laser is employed to draw patterns on polymer surfaces that are submerged in a liquid (usually water). After subsequent activation with palladium chloride and followed by auto-catalytic electroless plating, c...

  2. Wet oxidation of glycerol into fine organic acids: catalyst selection and kinetic evaluation

    Directory of Open Access Journals (Sweden)

    J. E. N. Brainer

    2014-12-01

    Full Text Available The liquid phase oxidation of glycerol was performed producing fine organic acids. Catalysts based on Pt, Pd and Bi supported on activated carbon were employed to perform the conversion of glycerol into organic acids at 313 K, 323 K and 333 K, under atmospheric pressure (1.0 bar, in a mechanically agitated slurry reactor (MASR. The experimental results indicated glycerol conversions of 98% with production of glyceric, tartronic and glycolic acids, and dihydroxyacetone. A yield of glyceric acid of 69.8%, and a selectivity of this compound of 70.6% were reached after 4 h of operation. Surface mechanisms were proposed and rate equations were formulated to represent the kinetic behavior of the process. Selective formation of glyceric acid was observed, and the kinetic parameter values indicated the lowest activation energy (38.5 kJ/mol for its production reaction step, and the highest value of the adsorption equilibrium constant of the reactant glycerol (10-4 dm³/mol.

  3. MUSIC in triple-resonance experiments: amino acid type-selective (1)H-(15)N correlations

    Science.gov (United States)

    Schubert; Smalla; Schmieder; Oschkinat

    1999-11-01

    Amino acid type-selective triple-resonance experiments can be of great help for the assignment of protein spectra, since they help to remove ambiguities in either manual or automated assignment procedures. Here, modified triple-resonance experiments that yield amino acid type-selective (1)H-(15)N correlations are presented. They are based on novel coherence transfer schemes, the MUSIC pulse sequence elements, that replace the initial INEPT transfer and are selective for XH(2) or XH(3) (X can be (15)N or (13)C). The desired amino acid type is thereby selected based on the topology of the side chain. Experiments for Gly (G-HSQC); Ala (A-HSQC); Thr, Val, Ile, and Ala (TAVI-HSQC); Thr and Ala (TA-HSQC), as well as Asn and Gln (N-HSQC and QN-HSQC), are described. The new experiments are recorded as two-dimensional experiments and therefore need only small amounts of spectrometer time. The performance of the experiments is demonstrated with the application to two protein domains. Copyright 1999 Academic Press. PMID:10527741

  4. Novel long chain fatty acid derivatives of quercetin-3-O-glucoside reduce cytotoxicity induced by cigarette smoke toxicants in human fetal lung fibroblasts.

    Science.gov (United States)

    Warnakulasuriya, Sumudu N; Ziaullah; Rupasinghe, H P Vasantha

    2016-06-15

    Smoking has become a global health concern due to its association with many disease conditions, such as chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD) and cancer. Flavonoids are plant polyphenolic compounds, studied extensively for their antioxidant, anti-inflammatory, and anti-carcinogenic properties. Quercetin-3-O-glucoside (Q3G) is a flavonoid which is widely found in plants. Six novel long chain fatty acid [stearic acid, oleic acid, linoleic acid, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] derivatives of Q3G were evaluated for their potential in protecting human lung fibroblasts against cytotoxicity induced by selected cigarette smoke toxicants: 4-(methylnitrosoamino)-1-(3-pyridinyl)-1-butanone (NNK), benzo-α-pyrene (BaP), nicotine and chromium (Cr[VI]). Nicotine and Cr[VI] induced toxicity in fibroblasts and reduced the percentage of viable cells, while BaP and NNK did not affect cell viability. The fatty acid derivatives of Q3G provided protection against nicotine- and Cr[VI]-induced cell death and membrane lipid peroxidation. Based on the evaluation of inflammatory markers of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), the fatty acid derivatives of Q3G were found to be effective in lowering the inflammatory response. Overall, these novel fatty acid esters of Q3G warrant further investigation as potential cytoprotective agents. PMID:27071958

  5. Mass spectrometric analysis of selected radiolyzed amino acids in an astrochemical context

    International Nuclear Information System (INIS)

    A selection of amino acids, namely arginine, proline and tyrosine previously irradiated to 3.2 mega-Gray in the solid state and analyzed by differential scanning calorimetry (DSC) and optical rotatory dispersion (ORD) were analyzed in the present work by mass spectrometry with the purpose to identify the radiolysis products and validate the results obtained previously with DSC and ORD. The radiolysis of amino acids is a top-down approach of a research program designed to assess the radiolysis resistance of these molecules for 4.6 x 109 years once buried in primitive bodies of the Solar System. (author)

  6. Acetic Acid Formation by Selective Aerobic Oxidation of Aqueous Ethanol over Heterogeneous Ruthenium Catalysts

    DEFF Research Database (Denmark)

    Gorbanev, Yury; Kegnæs, Søren; Hanning, Christopher William;

    2012-01-01

    Heterogeneous catalyst systems comprising ruthenium hydroxide supported on different carrier materials, titania, alumina, ceria, and spinel (MgAl2O4), were applied in selective aerobic oxidation ethanol to form acetic acid, an important bulk chemical and food ingredient. The catalysts were...... of catalysts, oxidant pressure, reaction temperature, and substrate concentration were investigated. Quantitative yield of acetic acid was obtained with 1.2 wt % Ru(OH)x/CeO2 under optimized conditions (150 °C, 10 bar O2, 12 h of reaction time, 0.23 mol % Ru to substrate)....

  7. Technological innovation of induced breeding of space and selection of new variety on pepper

    International Nuclear Information System (INIS)

    New pepper variety Yujiao No.1 and new pepper lines with different horticultural characters are obtained by new breeding technique: combination of space inducement and regular breeding, field selection and inherited marker

  8. Microcultures of lactic acid bacteria: characterization and selection of strains, optimization of nutrients and gallic acid concentration.

    Science.gov (United States)

    Guzmán-López, Oswaldo; Loera, Octavio; Parada, José Luis; Castillo-Morales, Alberto; Martínez-Ramírez, Cándida; Augur, Christopher; Gaime-Perraud, Isabelle; Saucedo-Castañeda, Gerardo

    2009-01-01

    Eighteen lactic acid bacteria (LAB) strains, isolated from coffee pulp silages were characterized according to both growth and gallic acid (GA) consumption. Prussian blue method was adapted to 96-well microplates to quantify GA in LAB microcultures. Normalized data of growth and GA consumption were used to characterize strains into four phenotypes. A number of 5 LAB strains showed more than 60% of tolerance to GA at 2 g/l; whereas at 10 g/l GA growth inhibition was detected to a different extent depending on each strain, although GA consumption was observed in seven studied strains (>60%). Lactobacillus plantarum L-08 was selected for further studies based on its capacity to degrade GA at 10 g/l (97%). MRS broth and GA concentrations were varied to study the effect on growth of LAB. Cell density and growth rate were optimized by response surface methodology and kinetic analysis. Maximum growth was attained after 7.5 h of cultivation, with a dilution factor of 1-1/2 and a GA concentration between 0.625 and 2.5 g/l. Results indicated that the main factor affecting LAB growth was GA concentration. The main contribution of this study was to propose a novel adaptation of a methodology to characterize and select LAB strains with detoxifying potential of simple phenolics based on GA consumption and tolerance. In addition, the methodology presented in this study integrated the well-known RSM with an experimental design based on successive dilutions.

  9. Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Lei Yu; Yang-De Zhang; Jun Zhou; De-Ming Yao; Xiang Li

    2013-01-01

    Objective: To indentify target genes of transcription factor CCAAT enhancer-binding proteinβ (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid. Methods:A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified. Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA. Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.

  10. Dual role of endogenous serotonin in 2,4,6-trinitrobenzene sulfonic acid-induced colitis

    Directory of Open Access Journals (Sweden)

    Alberto eRapalli

    2016-03-01

    Full Text Available Background and Aims: Changes in gut serotonin content have been described in Inflammatory Bowel Disease and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous serotonin through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of Inflammatory Bowel Disease. Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135, 5-HT2A (Ketanserin, 5-HT3 (Ondansetron, 5-HT4 (GR125487, 5-HT7 (SB269970 receptors and with 5-HT1A agonist 8-Hydroxy-2-(di-n-propylaminotetralin. Results: Blockade of 5-HT1A receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5-HT1A agonist delayed and mitigated the severity of colitis, counteracting the increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors improved global health conditions, reduced colonic morphological alterations, down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic apoptosis. Antagonism of 5-HT3, 5-HT4 and 5-HT7 receptor sites did not remarkably affect the progression and outcome of the pathology or only slightly improved it.Conclusions: The prevailing deleterious contribution given by endogenous serotonin to inflammation in TNBS-induced colitis is seemingly mediated by 5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only a selective interference with 5-HT pro-inflammatory actions may represent an additional potential therapeutic option for intestinal inflammatory disorders.

  11. Electric Field Induced Selective Disordering in Lamellar Block Copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Ruppel, Markus A [ORNL; Pester, Christian W [ORNL; Langner, Karol M [Leiden Institute of Chemistry, Leiden University, The Netherlands; Sevink, Geert [Leiden Institute of Chemistry, Leiden University, The Netherlands; Schoberth, Heiko [University of Bayreuth; Schmidt, Kristin [ORNL; Urban, Volker S [ORNL; Mays, Jimmy [ORNL; Boker, Alexander [RWTH Aachen University

    2013-01-01

    External electric fields align nanostructured block copolymers by either rotation of grains or nucleation and growth depending on how strongly the chemically distinct block copolymer components are segregated. In close vicinity to the orderdisorder transition, theory and simulations suggest a third mechanism: selective disordering. We present a time-resolved small-angle X-ray scattering study that demonstrates how an electric field can indeed selectively disintegrate ill-aligned lamellae in a lyotropic block copolymer solution, while lamellae with interfaces oriented parallel to the applied field prevail. The present study adds an additional mechanism to the experimentally corroborated suite of mechanistic pathways, by which nanostructured block copolymers can align with an electric field. Our results further unveil the benefit of electric field assisted annealing for mitigating orientational disorder and topological defects in block copolymer mesophases, both in close vicinity to the orderdisorder transition and well below it.

  12. Interactions of zinc octacarboxyphthalocyanine with selected amino acids and with albumin

    Science.gov (United States)

    Kliber, Marta; Broda, Małgorzata A.; Nackiewicz, Joanna

    2016-02-01

    Effect of selected amino acids (glycine, L-histidine, L-cysteine, L-serine, L-tryptophan) and albumin on the spectroscopic properties and photostability of zinc octacarboxyphthalocyanine (ZnPcOC) was explored in the phosphate buffer at a pH of 7.0. The photodegradation of ZnPcOC alone and in the presence of amino acids or albumin has been investigated in aqueous phase using UV-366 nm and daylight irradiation. Kinetic analysis showed that the interaction with amino acids or albumin enhances the photostability of ZnPcOC. To answer the question of how zinc phthalocyanine interacts with amino acids extensive DFT calculations were performed. Analysis of the optimized geometry features of ZnPcOC: amino acids complexes in the gas phase and in water environment as well as the BSSE corrected interaction energies indicates that the more likely is the formation of equatorial complexes in which H-bonds are formed between the COOH groups of the phthalocyanine and carboxyl or amino groups of amino acids. UV-Vis spectra calculated by employing time dependent density functional theory (TD-DFT) are also consistent with this conclusion.

  13. Interactions of zinc octacarboxyphthalocyanine with selected amino acids and with albumin.

    Science.gov (United States)

    Kliber, Marta; Broda, Małgorzata A; Nackiewicz, Joanna

    2016-02-15

    Effect of selected amino acids (glycine, l-histidine, l-cysteine, l-serine, l-tryptophan) and albumin on the spectroscopic properties and photostability of zinc octacarboxyphthalocyanine (ZnPcOC) was explored in the phosphate buffer at a pH of 7.0. The photodegradation of ZnPcOC alone and in the presence of amino acids or albumin has been investigated in aqueous phase using UV-366nm and daylight irradiation. Kinetic analysis showed that the interaction with amino acids or albumin enhances the photostability of ZnPcOC. To answer the question of how zinc phthalocyanine interacts with amino acids extensive DFT calculations were performed. Analysis of the optimized geometry features of ZnPcOC: amino acids complexes in the gas phase and in water environment as well as the BSSE corrected interaction energies indicates that the more likely is the formation of equatorial complexes in which H-bonds are formed between the COOH groups of the phthalocyanine and carboxyl or amino groups of amino acids. UV-Vis spectra calculated by employing time dependent density functional theory (TD-DFT) are also consistent with this conclusion.

  14. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

    Science.gov (United States)

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-09

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-01

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

  16. Leishmania donovani Utilize Sialic Acids for Binding and Phagocytosis in the Macrophages through Selective Utilization of Siglecs and Impair the Innate Immune Arm

    Science.gov (United States)

    Roy, Saptarshi; Mandal, Chitra

    2016-01-01

    Background Leishmania donovani, belonging to a unicellular protozoan parasite, display the differential level of linkage-specific sialic acids on their surface. Sialic acids binding immunoglobulin-like lectins (siglecs) are a class of membrane-bound receptors present in the haematopoetic cell lineages interact with the linkage-specific sialic acids. Here we aimed to explore the utilization of sialic acids by Leishmania donovani for siglec-mediated binding, phagocytosis, modulation of innate immune response and signaling pathways for establishment of successful infection in the host. Methodology/Principle Findings We have found enhanced binding of high sialic acids containing virulent strains (AG83+Sias) with siglec-1 and siglec-5 present on macrophages compared to sialidase treated AG83+Sias (AG83-Sias) and low sialic acids-containing avirulent strain (UR6) by flow cytometry. This specific receptor-ligand interaction between sialic acids and siglecs were further confirmed by confocal microscopy. Sialic acids-siglec-1-mediated interaction of AG83+Sias with macrophages induced enhanced phagocytosis. Additionally, sialic acids-siglec-5 interaction demonstrated reduced ROS, NO generation and Th2 dominant cytokine response upon infection with AG83+Sias in contrast to AG83-Sias and UR6. Sialic acids-siglecs binding also facilitated multiplication of intracellular amastigotes. Moreover, AG83+Sias induced sialic acids-siglec-5-mediated upregulation of host phosphatase SHP-1. Such sialic acids-siglec interaction was responsible for further downregulation of MAPKs (p38, ERK and JNK) and PI3K/Akt pathways followed by the reduced translocation of p65 subunit of NF-κβ to the nucleus from cytosol in the downstream signaling pathways. This sequence of events was reversed in AG83-Sias and UR6-infected macrophages. Besides, siglec-knockdown macrophages also showed the reversal of AG83+Sias infection-induced effector functions and downstream signaling events. Conclusions

  17. Selective extraction of metals from products of mine acidic water treatment

    International Nuclear Information System (INIS)

    A study was made on possibility of processing of foam products prepared during flotation purification of mine acidic waters for the purpose of selective extraction of non-ferrous (Co, Ni) and rare earth elements (REE) and their separation from the basic macrocomponent of waters-iron. Optimal conditions of selective metal extraction from foam flotation products are the following: T=333 K, pH=3.0-3.5, ratio of solid and liquid phase - 1:4-1:7, duration of sulfuric acid leaching - 30 min. Rare earth extraction under such conditions equals 87.6-93.0%. The degree of valuable component concentration equals ∼ 10. Rare earths are separated from iron by extraction methods

  18. Synthesis of Homoveratric Acid-Imprinted Polymers and Their Evaluation as Selective Separation Materials

    Directory of Open Access Journals (Sweden)

    Mariusz Dana

    2011-05-01

    Full Text Available A bulk polymerization method was used to easily and efficiently prepare homo-veratric acid (3,4-dimethoxyphenylacetic acid-imprinted polymers from eight basic monomers: 2-vinylpyridine, 4-vinylpyridine, 1-vinylimidazole, N-allylaniline, N-allylpiperazine, allylurea, allylthiourea, and allylamine, in the presence of homoveratric acid as a template in N,N-dimethylformamide as a porogen. The imprinted polymer prepared from allylamine had the highest affinity to the template, showing an imprinting factor of 3.43, and allylamine polymers MIP8/NIP8 were selected for further studies. Their binding properties were analyzed using the Scatchard method. The results showed that the imprinted polymers have two classes of heterogeneous binding sites characterized by two pairs of Kd, Bmax values: Kd(1 = 0.060 μmol/mL, Bmax(1 = 0.093 μmol/mg for the higher affinity binding sites, and Kd(2 = 0.455 μmol/mL, Bmax(2 = 0.248 μmol/mg for the lower affinity binding sites. Non-imprinted polymer has only one class of binding site, with Kd = 0.417 μmol/mL and Bmax = 0.184 μmol/mg. A computational analysis of the energies of the prepolymerization complexes was in agreement with the experimental results. It showed that the selective binding interactions arose from cooperative three point interactions between the carboxylic acid and the two methoxy groups in the template and amino groups in the polymer cavities. Those results were confirmed by the recognition studies performed with the set of structurally related compounds. Allylamine polymer MIP8 had no affinity towards biogenic amines. The obtained imprinted polymer could be used for selective separation of homoveratric acid.

  19. A Multiwall Carbon Nanotube-chitosan Modified Electrode for Selective Detection of Dopamine in the Presence of Ascorbic Acid

    Institute of Scientific and Technical Information of China (English)

    Ling Yan JIANG; Chuan Yin LIU; Li Ping JIANG; Guang Han LU

    2005-01-01

    A novel multiwall carbon nanotube-chitosan modified electrode has been prepared.The modified electrode resolves the overlapping voltammetric response of dopamine and ascorbic acid into two well-defined peak by 212 mY. The mechanism of discrimination of dopamine from ascorbic acid is discussed. Dopamine can be determined selectively with the carbon nanotube-chitosan modified electrode. The electrode shows good sensitivity, selectivity and stability.keywords: Nanotube-chitosan modified electrode, dopamine, ascorbic acid.

  20. Selection of folate-producing lactic acid bacteria for improving fermented goat milk

    OpenAIRE

    Sanna, Maria Giovanna; Mangia, Nicoletta Pasqualina; Giovanni GARAU; Murgia, Marco Ambrogio; Massa, Tomasina G.; Franco, Mario Andrea; Deiana, Pietrino

    2005-01-01

    Goat milk is a complete food but its low level of folic acid diminisches its nutritional efficacy. In this study, Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus, Lb. delbrueckii subsp. lactis and Lb. helveticus strains were selected for folate production in goat milk to improve its quality. A suitable HPLC method was developed to directly determine both total folate and its biologically active derivatives such as 5-methyl-tetrahydrofolate (5- CH3-H4-PteGlu), tetrah...

  1. Confined Nystatin Polyenes in Nanopore Induce Biologic Ionic Selectivity

    Directory of Open Access Journals (Sweden)

    Khaoula Boukari

    2016-01-01

    Full Text Available Antifungal polyenes such as nystatin (or amphotericin B molecules play an important role in regulating ions permeability through membrane cell. The creation of self-assembled nanopores into the fungal lipid membranes permits the leakage and the selectivity of ions (i.e., blockage of divalent cations that cause the cell death. These abilities are thus of first interest to promote new biomimetic membranes with improved ionic properties. In the present work, we will use molecular dynamic simulations to interpret recent experimental data that showed the transfer of the nystatin action inside artificial nanopore in terms of ion permeability and selectivity. We will demonstrate that nystatin polyenes can be stabilized in a hydrophobic carbon nanotube, even at high concentration. The high potential interaction between the polyenes and the hydrophobic pore wall ensures the apparition of a hole inside the biomimetic nanopore that changes its intrinsic properties. The probability ratios of cation versus anion show interesting reproducibility of experimental measurements and, to a certain extent, opened the way for transferring biological properties in synthetic membranes.

  2. Continuum model for chiral induced spin selectivity in helical molecules

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Ernesto [Centro de Física, Instituto Venezolano de Investigaciones Científicas, 21827, Caracas 1020 A (Venezuela, Bolivarian Republic of); Groupe de Physique Statistique, Institut Jean Lamour, Université de Lorraine, 54506 Vandoeuvre-les-Nancy Cedex (France); Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287 (United States); González-Arraga, Luis A. [IMDEA Nanoscience, Cantoblanco, 28049 Madrid (Spain); Finkelstein-Shapiro, Daniel; Mujica, Vladimiro [Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287 (United States); Berche, Bertrand [Centro de Física, Instituto Venezolano de Investigaciones Científicas, 21827, Caracas 1020 A (Venezuela, Bolivarian Republic of); Groupe de Physique Statistique, Institut Jean Lamour, Université de Lorraine, 54506 Vandoeuvre-les-Nancy Cedex (France)

    2015-05-21

    A minimal model is exactly solved for electron spin transport on a helix. Electron transport is assumed to be supported by well oriented p{sub z} type orbitals on base molecules forming a staircase of definite chirality. In a tight binding interpretation, the spin-orbit coupling (SOC) opens up an effective π{sub z} − π{sub z} coupling via interbase p{sub x,y} − p{sub z} hopping, introducing spin coupled transport. The resulting continuum model spectrum shows two Kramers doublet transport channels with a gap proportional to the SOC. Each doubly degenerate channel satisfies time reversal symmetry; nevertheless, a bias chooses a transport direction and thus selects for spin orientation. The model predicts (i) which spin orientation is selected depending on chirality and bias, (ii) changes in spin preference as a function of input Fermi level and (iii) back-scattering suppression protected by the SO gap. We compute the spin current with a definite helicity and find it to be proportional to the torsion of the chiral structure and the non-adiabatic Aharonov-Anandan phase. To describe room temperature transport, we assume that the total transmission is the result of a product of coherent steps.

  3. Isolation and Fatty Acid Profile of Selected Microalgae Strains from the Red Sea for Biofuel Production

    Directory of Open Access Journals (Sweden)

    Khalid M. Abu-Salah

    2013-05-01

    Full Text Available The isolation of lipid-rich autochthonous strains of microalgae is a crucial stage for the development of a microalgae-based biofuel production plant, as these microalgae already have the necessary adaptations to withstand competition, predation and the temperatures observed at each production site. This is particularly important in extreme climates such as in Saudi Arabia. Resorting to fluorescence activated cell sorting (FACS we screened for and isolated several microalgal strains from samples collected from the Red Sea. Relying on the fluorescence of BODIPY 505/515 (4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diazasindacene and growth performance, four promising candidates were identified and the total lipid content and fatty acid profile was assessed for biofuels production. Selected isolates were classified as chlorophytes, belonging to three different genera: Picochlorum, Nannochloris and Desmochloris. The lipid contents were assessed microscopically by means of BODIPY 505/515-associated fluorescence to detect intracellular lipid bodies, which revealed several lipid drops in all selected strains. This result was confirmed by lipid gravimetric determination, which demonstrated that all strains under study presented inner cell lipid contents ranging from 20% to 25% of the biomass dry weight. Furthermore, the fatty acid methyl esters profile of all strains seems ideal for biodiesel production due to a low degree of polyunsaturated fatty acid methyl esters and high amount of palmitic and oleic acids.

  4. Amplified electrochemical detection of nucleic acid hybridization via selective preconcentration of unmodified gold nanoparticles.

    Science.gov (United States)

    Li, Yuan; Tian, Rui; Zheng, Xingwang; Huang, Rongfu

    2016-08-31

    The common drawback of optical methods for rapid detection of nucleic acid by exploiting the differential affinity of single-/double-stranded nucleic acids for unmodified gold nanoparticles (AuNPs) is its relatively low sensitivity. In this article, on the basis of selective preconcentration of AuNPs unprotected by single-stranded DNA (ssDNA) binding, a novel electrochemical strategy for nucleic acid sequence identification assay has been developed. Through detecting the redox signal mediated by AuNPs on 1, 6-hexanedithiol blocked gold electrode, the proposed method is able to ensure substantial signal amplification and a low background current. This strategy is demonstrated for quantitative analysis of the target microRNA (let-7a) in human breast adenocarcinoma cells, and a detection limit of 16 fM is readily achieved with desirable specificity and sensitivity. These results indicate that the selective preconcentration of AuNPs for electrochemical signal readout can offer a promising platform for the detection of specific nucleic acid sequence. PMID:27506344

  5. Acid-Base Buffering Properties of Five Legumes and Selected Food in vitro

    Directory of Open Access Journals (Sweden)

    Maher M. Al-Dabbas

    2010-01-01

    Full Text Available Problem statement: in vitro acid-Buffering Capacity (BC values of 5% (dry matter aqueous homogenized suspension of five legumes (broad bean, lentils, chickpea, kidney bean and lupine and of selected antacid home preparations (cow's milk, almond, peanut, licorice, carob and lettuce stem were investigated within and among samples from their respective initial pH until pH was decreased to 1.5. BC was the highest for cow's milk, carob, licorice and lettuce stem (BC values 1.65-1.97, intermediate for almond and peanut (BC values, 1.37-1.64 and the lowest for selected legumes (0.84-1.36. Approach: The purpose of this study was to measure in vitro the buffering capacity potential of legumes and other foods commonly used in Jordan as heartburn remedies to determine the ability of these products to de-acidify, neutralize acid, or increase pH levels of an acid and a base solution. Results: BC of the studied legumes showed positive and strong correlations, with protein, aspartic and glutamic amino acids contents (R = 0.95, 0.94, 0.89, respectively and relatively weak correlation with phosphorus content (R = 0.38. Conclusion/Recommendations: The differences in BC within and among studied samples were largely due to the differences in their chemical compositions. Protein, fiber, ash, organic acids and aspartic and glutamic acids contents and alkalinity of ashes showed significant BC, while high fat content in almond and peanut failed to show considerable BC.

  6. Effect of folic acid on prenatal alcohol-induced modification of brain proteome in mice.

    Science.gov (United States)

    Xu, Yajun; Tang, Yunan; Li, Yong

    2008-03-01

    Maternal alcohol consumption during pregnancy can induce central nervous system abnormalities in the fetus, and folic acid supplementation can reverse some of the effects. The objective of the present study was to investigate prenatal alcohol exposure-induced fetal brain proteome alteration and the protective effect of folic acid using proteomic techniques. Alcohol (5.0 g/kg) was given intragastrically from gestational day (GD) 6 to 15, with or without 60.0 mg folic acid/kg given intragastrically during GD 1-16 to pregnant Balb/c mice. The control group received distilled water only. Results of litter evaluation on GD 18 showed that supplementation of folic acid reversed the prevalence of microcephaly induced by alcohol. Proteomic analysis indicated that, under the dosage of the present investigation, folic acid mainly reversed the alcohol-altered proteins involved in energy production, signal pathways and protein translation, which are all important for central nervous system development. PMID:17697403

  7. Pseudomonas putida response in membrane bioreactors under salicylic acid-induced stress conditions.

    Science.gov (United States)

    Collado, Sergio; Rosas, Irene; González, Elena; Gutierrez-Lavin, Antonio; Diaz, Mario

    2014-02-28

    Starvation and changing feeding conditions are frequently characteristics of wastewater treatment plants. They are typical causes of unsteady-state operation of biological systems and provoke cellular stress. The response of a membrane bioreactor functioning under feed-induced stress conditions is studied here. In order to simplify and considerably amplify the response to stress and to obtain a reference model, a pure culture of Pseudomonas putida was selected instead of an activated sludge and a sole substrate (salicylic acid) was employed. The system degraded salicylic acid at 100-1100mg/L with a high level of efficiency, showed rapid acclimation without substrate or product inhibition phenomena and good stability in response to unsteady states caused by feed variations. Under starvation conditions, specific degradation rates of around 15mg/gh were achieved during the adaptation of the biomass to the new conditions and no biofilm formation was observed during the first days of experimentation using an initial substrate to microorganisms ratio lower than 0.1. When substrate was added to the reactor as pulses resulting in rapidly changing concentrations, P. putida growth was observed only for substrate to microorganism ratios higher than 0.6, with a maximum YX/S of 0.5g/g. Biofilm development under changing feeding conditions was fast, biomass detachment only being significant for biomass concentrations on the membrane surface that were higher than 16g/m(2).

  8. Selective serotonin-norepinephrine reuptake inhibitors-induced Takotsubo cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Rahul Vasudev

    2016-01-01

    Full Text Available Context: Takotsubo translates to "octopus pot" in Japanese. Takotsubo cardiomyopathy (TTC is characterized by a transient regional systolic dysfunction of the left ventricle. Catecholamine excess is the one most studied and favored theories explaining the pathophysiology of TTC. Case Report: We present the case of a 52-year-old Hispanic female admitted for venlafaxine-induced TTC with a review literature on all the cases of Serotonin-norepinephrine reuptake inhibitors (SNRI-associated TTC published so far. Conclusion: SNRI inhibit the reuptake of catecholamines into the presynaptic neuron, resulting in a net gain in the concentration of epinephrine and serotonin in the neuronal synapses and causing iatrogenic catecholamine excess, ultimately leading to TTC.

  9. Induced accumulation of oleanolic acid and ursolic acid in cell suspension cultures of Uncaria tomentosa.

    Science.gov (United States)

    Feria-Romero, Iris; Lazo, Elizabeth; Ponce-Noyola, Teresa; Cerda-García-Rojas, Carlos M; Ramos-Valdivia, Ana C

    2005-06-01

    Increasing sucrose from 20 to 50 g l(-1) in Uncaria tomentosa cell suspension cultures enhanced ursolic acid and oleanolic acid production from 129 +/- 61 to 553 +/- 193 microg g(-1) cell dry wt. The maximal concentration of both triterpenes (1680 +/- 39 microg g(-1) cell dry wt) was 8 days after elicitation by jasmonic acid, while yeast extract or citrus pectin treatments produced 1189 +/- 20 or 1120 +/- 26 microg g(-1) cell dry wt, respectively. The ratio of ursolic acid:oleanolic acid was constant at 70:30.

  10. Spatially-Selective Membrane Permeabilization Induced by Cell-Solution Electrode Atmospheric Pressure Plasma Irradiation

    Science.gov (United States)

    Sasaki, Shota; Hokari, Yutaro; Kanzaki, Makoto; Kaneko, Toshiro

    2015-09-01

    Gene transfection, which is the process of deliberately introducing nucleic acids into cells, is expected to play an important role in medical treatment because the process is necessary for gene therapy and creation of induced pluripotent stem (iPS) cells. However, the conventional transfection methods have some problems, so we focus attention on promising transfection methods by atmospheric pressure plasma (APP). We have previously reported that the cell membrane permeability, which is closely related with gene transfection, is improved using a cell-solution electrode for generating He-APP. He-APP is irradiated to the solution containing the adherent cells and delivery materials such as fluorescent dyes (YOYO-1) and plasmid DNA (GFP). In case of YOYO-1 delivery, more than 80% of cells can be transferred only in the plasma-irradiated area and the spatially-selective membrane permeabilization is realized by the plasma irradiation. In addition, it is confirmed that plasmid DNA is transfected and the GFP genes are expressed using same APP irradiation system with no obvious cellular damage.

  11. Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats.

    Science.gov (United States)

    Ateşşahín, Ahmet; Ceríbaşi, Ali Osman; Yuce, Abdurrauf; Bulmus, Ozgür; Cikim, Gürkan

    2007-02-01

    The aim of this study was to investigate the possible protective role of antioxidant treatment with ellagic acid on cisplatin-induced nephrotoxicity using biochemical and histopatological approaches. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in the cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The effects of ellagic acid on cisplatin-induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GSH peroxidase) and catalase activities and histopatological examinations. Administration of cisplatin to rats induced a marked renal failure, characterized by significant increases in plasma creatinine, urea and calcium concentrations. Cisplatin also induced oxidative stress, as indicated by increased kidney tissue concentrations of malondialdehyde, and reduced activities of GSH peroxidase and catalase. Furthermore, treatment with cisplatin caused a marked tubular necrosis, degeneration and desquamation, luminal cast formation, karyomegaly, tubular dilatation, interstitial mononuclear cell infiltration and inter-tubular haemorrhagia. Ellagic acid markedly reduced elevated plasma creatinine, urea and calcium levels and counteracted the deleterious effects of cisplatin on oxidative stress markers. In the same way, ellagic acid ameliorated cisplatin-induced pathological changes including tubular necrosis, degeneration, karyomegaly, tubular dilatation when compared to the cisplatin alone group. These results indicate that the antioxidant ellagic acid might have a protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat, but not enough to inhibit cisplatin-induced renal dysfunction.

  12. Laser-induced isotopic selectivity in the resonance ionization of Os

    OpenAIRE

    Wunderlich, R. K.; Hutcheon, I. D.; Wasserburg, G. J.; Blake, G. A.

    1992-01-01

    Isotope selective effects in resonance ionization mass spectrometry (RIMS) pose a potentially serious limitation to the application of this technique to the precise and reproducible measurement of isotope ratios. In order to identify some of the underlying causes of isotope selectivity in RIMS and to establish procedures for minimizing these effects, we investigated laser-induced isotope selectivity in the resonance ionization of Os. A single-color, one-photon resonant ionization scheme was u...

  13. Nucleoside-nucleotide free diet protects rat colonic mucosa from damage induced by trinitrobenzene sulphonic acid.

    OpenAIRE

    Adjei, A A; Morioka, T.; Ameho, C K; Yamauchi, K.; Kulkarni, A. D.; Al-Mansouri, H M; Kawajiri, A; Yamamoto, S.

    1996-01-01

    BACKGROUND: Growing evidence suggests that intestinal recovery from injury induced by radiation, endotoxin, and protein deficiency is improved by the ingestion of nucleosides and nucleotides. AIM: This study examined the effect of dietary nucleosides and nucleotides supplementation on trinitrobenzene sulphonic acid induced colonic damage in experimental colitis. METHODS: Sprague-Dawley rats were randomised into two groups and fed nucleic acid free 20% casein diet (control) or this diet supple...

  14. Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

    OpenAIRE

    Patel, Snehal S.; Goyal, Ramesh K.

    2011-01-01

    Background: Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. Objective: This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Materials and Methods: Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.). Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o....

  15. Effectiveness of malic acid 1% in patients with xerostomia induced by antihypertensive drugs

    OpenAIRE

    Gómez Moreno, Gerardo; Guardia, Javier; Aguilar Salvatierra, Antonio; Cabrera Ayala, Marible; Maté Sánchez de Val, José Eduardo; Calvo Guirado, José Luis

    2012-01-01

    Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a plac...

  16. Absence of correlation between ACh-induced Ca influx and phosphatidic acid labeling in rat uterus.

    Science.gov (United States)

    Ichida, S; Moriyama, M; Hirooka, Y; Okazaki, Y; Yoshioka, K

    1984-11-27

    Rat uterine smooth muscle was preincubated in Ca-depleted modified Locke-Ringer solution to investigate the correlation between the 32Pi incorporation into phosphatidic acid induced by acetylcholine and the contractile response to acetylcholine induced by the addition of CaCl2 (Ca influx). The results showed that in rat uterine smooth muscle under these conditions phosphatidic acid does not act as a Ca ionophore or as a trigger for opening the Ca channel.

  17. Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

    Science.gov (United States)

    Sanchez, Laura M; Cheng, Andrew T; Warner, Christopher J A; Townsley, Loni; Peach, Kelly C; Navarro, Gabriel; Shikuma, Nicholas J; Bray, Walter M; Riener, Romina M; Yildiz, Fitnat H; Linington, Roger G

    2016-01-01

    Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1) was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection.

  18. Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

    Science.gov (United States)

    Sanchez, Laura M; Cheng, Andrew T; Warner, Christopher J A; Townsley, Loni; Peach, Kelly C; Navarro, Gabriel; Shikuma, Nicholas J; Bray, Walter M; Riener, Romina M; Yildiz, Fitnat H; Linington, Roger G

    2016-01-01

    Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1) was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection. PMID:26992172

  19. Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

    Directory of Open Access Journals (Sweden)

    Laura M Sanchez

    Full Text Available Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1 was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection.

  20. Trifluoroacetic acid as excipient destabilizes melittin causing the selective aggregation of melittin within the centrin-melittin-trifluoroacetic acid complex

    Directory of Open Access Journals (Sweden)

    Belinda Pastrana-Rios

    2015-07-01

    Full Text Available Trifluoroacetic acid (TFA may be the cause of the bottleneck in high resolution structure determination for protein-peptide complexes. Fragment based drug design often involves the use of synthetic peptides which contain TFA (excipient. Our goal was to explore the effects of this excipient on a model complex: centrin-melittin-TFA. We performed Fourier transform infrared, two-dimensional infrared correlation spectroscopies and spectral simulations to analyze the amide I'/I'* band for the components and the ternary complex. Melittin (MLT was observed to have increased helicity upon its interaction with centrin, followed by the thermally induced aggregation of MLT within the ternary complex in the TFA presence.

  1. Cysteamine-induced duodenal ulcer and acid secretion in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1980-01-01

    Duodenal ulcers can be produced in rats within 24 h by a single subcutaneous administration of cysteamine. To determine the role of gastric acid secretion in the pathogenesis of these ulcers, secretory and pathoanatomic studies were performed in chronic fistula rats ater an ulcerogenic dose...... of cysteamine. A prolonged increase of acid secretion was seen after cysteamine, reaching fourfold the basal level after 5 h. The acid response lasted for 10 to 11 h. After vagotomy cysteamine-induced acid secretion was markedly reduced. Ulcer formation was prevented by vagotomy and by drainage of the gastric...... juice before it entered the duodenum. When a gastric acid output equivalent to that produced by the ulcerogenic dose of cysteamine was induced by repeated injections of pentagastrin, no mucosal changes were seen in the duodenum. These results indicate that, although some acid in the duodenum is required...

  2. Kojibiose ameliorates arachidic acid-induced metabolic alterations in hyperglycaemic rats.

    Science.gov (United States)

    Moisés Laparra, José; Díez-Municio, Marina; Javier Moreno, F; Herrero, Miguel

    2015-11-14

    Herein we hypothesise the positive effects of kojibiose (KJ), a prebiotic disaccharide, selected for reducing hepatic expression of inflammatory markers in vivo that could modulate the severity of saturated arachidic acid (ARa)-induced liver dysfunction in hyperglycaemic rats. Animals were fed daily (20 d) with ARa (0·3 mg) together or not with KJ (22 mg approximately 0·5 %, w/w diet). Glucose, total TAG and cholesterol contents and the phospholipid profile were determined in serum samples. Liver sections were collected for the expression (mRNA) of enzymes and innate biomarkers, and intrahepatic macrophage and T-cell populations were analysed by flow cytometry. ARa administration increased the proportion of liver to body weight that was associated with an increased (by 11 %) intrahepatic macrophage population. These effects were ameliorated when feeding with KJ, which also normalised the plasmatic levels of TAG and N-acyl-phosphatidylethenolamine in response to tissue damage. These results indicate that daily supplementation of KJ significantly improves the severity of ARa-induced hepatic alterations. PMID:26344377

  3. Content of amino acids and minerals in selected sorts of legumes

    Directory of Open Access Journals (Sweden)

    Stanislav Kráčmar

    2013-07-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 The aim of this study was to determine amino acid composition and mineral content in selected legume samples. All analyses were carried out at the laboratory temperature of 21±2 °C in triplicate. Amino acid composition was determined using the automatic amino acid analyzer AAA 400 with post-column derivatization. To assess the nutritional value of protein, index of essential amino acids (EAAI was calculated. Minerals were determined using the atomic absorption spectrometer AA 30. All results were statistically evaluated. The highest content of Cys, Glu, Asp, Leu, Lys and Arg was determined in seeds of G. max; only the content of Cys and His was lower than 10 g kg-1. The greatest total content of essential amino acids (EAA was discovered in soybeans, almost 128 g kg-1. The majority (Na, K, Mg, and Ca, trace (Fe, Zn, and Cr and toxic elements (Pb, Cd were determined. Legumes were rich in Mg and Ca-mainly G. max and Ph. vulgaris. The content of Mg was 2.1 g/1000g in soybeans and 1.6 g/1000g in common beans. Also in these two legumes the greatest concentration of toxic Pb was found. Values obtained during the determination of the chemical composition in samples of legumes and buckwheat products can be influenced by many factors, e.g. climatic conditions, location etc.

  4. Selection of dairy culture and changes of Podravec cheese acidity during production

    Directory of Open Access Journals (Sweden)

    Slavko Kirin

    2002-06-01

    Full Text Available The selection and characteristics of dairy culture play a basic role in all types of cheese production process. The most important characteristic is acidification ability i.e. lactic acid formation, which regulates manufacturing and maturing conditions of cheese, thus affecting its organoleptic characteristics as well. In this work the results on control of acidity increase in Podravec cheeseproduction are presented. In the production process, a technical culture as well as identical frozen and concentrated culture, with and without auxiliary Streptococcus thermophilus for direct milk inoculation, were used. It was established that the acidity, expressed as pH value, is more intensively developed in cheeses produced with culture for direct inoculation. This was especially evident in the first phases of production i.e. before cheese salting. During salting the acidity of cheeses, in both cases, was almoust identical. Cheeses produced with identical frozen culture and auxiliary Streptococcus thermophilus culture had more pronounced acidity before salting and lower after salting in comparison with cheeses with the mentioned two cultures. Organoleptic and other characteristics of mature cheeses were identical.

  5. Gene expression in retinoic acid-induced neural tube defects A cDNA mieroarray analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Long; Zhong Yang; Yi Zeng; Hongli Li; Yangyun Han; Chao You

    2009-01-01

    BACKGROUND: Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown.OBJECTIVE: To compare the differences in gene expression between normal embryos and those with neural tube defects.DESIGN, TIME AND SETTING: A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007.MATERIALS: Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group (n = 30) and a normal control group (n =30). The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA.METHODS: Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similady administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic (E) clay 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray.MAIN OUTCOME MEASURES: Morphological changes and differential gene expression between the normal control group and the retinoic acid group.RESULTS: Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of

  6. A micro E-DNA sensor for selective detection of dopamine in presence of ascorbic acid

    Institute of Scientific and Technical Information of China (English)

    朱丹; 李敏; 王丽华; 左小磊

    2015-01-01

    In this paper, a novel method for selectively detection of dopamine (DA) in the interference of ascorbic acid (AA) is described. A nanometer-sized gold flower microelectrode (NGFME) is prepared by flame-etching and electrochemical deposition. The electrode tip was characterized by scanning electron microscope (SEM). The NGFME is sized at about 100 µm and dimensions of thorns of the electrode were in nanometers. By modifying with DA aptamer on the surface, the prepared aptasensor can selectively detect DA even in the presence of high concentration AA. Experimental results show that this NGFME has no response to AA. As a comparison, the carbon fiber electrode without DA aptamer modification is unable to effectively detect DA in the presence of AA. The NGFME is easy-to-prepare, selective and sensitive for DA detection down to 25 µM. The electrode can be expected to detect DA in vivo and in real biological samples.

  7. Oilseed cultivars developed from induced mutations and mutations altering fatty acid composition

    International Nuclear Information System (INIS)

    One hundred and sixty-three cultivars of annual oilseed crops, developed using induced mutations, have been officially approved and released for cultivation in 26 countries. The maximum number of cultivars have been released in soybean (58), followed by groundnut (44), sesame (16), linseed (15), rapeseed (14), Indian mustard (8), castorbean (4), white mustard (3) and sunflower (1). The majority (118 of 163) of the cultivars have been developed as direct mutants and 45 of 163 by using the induced mutants in a crossing programme. While in soybean 53 out of 58 cultivars were selected as direct mutants, in groundnut 22 from 44 were developed after hybridization. Eighty-three cultivars were developed directly by exposing seeds to gamma or X-rays. Attempts have been made to infer the successful dose range, defined as the range which led to the development, registration and release of the maximum number of mutant cultivars for gamma and X-rays. The successful dose ranges in Gy for the main oilseed crops are: soybean 100-200, groundnut 150-250, rapeseed 600-800, Indian mustard 700 and sesame 100-200. The main characteristics of the new cultivars, besides higher yield, are altered plant type, early flowering and maturity and oil content. Mutants altering fatty acid composition have been isolated in soybean, rapeseed, sunflower, linseed and minor oil crops. New cultivars having altered fatty acid composition have been released in rapeseed, sunflower and linseed. The latter, previously grown for non-edible oil, has been converted to a new edible oil crop. (author)

  8. Epoxyeicosatrienoic acids pretreatment improves amyloid β-induced mitochondrial dysfunction in cultured rat hippocampal astrocytes.

    Science.gov (United States)

    Sarkar, Pallabi; Zaja, Ivan; Bienengraeber, Martin; Rarick, Kevin R; Terashvili, Maia; Canfield, Scott; Falck, John R; Harder, David R

    2014-02-15

    Amyloid-β (Aβ) has long been implicated as a causative protein in Alzheimer's disease. Cellular Aβ accumulation is toxic and causes mitochondrial dysfunction, which precedes clinical symptoms of Alzheimer's disease pathology. In the present study, we explored the possible use of epoxyeicosatrienoic acids (EETs), epoxide metabolites of arachidonic acid, as therapeutic target against Aβ-induced mitochondrial impairment using cultured neonatal hippocampal astrocytes. Inhibition of endogenous EET production by a selective epoxygenase inhibitor, MS-PPOH, caused a greater reduction in mitochondrial membrane potential in the presence of Aβ (1, 10 μM) exposure versus absence of Aβ. MS-PPOH preincubation also aggravated Aβ-induced mitochondrial fragmentation. Preincubation of the cells with either 14,15- or 11,12-EET prevented this mitochondrial depolarization and fragmentation. EET pretreatment also further improved the reduction observed in mitochondrial oxygen consumption in the presence of Aβ. Preincubation of the cells with EETs significantly improved cellular respiration under basal condition and in the presence of the protonophore, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP). The uncoupling of ATP synthase from the electron transfer chain that occurred in Aβ-treated cells was also prevented by preincubation with EETs. Lastly, cellular reactive oxygen species production, a hallmark of Aβ toxicity, also showed significant reduction in the presence of EETs. We have previously shown that Aβ reduces EET synthesis in rat brain homogenates and cultured hippocampal astrocytes and neurons (Sarkar P, Narayanan J, Harder DR. Differential effect of amyloid beta on the cytochrome P450 epoxygenase activity in rat brain. Neuroscience 194: 241-249, 2011). We conclude that reduction of endogenous EETs may be one of the mechanisms through which Aβ inflicts toxicity and thus supplementing the cells with exogenous EETs improves mitochondrial dynamics and

  9. Phosphatidic acid inhibits blue light-induced stomatal opening via inhibition of protein phosphatase 1 [corrected].

    Science.gov (United States)

    Takemiya, Atsushi; Shimazaki, Ken-ichiro

    2010-08-01

    Stomata open in response to blue light under a background of red light. The plant hormone abscisic acid (ABA) inhibits blue light-dependent stomatal opening, an effect essential for promoting stomatal closure in the daytime to prevent water loss. However, the mechanisms and molecular targets of this inhibition in the blue light signaling pathway remain unknown. Here, we report that phosphatidic acid (PA), a phospholipid second messenger produced by ABA in guard cells, inhibits protein phosphatase 1 (PP1), a positive regulator of blue light signaling, and PA plays a role in stimulating stomatal closure in Vicia faba. Biochemical analysis revealed that PA directly inhibited the phosphatase activity of the catalytic subunit of V. faba PP1 (PP1c) in vitro. PA inhibited blue light-dependent stomatal opening but did not affect red light- or fusicoccin-induced stomatal opening. PA also inhibited blue light-dependent H(+) pumping and phosphorylation of the plasma membrane H(+)-ATPase. However, PA did not inhibit the autophosphorylation of phototropins, blue light receptors for stomatal opening. Furthermore, 1-butanol, a selective inhibitor of phospholipase D, which produces PA via hydrolysis of phospholipids, diminished the ABA-induced inhibition of blue light-dependent stomatal opening and H(+) pumping. We also show that hydrogen peroxide and nitric oxide, which are intermediates in ABA signaling, inhibited the blue light responses of stomata and that 1-butanol diminished these inhibitions. From these results, we conclude that PA inhibits blue light signaling in guard cells by PP1c inhibition, accelerating stomatal closure, and that PP1 is a cross talk point between blue light and ABA signaling pathways in guard cells.

  10. Pseudomonas putida response in membrane bioreactors under salicylic acid-induced stress conditions

    International Nuclear Information System (INIS)

    Highlights: • MBR under feed-induced stress conditions: starvation and changing feeding conditions. • High capacity of MBR to withstand high variations in feed loads. • Slow biofilm formation under starvation conditions during the first days. • Observed growth of P. putida for substrate to microorganism ratio higher than 0.6 g/g. • Maximum specific growth rate and growth yield values of around 37.5 h−1 and 0.5 g/g. - Abstract: Starvation and changing feeding conditions are frequently characteristics of wastewater treatment plants. They are typical causes of unsteady-state operation of biological systems and provoke cellular stress. The response of a membrane bioreactor functioning under feed-induced stress conditions is studied here. In order to simplify and considerably amplify the response to stress and to obtain a reference model, a pure culture of Pseudomonas putida was selected instead of an activated sludge and a sole substrate (salicylic acid) was employed. The system degraded salicylic acid at 100–1100 mg/L with a high level of efficiency, showed rapid acclimation without substrate or product inhibition phenomena and good stability in response to unsteady states caused by feed variations. Under starvation conditions, specific degradation rates of around 15 mg/g h were achieved during the adaptation of the biomass to the new conditions and no biofilm formation was observed during the first days of experimentation using an initial substrate to microorganisms ratio lower than 0.1. When substrate was added to the reactor as pulses resulting in rapidly changing concentrations, P. putida growth was observed only for substrate to microorganism ratios higher than 0.6, with a maximum YX/S of 0.5 g/g. Biofilm development under changing feeding conditions was fast, biomass detachment only being significant for biomass concentrations on the membrane surface that were higher than 16 g/m2

  11. Pseudomonas putida response in membrane bioreactors under salicylic acid-induced stress conditions

    Energy Technology Data Exchange (ETDEWEB)

    Collado, Sergio; Rosas, Irene; González, Elena; Gutierrez-Lavin, Antonio; Diaz, Mario, E-mail: mariodiaz@uniovi.es

    2014-02-01

    Highlights: • MBR under feed-induced stress conditions: starvation and changing feeding conditions. • High capacity of MBR to withstand high variations in feed loads. • Slow biofilm formation under starvation conditions during the first days. • Observed growth of P. putida for substrate to microorganism ratio higher than 0.6 g/g. • Maximum specific growth rate and growth yield values of around 37.5 h{sup −1} and 0.5 g/g. - Abstract: Starvation and changing feeding conditions are frequently characteristics of wastewater treatment plants. They are typical causes of unsteady-state operation of biological systems and provoke cellular stress. The response of a membrane bioreactor functioning under feed-induced stress conditions is studied here. In order to simplify and considerably amplify the response to stress and to obtain a reference model, a pure culture of Pseudomonas putida was selected instead of an activated sludge and a sole substrate (salicylic acid) was employed. The system degraded salicylic acid at 100–1100 mg/L with a high level of efficiency, showed rapid acclimation without substrate or product inhibition phenomena and good stability in response to unsteady states caused by feed variations. Under starvation conditions, specific degradation rates of around 15 mg/g h were achieved during the adaptation of the biomass to the new conditions and no biofilm formation was observed during the first days of experimentation using an initial substrate to microorganisms ratio lower than 0.1. When substrate was added to the reactor as pulses resulting in rapidly changing concentrations, P. putida growth was observed only for substrate to microorganism ratios higher than 0.6, with a maximum Y{sub X/S} of 0.5 g/g. Biofilm development under changing feeding conditions was fast, biomass detachment only being significant for biomass concentrations on the membrane surface that were higher than 16 g/m{sup 2}.

  12. The Potential Benefits and Adverse Effects of Phytic Acid Supplement in Streptozotocin-Induced Diabetic Rats

    OpenAIRE

    Omoruyi, F. O.; Budiaman, A.; Y. Eng; Olumese, F. E.; Hoesel, J. L.; Ejilemele, A.; Okorodudu, A. O.

    2013-01-01

    In this study, the effect of phytic acid supplement on streptozotocin-induced diabetic rats was investigated. Diabetic rats were fed rodent chow with or without phytic acid supplementation for thirty days. Blood and organ samples were collected for assays. The average food intake was the highest and the body weight gain was the lowest in the group fed phytic acid supplement compared to the diabetic and normal control groups. There was a downward trend in intestinal amylase activity in the gro...

  13. Preventive Effect of Phytic Acid on Isoproterenol-Induced Cardiotoxicity in Wistar Rats

    OpenAIRE

    Brindha, E.; Rajasekapandiyan, M.

    2015-01-01

    This study was aimed to evaluate the preventive role of phytic acid on membrane bound enzymes such as sodium potassium- dependent adenosine triphosphatase (Na+ /K+ ATPase), calcium-dependent adenosine triphosphatase (Ca2+ ATPase) and magnesium- dependent adenosine triphosphatase (Mg2+ ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with phytic acid (25 and 50...

  14. Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36

    OpenAIRE

    Tang Bing; Li; Yang Dachun; Ma Shuangtao; Yang Yongjian

    2011-01-01

    Abstract Background Elevated plasma free fatty acid (FFA) levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36) is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36. Results We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs) treated with oleic acid (OA). We found that OA induces lipid accum...

  15. Selective Aerobic Oxidation of 5-(Hydroxymethyl)furfural to 5-Formyl-2-furancarboxylic Acid in Water.

    Science.gov (United States)

    Ventura, Maria; Aresta, Michele; Dibenedetto, Angela

    2016-05-23

    A simple, cheap, and selective catalyst based on copper/cerium oxides is described for the oxidation of 5-(hydroxymethyl)furfural (5-HMF) in water. An almost quantitative conversion (99 %) with excellent (90 %) selectivity towards the formation of 5-formyl-2-furancarboxylic acid, a platform molecule for other high value chemicals, is observed. The catalyst does not require any pretreatment or additives, such as bases, to obtain high yield and selectivity in water as solvent and using oxygen as oxidant. When a physical mixture of the oxides is used, low conversion and selectivity are observed. Air can be used instead of oxygen, but a lower conversion rate is observed if the same overall pressure is used, and the selectivity remains high. The catalyst can be recovered almost quantitatively and reused. Deactivation of the catalyst, observed in repeated runs, is due to the deposition of humins on its surface. Upon calcination the catalyst almost completely recovers its activity and selectivity, proving that the catalyst is robust. PMID:27101568

  16. Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro by Inducing G1 Arrest and Apoptosis

    Directory of Open Access Journals (Sweden)

    Raja Kumar Vadivelu

    2012-01-01

    Full Text Available Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8 μg/mL significantly (P<0.05. Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC.

  17. Ligand-induced formation of nucleic acid triple helices.

    OpenAIRE

    Pilch, D S; Breslauer, K J

    1994-01-01

    We demonstrate that ligand binding can be used to induce the formation of triplex structures that would not otherwise form. Specifically, we show that binding of berenil or 4',6-diamidino-2-phenylindole DAPI) induces formation of the poly(rA).poly(rA).poly(dT) triplex, providing an example of an RNA(purine).RNA(purine).DNA(pyrimidine) triplex. We also show that binding of berenil, DAPI, ethidium, or netropsin can induce formation of the poly(dT).poly(rA).poly(dT) triplex, thereby overcoming a...

  18. Fatty acid induced remodeling within the human liver fatty acid-binding protein.

    Science.gov (United States)

    Sharma, Ashwani; Sharma, Amit

    2011-09-01

    We crystallized human liver fatty acid-binding protein (LFABP) in apo, holo, and intermediate states of palmitic acid engagement. Structural snapshots of fatty acid recognition, entry, and docking within LFABP support a heads-in mechanism for ligand entry. Apo-LFABP undergoes structural remodeling, where the first palmitate ingress creates the atomic environment for placement of the second palmitate. These new mechanistic insights will facilitate development of pharmacological agents against LFABP. PMID:21757748

  19. Fatty Acid Induced Remodeling within the Human Liver Fatty Acid-binding Protein*

    OpenAIRE

    Sharma, Ashwani; Sharma, Amit

    2011-01-01

    We crystallized human liver fatty acid-binding protein (LFABP) in apo, holo, and intermediate states of palmitic acid engagement. Structural snapshots of fatty acid recognition, entry, and docking within LFABP support a heads-in mechanism for ligand entry. Apo-LFABP undergoes structural remodeling, where the first palmitate ingress creates the atomic environment for placement of the second palmitate. These new mechanistic insights will facilitate development of pharmacological agents against ...

  20. The amelioration effect of tranexamic acid in wrinkles induced by skin dryness.

    Science.gov (United States)

    Hiramoto, Keiichi; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

    2016-05-01

    Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medical amino acid widely used as an anti-inflammatory and a whitening agent. This study examined the effect of tranexamic acid administration in wrinkle formation following skin dryness. We administered tranexamic acid (750mg/kg/day) orally for 20 consecutive days to Naruto Research Institute Otsuka Atrichia (NOA) mice, which naturally develop skin dryness. In these NOA mice, deterioration of transepidermal water loss (TEWL), generation of wrinkles, decrease of collagen type I, and increases in mast cell proliferation and tryptase and matrix metalloproteinase (MMP-1) release were observed. However, these symptoms were improved by tranexamic acid treatment. Moreover, the increase in the β-endorphin level in the blood and the expression of μ-opioid receptor on the surface of fibroblasts increased by tranexamic acid treatment. In addition, when the fibroblasts induced by tranexamic acid treatment were removed, the amelioration effect by tranexamic acid treatment was halved. On the other hand, tranexamic acid treated NOA mice and mast cell removal in tranexamic acid treated NOA mice did not result in changes in the wrinkle amelioration effect. Additionally, the amelioration effect of mast cell deficient NOA mice was half that of tranexamic acid treated NOA mice. These results indicate that tranexamic acid decreased the proliferation of mast cells and increases the proliferation of fibroblasts, subsequently improving wrinkles caused by skin dryness. PMID:27133035

  1. Effect of Marine Omega 3 Fatty Acids on Methylmercury-Induced Toxicity in Fish and Mammalian Cells In Vitro

    Directory of Open Access Journals (Sweden)

    O. J. Nøstbakken

    2012-01-01

    Full Text Available Methylmercury (MeHg is a ubiquitous environmental contaminant which bioaccumulates in marine biota. Fish constitute an important part of a balanced human diet contributing with health beneficial nutrients but may also contain contaminants such as MeHg. Interactions between the marine n-3 fatty acids eicosapentaenoic acid (20:5n-3, EPA and docosahexaenoic acid (22:6n-3, DHA with MeHg-induced toxicity were investigated. Different toxic and metabolic responses were studied in Atlantic salmon kidney (ASK cell line and the mammalian kidney-derived HEK293 cell line. Both cell lines were preincubated with DHA or EPA prior to MeHg-exposure, and cell toxicity was assessed differently in the cell lines by MeHg-uptake in cells (ASK and HEK293, proliferation (HEK293 and ASK, apoptosis (ASK, oxidation of the red-ox probe roGFP (HEK293, and regulation of selected toxicological and metabolic transcriptional markers (ASK. DHA was observed to decrease the uptake of MeHg in HEK293, but not in ASK cells. DHA also increased, while EPA decreased, MeHg-induced apoptosis in ASK. MeHg exposure induced changes in selected metabolic and known MeHg biomarkers in ASK cells. Both DHA and MeHg, but not EPA, oxidized roGFP in HEK293 cells. In conclusion, marine n-3 fatty acids may ameliorate MeHg toxicity, either by decreasing apoptosis (EPA or by reducing MeHg uptake (DHA. However, DHA can also augment MeHg toxicity by increasing oxidative stress and apoptosis when combined with MeHg.

  2. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  3. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    International Nuclear Information System (INIS)

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  4. Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists

    OpenAIRE

    Hayashi, Izumi; Majima, Masataka

    1999-01-01

    Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100 μg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment...

  5. Inhibition of Receptor Interacting Protein Kinases Attenuates Cardiomyocyte Hypertrophy Induced by Palmitic Acid

    OpenAIRE

    Mingyue Zhao; Lihui Lu; Song Lei; Hua Chai; Siyuan Wu; Xiaoju Tang; Qinxue Bao; Li Chen; Wenchao Wu; Xiaojing Liu

    2016-01-01

    Palmitic acid (PA) is known to cause cardiomyocyte dysfunction. Cardiac hypertrophy is one of the important pathological features of PA-induced lipotoxicity, but the mechanism by which PA induces cardiomyocyte hypertrophy is still unclear. Therefore, our study was to test whether necroptosis, a receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3-) dependent programmed necrosis, was involved in the PA-induced cardiomyocyte hypertrophy. We used the PA-treated primary neonatal rat cardi...

  6. [Effect of calcium on medium alkalinization induced by salicylic acid in Salvia miltiorrhiza suspension cultures].

    Science.gov (United States)

    Liu, Liancheng; Wang, Cong; Dong, Juan'e; Su, Hui; Zhuo, Zequn; Xue, Yaxin

    2013-07-01

    We studied medium alkalinization in Salvia miltiorrhiza suspension cultures treated with salicylic acid and the effect of Ca2+ in this process through application of calcium channel antagonists (Verapamil, LaCl3, LiCl, 2-APB) and ionophore A23187. The results show that salicylic acid could induce significant medium alkalinization in S. miltiorrhiza culture. Verapamil and LaCl3 or LiCl and 2-APB, two different groups of calcium channel antagonist, significantly inhibited the medium alkalinization induced by salicylic acid. However, the suppression effect of verapamil or LaCl3 on medium alkalinization induced by salicylic acid was higher than that of LiCl or 2-APB. When two types of calcium channel inhibitor (LaCl3 and 2-APB) were used together, the medium alkalinization induced by salicylic acid was completely suppressed and even reduced the pH in medium. On the other hand, A23187 could promote the medium alkalinization. Based on the results above, we speculated that salicylic acid could induce significant medium alkalinization in S. miltiorrhiza culture, depending on the calcium from both extracell and intracell. Moreover, calcium from extracell plays a more dominant role in this process. Reveal of relationship in this research between Ca2+ and medium alkalinization can provide theory evidence for mechanism of the plant secondary metabolism.

  7. Glucose supplementation-induced changes in the Auxenochlorella protothecoides fatty acid composition suitable for biodiesel production.

    Science.gov (United States)

    Krzemińska, Izabela; Oleszek, Marta

    2016-10-01

    This study evaluates the effect of different concentrations of glucose supplementation on growth, lipid accumulation, and the fatty acid profile in the Auxenochlorella protothecoides. Addition of glucose promoted the growth rate and decreased the chlorophyll content. Compared with photoautotrophic cells, an increase in the lipid content was observed in mixotrophic cells. The glucose addition induced changes in the fatty acid profile. Higher content of saturated fatty acids was found in the case of cells growing in the glucose-free medium. Oleic acid was the predominant component in mixotrophic cells supplemented with 5gL(-1) glucose, while linoleic acids dominated in cultures supplemented with both 1 and 3gL(-1) glucose. The use of glucose was associated with decreased levels of linolenic acid and PUFA. The changes in the fatty acid profile in mixotrophic cells are favourable for biodiesel production. PMID:27485282

  8. Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Zheng Gong

    Full Text Available Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

  9. Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

    Science.gov (United States)

    Gong, Zheng; Tang, M Matt; Wu, Xueliang; Phillips, Nancy; Galkowski, Dariusz; Jarvis, Gary A; Fan, Huizhou

    2016-01-01

    Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

  10. Pattern of aluminum-induced secretion of organic acids differs between rye and wheat.

    Science.gov (United States)

    Li, X F; Ma, J F; Matsumoto, H

    2000-08-01

    Al-Induced secretion of organic acids from the roots has been considered as a mechanism of Al tolerance, but the processes leading to the secretion of organic acids are still unknown. In this study, the secretion pattern and alteration in the metabolism of organic acids under Al stress were examined in rye (Secale cereale L. cv King) and wheat (Triticum aestivum L. cv Atlas 66). Al induced rapid secretion of malate in the wheat, but a lag (6 and 10 h for malic and citric acids, respectively) between the exposure to Al and the secretion of organic acids was observed in the rye. The activities of isocitrate dehydrogenase, phosphoenolpyruvate carboxylase, and malate dehydrogenase were not affected by Al in either plant. The activity of citrate synthase was increased by the exposure to Al in the rye, but not in the wheat. The secretion of malate was not suppressed at low temperature in the wheat, but that of citrate was stopped in the rye. The Al-induced secretion of citrate from roots of the rye was inhibited by the inhibitors of a citrate carrier, which transports citrate from the mitochondria to the cytoplasm. All of these results suggest that alteration in the metabolism of organic acids is involved in the Al-induced secretion of organic acids in rye, but only activation of an anion channel seems to be responsible for the rapid secretion of malate in the wheat.

  11. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Science.gov (United States)

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism.

  12. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Science.gov (United States)

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID:26551768

  13. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance

    DEFF Research Database (Denmark)

    Madsen, Lise; Guerre-Millo, Michéle; Flindt, Esben N;

    2002-01-01

    Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration...... completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA...... that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity....

  14. Direct hepatic differentiation of mouse embryonic stem cells induced by valproic acid and cytokines

    Institute of Scientific and Technical Information of China (English)

    Xue-Jun Dong; Guo-Rong Zhang; Qing-Jun Zhou; Ruo-Lang Pan; Ye Chen; Li-Xin Xiang; Jian-Zhong Shao

    2009-01-01

    AIM: To develop a protocol for direct hepatic lineage differentiation from early developmental progenitors to a population of mature hepatocytes. METHODS: Hepatic progenitor cells and then mature hepatocytes from mouse embryonic stem (ES) cells were obtained in a sequential manner, induced by valproic acid (VPA) and cytokines (hepatocyte growth factor, epidermal growth factor and insulin). Morphological changes of the differentiated cells were examined by phase-contrast microscopy and electron microscopy. Reverse transcription polymerase chain reaction and immunocytochemical analyses were used to evaluate the gene expression profiles of the VPA-induced hepatic progenitors and the hepatic progenitor-derived hepatocytes. Glycogen storage, cytochrome P450 activity, transplantation assay, differentiation of bile duct-like structures and tumorigenic analyses were performed for the functional identification of the differentiated cells. Furthermore, FACS and electron microscopy were used for the analyses of cell cycle profile and apoptosis in VPA-induced hepatic differentiated cells. RESULTS: Based on the combination of VPA and cytokines, mouse ES cells differentiated into a uniform and homogeneous cell population of hepatic progenitor cells and then matured into functional hepatocytes. The progenitor population shared several characteristics with ES cells and hepatic stem/progenitor cells, and represented a novel progenitor cell between ES and hepatic oval cells in embryonic development. The differentiated hepatocytes from progenitor cells shared typical characteristics with mature hepatocytes, including the patterns of gene expression, immunological markers, in vitro hepatocyte functions and in vivo capacity to restore acute-damaged liver function. In addition, the differentiation of hepatic progenitor cells from ES cells was accompanied by significant cell cycle arrest and selective survival of differentiating cells towards hepatic lineages. CONCLUSION: Hepatic cells

  15. Novel ferulic acid esterases from Bifidobacterium sp. produced on selected synthetic and natural carbon sources

    Directory of Open Access Journals (Sweden)

    Dominik Szwajgier

    2010-09-01

    Full Text Available Background. Ferulic acid esterases (or feruloyl esterases, a common group of hydrolases are very well distributed in the plant kongdom. The fungal feruloyl esterases were very extensively studied whereas probiotic lactic acid bacteria as the source of this enzyme were generally omitted. Free phenolic acids – strong antioxidants can be released from the dietary fiber by the action of intestinal lactic acid bacteria. The aim of this study was to examine the three probiotic Bifidobacterium strains to produce extracellular FAE on different synthetic and natural carbon sources. Material and methods. Studies were carried out using Bifidibacteriumstrains (B. animalis Bi30, B. catenulatum KD 14 and B. longum KN 29. The strains were cultivated using minimal growth media containing selected natural and synthetic carbon sources: German wheat bran, rye bran, barley spent grain, isolated larchwood arabinogalactan, apple pectin, corn pectin, methyl esters of phenolic acids. The production of extracellular feruloyl esterase was estimated using the post cultivation supernatants and methyl ferulate. The concentration of ferulic acid released from the ester was determined using HPLC with DAD detection. Results. The most efficient bacterial strain for FAE production was B. animalis cultivated in the presence of methyl p-coumarate and methyl ferulate as the main carbon sources (14.95 nmol·ml-1·min-1 and 4.38 nmol·ml-1·min-1, respectively. In the case of each FAE, the highest activity was obtained at 37oC (pH 6.3 in Theorell/Steinhagen buffer (B. animalis Bi30 or in Tris/HCl buffer (B. catenulatum KD14 and B. longum KN29. Taking under consideration all results, it should be noticed that the highest feruloyl esterase activities were obtained using synthetic methyl esters of phenolic acids. Conclusions. The presented resultsbroaden the knowledgeabout the production of the feruloyl esterase by probiotic bacteria. Although the enzyme is only accessory during

  16. Excitatory amino acid transporter 2 downregulation correlates with thalamic neuronal death following kainic acid-induced status epilepticus in rat.

    Science.gov (United States)

    Sakurai, Masashi; Kurokawa, Haruna; Shimada, Akinori; Nakamura, Kazuhiro; Miyata, Hajime; Morita, Takehito

    2015-02-01

    Recurrent seizures without interictal resumption (status epilepticus) have been reported to induce neuronal death in the midline thalamic region that has functional roles in memory and decision-making; however, the pathogenesis underlying status epilepticus-induced thalamic neuronal death is yet to be determined. We performed histological and immunohistochemical studies as well as cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7 weeks after birth, body weight 250-300 g) treated with intraperitoneal injection of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline solution (n = 20). Histological study using paraffin-embedded specimens revealed neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with calcium deposition in the midline thalamic region of epileptic rats. The distribution of neuronal death was associated with focal loss of immunoreactivity for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for glutamate and increase in number of Iba-1-positive microglial cells showing swollen cytoplasm and long processes. Double immunofluorescence study demonstrated co-expression of interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity in reactive astrocytes. These microglial alterations and astrocytic EAAT2 downregulation were also observed in tissue without obvious neuronal death in kainic acid-treated rats. These results suggest the possible role of glutamate excitotoxicity in neuronal death in the midline thalamic region following kainic acid-induced status epilepticus due to astrocytic EAAT2 downregulation following microglial activation showing upregulation of IL-1β and iNOS.

  17. High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2

    Directory of Open Access Journals (Sweden)

    Hellberg Michael E

    2010-05-01

    Full Text Available Abstract Background Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching. Results In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus, a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella possess proteins structurally similar to tachylectin-2. Conclusions Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1 part of Oculina's innate immunity repertoire, and 2 evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change.

  18. Heme and menaquinone induced electron transport in lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Santos Filipe

    2009-05-01

    Full Text Available Abstract Background For some lactic acid bacteria higher biomass production as a result of aerobic respiration has been reported upon supplementation with heme and menaquinone. In this report, we have studied a large number of species among lactic acid bacteria for the existence of this trait. Results Heme- (and menaquinone stimulated aerobic growth was observed for several species and genera of lactic acid bacteria. These include Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacilllus brevis, Lactobacillus paralimentarius, Streptococcus entericus and Lactococcus garviae. The increased biomass production without further acidification, which are respiration associated traits, are suitable for high-throughput screening as demonstrated by the screening of 8000 Lactococcus lactis insertion mutants. Respiration-negative insertion-mutants were found with noxA, bd-type cytochrome and menaquinol biosynthesis gene-disruptions. Phenotypic screening and in silico genome analysis suggest that respiration can be considered characteristic for certain species. Conclusion We propose that the cyd-genes were present in the common ancestor of lactic acid bacteria, and that multiple gene-loss events best explains the observed distribution of these genes among the species.

  19. Nucleic Acid Analogue Induced Transcription of Double Stranded DNA

    DEFF Research Database (Denmark)

    1998-01-01

    RNA is transcribed from a double stranded DNA template by forming a complex by hybridizing to the template at a desired transcription initiation site one or more oligonucleic acid analogues of the PNA type capable of forming a transcription initiation site with the DNA and exposing the complex to...... displacement of one strand of the DNA locally by the PNA hybridization....

  20. Jasmonic acid induced resistance in grapevines to a root and leaf feeder.

    Science.gov (United States)

    Omer, A D; Thaler, J S; Granett, J; Karban, R

    2000-06-01

    We investigated the effects of induced resistance to the folivore Pacific spider mite, Tetranychus pacificus McGregor (Acari: Tetranychidae), as well as the root-feeding grape phylloxera Daktulosphaira vitifoliae (Fitch) (Homoptera: Phylloxeridae) in grapevines using exogenous applications of the natural plant inducer, jasmonic acid. Foliar jasmonic acid application at concentrations that caused no phytotoxicity significantly reduced the performance of both herbivores. There were less than half as many eggs produced by spider mites feeding on the induced leaves compared with control grapevine leaves. Induction reduced the numbers of phylloxera eggs and nymphal instars by approximately threefold and twofold, respectively, on induced compared with control grapevine roots. The negative demographic effects of jasmonic acid application appeared to be caused by changes in fecundity for the Pacific spider mite, and possibly changes in development rate and fecundity for grape phylloxera. PMID:10902339

  1. Phytosterol, squalene, tocopherol content and fatty acid profile of selected seeds, grains, and legumes.

    Science.gov (United States)

    Ryan, E; Galvin, K; O'Connor, T P; Maguire, A R; O'Brien, N M

    2007-09-01

    The unsaponifiable lipid fraction of plant-based foods is a potential source of bioactive components such as phytosterols, squalene, and tocopherols. The objective of the present study was to determine the levels of phytosterols, and squalene, as well as tocopherols (alpha and beta + gamma) in selected grains, seeds, and legumes. The method comprised acid hydrolysis and lipid extraction followed by alkaline saponification, prior to analysis by HPLC. In addition, the fatty acid profile of the foods was determined via total lipid extraction, fatty acid derivitisation and GC analysis. In general, beta-sitosterol was the most prevalent phytosterol, ranging in concentration from 24.9 mg/100 g in pumpkin seed to 191.4 mg/100 g in peas. Squalene identified in all foods examined in this study, was particularly abundant in pumpkin seed (89.0 mg/100 g). The sum of alpha- and beta+ gamma-tocopherols ranged from 0.1 mg/100 g in rye to 15.9 mg/100 g in pumpkin seeds. Total oil content ranged from 0.9% (w/w) in butter beans to 42.3% (w/w) in pumpkin seed and the type of fat, in all foods examined, was predominantly unsaturated. In conclusion, seeds, grains, and legumes are a rich natural source of phytosterols. Additionally, they contain noticeable amounts of squalene and tocopherols, and in general, their fatty acid profile is favorable. PMID:17594521

  2. Butyric acid production from softwood hydrolysate by acetate-consuming Clostridium sp. S1 with high butyric acid yield and selectivity.

    Science.gov (United States)

    Kim, Minsun; Kim, Ki-Yeon; Lee, Kyung Min; Youn, Sung Hun; Lee, Sun-Mi; Woo, Han Min; Oh, Min-Kyu; Um, Youngsoon

    2016-10-01

    The aim of this work was to study the butyric acid production from softwood hydrolysate by acetate-consuming Clostridium sp. S1. Results showed that Clostridium sp. S1 produced butyric acid by simultaneously utilizing glucose and mannose in softwood hydrolysate and, more remarkably, it consumed acetic acid in hydrolysate. Clostridium sp. S1 utilized each of glucose, mannose, and xylose as well as mixed sugars simultaneously with partially repressed xylose utilization. When softwood (Japanese larch) hydrolysate containing glucose and mannose as the main sugars was used, Clostridium sp. S1 produced 21.17g/L butyric acid with the yield of 0.47g/g sugar and the selectivity of 1 (g butyric acid/g total acids) owing to the consumption of acetic acid in hydrolysate. The results demonstrate potential of Clostridium sp. S1 to produce butyric acid selectively and effectively from hydrolysate not only by utilizing mixed sugars simultaneously but also by converting acetic acid to butyric acid. PMID:27474955

  3. Fatty acid-induced changes in vascular reactivity in healthy adult rats.

    Science.gov (United States)

    Christon, Raymond; Marette, André; Badeau, Mylène; Bourgoin, Frédéric; Mélançon, Sébastien; Bachelard, Hélène

    2005-12-01

    Dietary fatty acids (FAs) are known to modulate endothelial dysfunction, which is the first stage of atherosclerosis. However, their exact role in this initial phase is still unclear. The effects of isolated or combined (by 2) purified FAs from the main FA families were studied on the vascular response of isolated thoracic aorta in healthy rats to get a better understanding of the mechanisms of action of dietary FAs in regulating vascular endothelial function. Cumulative contraction curves to phenylephrine and relaxation curves to carbachol and then to sodium nitroprusside were obtained in the absence or presence of the FAs studied allowing endothelium-dependent and endothelium-independent ability of the smooth muscle to relax to be assessed in each experimental group. The endothelium-dependent vasodilator response to carbachol was lowered by eicosapentaenoic acid, whereas it was not altered either by docosahexaenoic acid alone or by combined eicosapentaenoic acid-docosahexaenoic acid, oleic acid, or stearic acid, and it was increased by linoleic acid (LA). A decreased phenylephrine-induced contraction was observed after incubation with arachidonic acid and with stearic acid. On the other hand, the endothelium-dependent relaxation was reduced by the addition of combined LA-arachidonic acid and LA-oleic acid. In conclusion, these data point out the differential effects of different types of FAs and of FAs alone vs combined on vascular reactivity. The complex nature of these effects could be partially linked to metabolic specificities of endothelial cells and to interactions between some FAs.

  4. Ionizing radiation induced attachment reactions of nucleic acids and their components

    International Nuclear Information System (INIS)

    An extensive bibliographic review is given of experimental and theoretical data on radiation-induced attachment reactions of nucleic acids and their components. Mechanisms of these reactions are reviewed. The reactions with water, formate, and alcohols, with amines and other small molecules, and with radiation sensitizers and nucleic acid-nucleic acid reactions are discussed. Studies of the reaction mechanisms show that many of the reactions occur by radical-molecule reactions, but radical-radical reactions also occur. Radiation modifiers become attached to nucleic acids in vitro and in vivo and there are indications that attachment may be necessary for the action of some sensitizers. (U.S.)

  5. Sinapic Acid and Its Derivatives as Medicine in Oxidative Stress-Induced Diseases and Aging

    Directory of Open Access Journals (Sweden)

    Chunye Chen

    2016-01-01

    Full Text Available Sinapic acid (3,5-dimethoxy-4-hydroxycinnamic acid is an orally bioavailable phytochemical, extensively found in spices, citrus and berry fruits, vegetables, cereals, and oilseed crops and is known to exhibit antioxidant, anti-inflammatory, anticancer, antimutagenic, antiglycemic, neuroprotective, and antibacterial activities. The literature reveals that sinapic acid is a bioactive phenolic acid and has the potential to attenuate various chemically induced toxicities. This minireview is an effort to summarize the available literature about pharmacokinetic, therapeutic, and protective potential of this versatile molecule in health related areas.

  6. Protection of neuroblastoma Neuro2A cells from hypoxia-induced apoptosis by cyclic phosphatidic acid (cPA.

    Directory of Open Access Journals (Sweden)

    Mari Gotoh

    Full Text Available Cyclic phosphatidic acid (cPA is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We have previously shown that cPA significantly suppresses ischemia-induced delayed neuronal death and the accumulation of glial fibrillary acidic protein in the CA1 region of the rat hippocampus. These results indicated that the systemic administration of cPA can protect hippocampal neurons against ischemia-induced delayed neuronal cell death. In the current study, we investigated the effects of cPA on neuronal cell death caused by hypoxia in vitro and the molecular mechanisms underlying these effects. We used cobalt chloride (CoCl(2 to expose cells to hypoxic conditions in vitro. Treating mouse neuroblastoma (Neuro2A cells with CoCl(2 induced nuclear DNA condensation and phosphatidylserine exposure. However, adding cPA led to the suppression of CoCl(2-induced apoptosis in a cPA dose-dependent manner and attenuated the increase in the Bax/Bcl-2 ratio caused by CoCl(2. Quantitative PCR analysis showed that Neuro2A cells strongly express the LPA(1, LPA(2, and LPA(6, which are G-protein coupled receptors that can be activated by cPA. To date, LPA(1 and LPA(2 have been reported to exhibit antiapoptotic activity. Therefore, to assess the roles of LPA(1 and LPA(2 on cPA-induced neuroprotective functions, Ki16425, a selective LPA(1 and LPA(3 antagonist, was adopted to know the LPA(1 function and siRNA was used to knockdown the expression of LPA(2. On the basis of our results, we propose that cPA-induced protection of Neuro2A cells from CoCl(2-induced hypoxia damage is mediated via LPA(2.

  7. Bile acid-induced virulence gene expression of Vibrio parahaemolyticus reveals a novel therapeutic potential for bile acid sequestrants.

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Gotoh

    Full Text Available Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2 encoded in pathogenicity island (Vp-PAI is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections.

  8. Stromelysin-3 induction and interstitial collagenase repression by retinoic acid. Therapeutical implication of receptor-selective retinoids dissociating transactivation and AP-1-mediated transrepression.

    Science.gov (United States)

    Guérin, E; Ludwig, M G; Basset, P; Anglard, P

    1997-04-25

    Human stromelysin-3 and interstitial collagenase are matrix metalloproteinases whose expression by stromal cells in several types of carcinomas has been associated with cancer progression. We compared here the regulation of the expression of both proteinases by retinoids in human fibroblasts. Physiological concentrations of retinoic acid were found to simultaneously induce stromelysin-3 and repress interstitial collagenase. In both cases, the involvement of a transcriptional mechanism was supported by run-on assays. Furthermore, in transient transfection experiments, the activity of the stromelysin-3 promoter was induced by retinoic acid through endogenous receptors acting on a DR1 retinoic acid-responsive element. The ligand-dependent activation of the receptors was also investigated by using selective synthetic retinoids, and we demonstrated that retinoic acid-retinoid X receptor heterodimers were the most potent functional units controlling both stromelysin-3 induction and interstitial collagenase repression. However, specific retinoids dissociating the transactivation and the AP-1-mediated transrepression functions of the receptors were found to repress interstitial collagenase without inducing stromelysin-3. These findings indicate that such retinoids may represent efficient inhibitors of matrix metalloproteinase expression in the treatment of human carcinomas. PMID:9111003

  9. How to distinguish conformational selection and induced fit based on chemical relaxation rates

    CERN Document Server

    Paul, Fabian

    2016-01-01

    Protein binding often involves conformational changes. Important questions are whether a conformational change occurs prior to a binding event ('conformational selection') or after a binding event ('induced fit'), and how conformational transition rates can be obtained from experiments. In this article, we present general results for the chemical relaxation rates of conformational-selection and induced-fit binding processes that hold for all concentrations of proteins and ligands and, thus, go beyond the standard pseudo-first-order approximation of large ligand concentration. These results allow to distinguish conformational-selection from induced-fit processes - also in cases in which such a distinction is not possible under pseudo-first-order conditions - and to extract conformational transition rates of proteins from chemical relaxation data.

  10. Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats.

    Science.gov (United States)

    Khairnar, Upasana; Upaganlawar, Aman; Upasani, Chandrashekhar

    2016-01-01

    Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200-250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats. PMID:27418998

  11. Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Upasana Khairnar

    2016-01-01

    Full Text Available Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200–250 g were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o., ascorbic acid (40 mg/kg/day, p.o., and combination of protocatechuic acid (20 mg/kg/day, p.o. and ascorbic acid (20 mg/kg/day, p.o. followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content, tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content, and membrane bound phosphatase (ATPase compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.

  12. Structural plasticity and dynamic selectivity of acid sensing ion channel–toxin complexes

    OpenAIRE

    Baconguis, Isabelle; Gouaux, Eric

    2012-01-01

    Acid sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels implicated in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non- and sodium-selective currents in chicken ASIC1a at pH 7.25 and 5.5, respectively. Crystal structures of ASIC1a – psalmotoxin complexes map the toxin binding site to the extracell...

  13. N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands

    DEFF Research Database (Denmark)

    Clausen, Rasmus Prætorius; Christensen, Caspar; Hansen, Kasper Bø;

    2008-01-01

    glycine (NHP5G) derivatives are selectively recognized by N-methyl- d-aspartic acid (NMDA) receptors and that the ( R)-enantiomers are preferred. Moreover, several of the compounds are able to discriminate between individual subtypes among the NMDA receptors, providing new pharmacological tools. For......A series of analogues based on N-hydroxypyrazole as a bioisostere for the distal carboxylate group of aspartate have been designed, synthesized, and pharmacologically characterized. Affinity studies on the major glutamate receptor subgroups show that these 4-substituted N-hydroxypyrazol-5-yl...

  14. Selection of oleuropein-degrading lactic acid bacteria strains isolated from fermenting Moroccan green olives

    Energy Technology Data Exchange (ETDEWEB)

    Ghabbour, N.; Lamzira, Z.; Thonart, P.; Cidalia, P.; Markaouid, M.; Asehraoua, A.

    2011-07-01

    A total of 177 strains of lactic acid bacteria (LAB) were isolated from early-stage Moroccan Picholine green olive fermentation, including Lactobacillus plantarum (44.63%), Lactobacillus pentosus (25.99%), Lactobacillus brevis (9.61%) and Pediococcus pentosaceus (19.77%). All the isolates were screened for their tolerance to olive leaf extract and oleuropein. Most of the isolates (85.3%) were found able to degrade oleuropein, when evaluated by either oleuropein or 5-Bromo-4-chloro-3-indolyl {beta}-D-glucuronide (X-Gluc) as substrates. The biodegradation capacity of the selected strains of each species was confirmed by HPLC analysis. (Author).

  15. CHANGES IN SELECTIVITY OF GAMMA-AMINOBUTYRIC ACID FORMATION EFFECTED BY FERMENTATION CONDITIONS AND MICROORGANISMS RESOURCES

    OpenAIRE

    Kamila Kovalovská; Róbert Mazur; Jozef Hudec

    2011-01-01

    In this study we observe the effect of fermentation conditions and resources of microorganisms for production of γ-aminobutyric acid (GABA). The content of produced GABA depends on various conditions such as the amount of precursor, an addition of salt, enzyme and the effect of pH. The highest selectivity of GABA (74.0 %) from the precursor (L-monosodium glutamate) has been determinate in the follow conditions: in the presence of pre-cultured microorganisms from Encián cheese in amount 1.66 %...

  16. Selective Michael-type addition of a D-glucuronic acid derivative in the synthesis of model substances for uronic acid containing polysaccharides

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available A flexible protocol for the preparation of model substances for uronic acid containing polysaccharides is presented. We have synthesized a D-glucuronic acid derivative which is designed so that it easily can be conjugated with different structures and architectures by selective Michael-type addition. By successful coupling of the glucuronic acid derivative to polyethylene glycol with high degree of conversion, products were obtained that were easily characterized and which resembled polysaccharides in terms of solubility and purification methods that could be employed. The model substance can potentially be used to facilitate optimization of low-degree modification reactions of high molecular weight D-glucuronic acid containing polysaccharides.

  17. Selective oxidation of glycerol to formic acid in highly concentrated aqueous solutions with molecular oxygen using V-substituted phosphomolybdic acids

    KAUST Repository

    Zhang, Jizhe

    2014-01-01

    Formic acid is an important commodity chemical as well as a promising medium for hydrogen storage and hydrogen production. In this paper, we report that formic acid can be produced through selective oxidation of glycerol, a low-cost by-product of biodiesel, by using vanadium-substituted phosphomolybdic acids as catalysts and molecular oxygen as the oxidant. Significantly, this catalytic system allows for high-concentration conversions and thus leads to exceptional efficiency. Specifically, 3.64 g of formic acid was produced from 10 g of glycerol/water (50/50 in weight) solution. © 2014 the Partner Organisations.

  18. Effects of receptor-selective retinoids on CYP26 gene expression and metabolism of all-trans-retinoic acid in intestinal cells.

    Science.gov (United States)

    Lampen, A; Meyer, S; Nau, H

    2001-05-01

    Retinoids mediate most of their function via interaction with retinoid receptors [retinoic acid receptors (RARs) and retinoid X receptors (RXRs)], which act as ligand-activated transcription factors controlling the expression of a number of target genes. The complex mechanistic pattern of retinoid-induced effects on gene expression of CYP26 and intestinal metabolism of all-trans-retinoic acid (RA) was investigated here by studying the effects of retinoid ligands with relative selectivity for binding and transactivation of the retinoid acid receptors, RARs and RXRs, in human intestinal Caco-2 cells. We show here that CYP26 is expressed in human duodenum and colon. In Caco-2 cells not only all-trans-RA but also synthetic agonists of the RAR induced intestinal CYP26 gene expression and all-trans-RA metabolism as well. The RARalpha ligand Am580 induced the CYP26 gene expression more than the RARbeta ligand CD2019 or the RARgamma ligand CD437 suggesting the highest specificity for RARalpha on intestinal CYP26 gene regulation. RXR ligands alone did not induce CYP26 gene expression or RA metabolism in Caco-2 cells at all. But together with the RARalpha ligand, Am580, there were enhanced effects on the induction of CYP26 gene expression and on the induction of the metabolism of all-trans-RA. We conclude that gene regulation of CYP26 and the metabolism of all-trans-RA in intestinal cells is regulated through RXR and RAR heterodimerization. When coadministered, RAR agonists showed the highest potency for CYP26 gene regulation. Receptor-selective retinoids showed enhanced effects on induction of CYP26 gene expression and all-trans-retinoic acid metabolism.

  19. Sequence-selective targeting of duplex DNA by peptide nucleic acids

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2010-01-01

    Sequence-selective gene targeting constitutes an attractive drug-discovery approach for genetic therapy, with the aim of reducing or enhancing the activity of specific genes at the transcriptional level, or as part of a methodology for targeted gene repair. The pseudopeptide DNA mimic peptide...... nucleic acid (PNA) can recognize duplex DNA with high sequence specificity and affinity in triplex, duplex and double-duplex invasive modes or non-invasive triplex modes. Novel PNA modification has improved the affinity for DNA recognition via duplex invasion, double-duplex invasion and triplex...... recognition considerably. Such modifications have also resulted in new approaches to targeted gene repair and sequence-selective double-strand cleavage of genomic DNA....

  20. Characterization and Design of Zeolite Catalysts Solid Acidity, Shape Selectivity and Loading Properties

    CERN Document Server

    Niwa, Miki; Okumura, Kazu

    2010-01-01

    Zeolites are microporous, aluminosilicate minerals commonly used as commercial adsorbents. Zeolite-based catalysts are used by industrial chemical companies in the interconversion of hydrocarbons and the alkylation of aromatic compounds. The current book deals with the characterization of specific properties of Zeolites and calculations for the design of catalysts. Measurements and utilization of solid acidity, shape selectivity, and loading properties, that are three prominent properties of a Zeolite catalyst, are treated in detail. These features concern chemical vapor deposition of silica, shape selectivity, loading properties, solid activity, Brønsted or Lewis character, ammonia temperature programmed desorption, control of the pore-opening size by chemical vapor deposition of silica and XAFS analysis of metals being highly dispersed inside and outside a framework.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Selective inhibition of intra-alveolar p55 TNF receptor attenuates ventilator-induced lung injury

    OpenAIRE

    Bertok, Szabolcs; Wilson, Michael R.; Morley, Peter J.; de Wildt, Ruud; Bayliffe, Andrew; Takata, Masao

    2011-01-01

    Background Tumour necrosis factor (TNF) is upregulated in the alveolar space early in the course of ventilator-induced lung injury (VILI). Studies in genetically modified mice indicate that the two TNF receptors play opposing roles during injurious high-stretch mechanical ventilation, with p55 promoting but p75 preventing pulmonary oedema. Aim To investigate the effects of selective inhibition of intra-alveolar p55 TNF receptor on pulmonary oedema and inflammation during ventilator-induced lu...

  3. Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes

    OpenAIRE

    Wu, I; Shin, S. C.; Cao, Y; Bender, I K; N Jafari; Feng, G.; Lin, S.; Cidlowski, J. A.; Schleimer, R. P.; Lu, N Z

    2013-01-01

    Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expres...

  4. Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury

    OpenAIRE

    Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G.; Choudhry, Mashkoor A.; Raju, Raghavan; Bland, Kirby I.; Chaudry, Irshad H.

    2008-01-01

    Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of pro...

  5. Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.

    Science.gov (United States)

    Martínez, Laura; Torres, Sandra; Baulies, Anna; Alarcón-Vila, Cristina; Elena, Montserrat; Fabriàs, Gemma; Casas, Josefina; Caballeria, Joan; Fernandez-Checa, Jose C; García-Ruiz, Carmen

    2015-12-01

    Palmitic acid (PA) induces hepatocyte apoptosis and fuels de novo ceramide synthesis in the endoplasmic reticulum (ER). Myristic acid (MA), a free fatty acid highly abundant in copra/palmist oils, is a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Here we investigated the synergism between MA and PA in ceramide synthesis, ER stress, lipotoxicity and NASH. Unlike PA, MA is not lipotoxic but potentiated PA-mediated lipoapoptosis, ER stress, caspase-3 activation and cytochrome c release in primary mouse hepatocytes (PMH). Moreover, MA kinetically sustained PA-induced total ceramide content by stimulating dehydroceramide desaturase and switched the ceramide profile from decreased to increased ceramide 14:0/ceramide16:0, without changing medium and long-chain ceramide species. PMH were more sensitive to equimolar ceramide14:0/ceramide16:0 exposure, which mimics the outcome of PA plus MA treatment on ceramide homeostasis, than to either ceramide alone. Treatment with myriocin to inhibit ceramide synthesis and tauroursodeoxycholic acid to prevent ER stress ameliorated PA plus MA induced apoptosis, similar to the protection afforded by the antioxidant BHA, the pan-caspase inhibitor z-VAD-Fmk and JNK inhibition. Moreover, ruthenium red protected PMH against PA and MA-induced cell death. Recapitulating in vitro findings, mice fed a diet enriched in PA plus MA exhibited lipodystrophy, hepatosplenomegaly, increased liver ceramide content and cholesterol levels, ER stress, liver damage, inflammation and fibrosis compared to mice fed diets enriched in PA or MA alone. The deleterious effects of PA plus MA-enriched diet were largely prevented by in vivo myriocin treatment. These findings indicate a causal link between ceramide synthesis and ER stress in lipotoxicity, and imply that the consumption of diets enriched in MA and PA can cause NASH associated with lipodystrophy.

  6. Genetic parameters for rennet- and acid-induced coagulation properties in milk from Swedish Red dairy cows.

    Science.gov (United States)

    Gustavsson, F; Glantz, M; Poulsen, N A; Wadsö, L; Stålhammar, H; Andrén, A; Lindmark Månsson, H; Larsen, L B; Paulsson, M; Fikse, W F

    2014-01-01

    Milk coagulation is an important processing trait, being the basis for production of both cheese and fermented products. There is interest in including technological properties of these products in the breeding goal for dairy cattle. The aim of the present study was therefore to estimate genetic parameters for milk coagulation properties, including both rennet- and acid-induced coagulation, in Swedish Red dairy cattle using genomic relationships. Morning milk samples and blood samples were collected from 395 Swedish Red cows that were selected to be as genetically unrelated as possible. Using a rheometer, milk samples were analyzed for rennet- and acid-induced coagulation properties, including gel strength (G'), coagulation time, and yield stress (YS). In addition to the technological traits, milk composition was analyzed. A binary trait was created to reflect that milk samples that had not coagulated 40min after rennet addition were considered noncoagulating milk. The cows were genotyped by using the Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers remained after quality control and were used to construct a matrix of genomic relationships among the cows. Multivariate models including fixed effects of herd, lactation stage, and parity were fitted using the ASReml software to obtain estimates of heritabilities and genetic and phenotypic correlations. Heritability estimates (h(2)) for G' and YS in rennet and acid gels were found to be high (h(2)=0.38-0.62) and the genetic correlations between rennet-induced and acid-induced coagulation properties were weak but favorable, with the exception of YSrennet with G'acid and YSacid, both of which were strong. The high heritability (h(2)=0.45) for milk coagulating ability expressed as a binary trait suggests that noncoagulation could be eliminated through breeding. Additionally, the results indicated that the current breeding objective could increase the frequency of noncoagulating milk and

  7. In vitro selection of induced mutants to salt-tolerance: Inducible gene regulation for salt tolerance

    International Nuclear Information System (INIS)

    A selection protocol to obtain salt tolerant calli, followed by regeneration and progeny-test of the regenerated plants for salt tolerance in rice was investigated. Callus cultures were initiated from salt-sensitive US elite rice lines and cv. 'Pokkali'. Salt-tolerant cell lines were selected from these by a single step selection procedure. The selected salt-tolerant lines grew well on medium with ± 0.5% or 1% NaCl, while the parent lines occasionally survived, but did not grow at these salt concentrations. Plants were regenerated from these cell lines through different passages on medium containing salt. Seed was collected from the regenerated plants and salt tolerance of R2 seedlings was compared with those regenerated without salt selection. Salt-tolerance was measured by survival and productive growth of newly germinated seedlings in Hoagland solution with 0.3% and 0.5% NaCl for 4 weeks. Heritable improvement in salt tolerance was obtained in R2 seedlings from one plant regenerated after 5 months selection. Survival and growth of these seedlings was equivalent to that from 'Pokkali' seedlings. These results show that cellular tolerance can provide salt-tolerance in rice plants. (author). 6 refs, 2 tabs

  8. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.

    Science.gov (United States)

    Tunaru, Sorin; Althoff, Till F; Nüsing, Rolf M; Diener, Martin; Offermanns, Stefan

    2012-06-01

    Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP(3) prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects.

  9. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

    Directory of Open Access Journals (Sweden)

    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  10. Salicylic acid and gentisic acid induce RNA silencing-related genes and plant resistance to RNA pathogens.

    Science.gov (United States)

    Campos, Laura; Granell, Pablo; Tárraga, Susana; López-Gresa, Pilar; Conejero, Vicente; Bellés, José María; Rodrigo, Ismael; Lisón, Purificación

    2014-04-01

    We have observed that treatments with salicylic acid (SA) or gentisic acid (GA) induced resistance to RNA pathogens such as ToMV and CEVd in tomato and Gynura auriantiaca, respectively. Accumulation of SA and GA has been found to occur in plants infected by these pathogens, thus pointing out a possible defence role of both molecules. To study the molecular basis of the observed induced resistance to RNA pathogens the induction of silencing-related genes by SA and GA was considered. For that purpose, we searched for tomato genes which were orthologous to those described in Arabidopsis thaliana, such as AtDCL1, AtDCL2, AtDCL4, AtRDR1, AtRDR2 and AtRDR6, and we tracked their induction in tomato along virus and viroid infections. We observed that CEVd significantly induced all these genes in tomato, with the exception of ToRDR6, being the induction of ToDCL4 the most outstanding. Regarding the ToMV asymptomatic infection, with the exception of ToRDR2, we observed a significant induction of all the indicated silencing-related genes, being ToDCL2 the most induced gene. Subsequently, we analyzed their transcriptional activation by SA and at the time when ToMV was inoculated on plants. ToDCL2, ToRDR1 and ToRDR2 were significantly induced by both SA and GA, whereas ToDCL1 was only induced by SA. Such an induction resulted more effective by SA treatment, which is in agreement with the stronger SA-induced resistance observed. Our results suggest that the observed delay in the RNA pathogen accumulation could be due to the pre-induction of RNA silencing-related genes by SA or GA.

  11. Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes

    Energy Technology Data Exchange (ETDEWEB)

    Baconguis, Isabelle; Gouaux, Eric [Oregon HSU

    2012-07-29

    Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na+-selective currents in chicken ASIC1a at pH7.25 and 5.5, respectively. Crystal structures of ASIC1a–psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH7.25 the pore is approximately 10Å in diameter, whereas at pH5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7Å, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.

  12. Selection of suitable mineral acid and its concentration for biphasic dilute acid hydrolysis of the sodium dithionite delignified Prosopis juliflora to hydrolyze maximum holocellulose.

    Science.gov (United States)

    Naseeruddin, Shaik; Desai, Suseelendra; Venkateswar Rao, L

    2016-02-01

    Two grams of delignified substrate at 10% (w/v) level was subjected to biphasic dilute acid hydrolysis using phosphoric acid, hydrochloric acid and sulfuric acid separately at 110 °C for 10 min in phase-I and 121 °C for 15 min in phase-II. Combinations of acid concentrations in two phases were varied for maximum holocellulose hydrolysis with release of fewer inhibitors, to select the suitable acid and its concentration. Among three acids, sulfuric acid in combination of 1 & 2% (v/v) hydrolyzed maximum holocellulose of 25.44±0.44% releasing 0.51±0.02 g/L of phenolics and 0.12±0.002 g/L of furans, respectively. Further, hydrolysis of delignified substrate using selected acid by varying reaction time and temperature hydrolyzed 55.58±1.78% of holocellulose releasing 2.11±0.07 g/L and 1.37±0.03 g/L of phenolics and furans, respectively at conditions of 110 °C for 45 min in phase-I & 121 °C for 60 min in phase-II.

  13. Modular Attachment of Appended Boron Lewis Acids to a Ruthenium Pincer Catalyst: Metal-Ligand Cooperativity Enables Selective Alkyne Hydrogenation.

    Science.gov (United States)

    Tseng, Kuei-Nin T; Kampf, Jeff W; Szymczak, Nathaniel K

    2016-08-24

    A new series of bifunctional Ru complexes with pendent Lewis acidic boranes were prepared by late-stage modification of an active hydrogen-transfer catalyst. The appended boranes modulate the reactivity of a metal hydride as well as catalytic hydrogenations. After installing acidic auxiliary groups, the complexes become multifunctional and catalyze the cis-selective hydrogenation of alkynes with higher rates, conversions, and selectivities compared with the unmodified catalyst. PMID:27472301

  14. Eicosapentaenoic Acid Protects against Palmitic Acid-Induced Endothelial Dysfunction via Activation of the AMPK/eNOS Pathway

    Directory of Open Access Journals (Sweden)

    Che-Hsin Lee

    2014-06-01

    Full Text Available Recent studies have shown that free fatty acids are associated with chronic inflammation, which may be involved in vascular injury. The intake of eicosapentaenoic acid (EPA can decrease cardiovascular disease risks, but the protective mechanisms of EPA on endothelial cells remain unclear. In this study, primary human umbilical vein endothelial cells (HUVECs treated with palmitic acid (PA were used to explore the protective effects of EPA. The results revealed that EPA attenuated PA-induced cell death and activation of apoptosis-related proteins, such as caspase-3, p53 and Bax. Additionally, EPA reduced the PA-induced increase in the generation of reactive oxygen species, the activation of NADPH oxidase, and the upregulation of inducible nitric oxide synthase (iNOS. EPA also restored the PA-mediated reduction of endothelial nitric oxide synthase (eNOS and AMP-activated protein kinase (AMPK phosphorylation. Using AMPK siRNA and the specific inhibitor compound C, we found that EPA restored the PA-mediated inhibitions of eNOS and AKT activities via activation of AMPK. Furthermore, the NF-κB signals that are mediated by p38 mitogen-activated protein kinase (MAPK were involved in protective effects of EPA. In summary, these results provide new insight into the possible molecular mechanisms by which EPA protects against atherogenesis via the AMPK/eNOS-related pathway.

  15. Polyunsaturated fatty acids in the blood of spontaneously or induced muricidal male Wistar rats.

    Science.gov (United States)

    Augier, S; Penes, M C; Debilly, G; Miachon, A S

    2003-04-15

    Serum levels of several n-6 and n-3 polyunsaturated fatty acids were compared in male Wistar muricidal (Mu) and non-Mu rats. The Mu behavior was either spontaneous or induced by long-term isolation, feeding with a starch-enriched polyunsaturated fatty acid diet (PUFA+S), water restriction, or adrenalectomy (ADX). Arachidonic acid (ARA) levels were lower in diet-induced (PUFA+S) Mu rats than in their non-Mu controls. Total n-6 fatty acid levels were also lower in spontaneously Mu rats than in spontaneously non-Mu rats. Docosahexaenoic acid (DHA) and total n-3 fatty acids levels were lower in rats with isolation-induced Mu behavior. The n-3/n-6 ratio was higher in spontaneously Mu rats than in spontaneously non-Mu rats. The changes in ARA levels were greater than those in DHA levels, possibly due to the higher blood-brain barrier passage of arachidonic acid. The results were analyzed in the light of recent results showing a role of PUFAs in human and animal behavior. PMID:12725904

  16. G-quadruplex DNAzymes-induced highly selective and sensitive colorimetric sensing of free heme in rat brain.

    Science.gov (United States)

    Li, Ruimin; Jiang, Qin; Cheng, Hanjun; Zhang, Guoqiang; Zhen, Mingming; Chen, Daiqin; Ge, Jiechao; Mao, Lanqun; Wang, Chunru; Shu, Chunying

    2014-04-21

    Direct selective determination of free heme in the cerebral system is of great significance due to the crucial roles of free heme in physiological and pathological processes. In this work, a G-quadruplex DNAzymes-induced highly sensitive and selective colorimetric sensing of free heme in rat brain is established. Initially, the conformation of an 18-base G-rich DNA sequence, PS2.M (5'-GTGGGTAGGGCGGGTTGG-3'), in the presence of K(+), changes from a random coil to a "parallel" G-quadruplex structure, which can bind free heme in the cerebral system with high affinity through π-π stacking. The resulted heme/G-quadruplex complex exhibits high peroxidase-like activity, which can be used to catalyze the oxidation of colorless ABTS(2-) to green ABTS˙(-) by H2O2. The concentration of heme can be evaluated by the naked eye and determined by UV-vis spectroscopy. The signal output showed a linear relationship for heme within the concentration range from 1 to 120 nM with a detection limit of 0.637 nM. The assay demonstrated here was highly selective and free from the interference of physiologically important species such as dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbate acid (AA), cysteine, uric acid (UA), glucose and lactate in the cerebral system. The basal dialysate level of free heme in the microdialysate from the striatum of adult male Sprague-Dawley rats was determined to be 32.8 ± 19.5 nM (n = 3). The analytic protocol possesses many advantages, including theoretical simplicity, low-cost technical and instrumental demands, and responsible detection of heme in rat brain microdialysate.

  17. Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

    OpenAIRE

    Yoshihiro Akimoto; Mary Miyaji; Riyo Morimoto-Kamata; Yasuhiro Kosaka; Akiko Obinata

    2014-01-01

    Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488). However, the molecular mechanism of this tra...

  18. Nanosized SnO2 Particles Dispersed on a Graphite Electrode for Selective Detection of Dopamine and Ascorbic Acid

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A novel nano-SnO2/graphite electrode has been prepared via polishing procedure to produce active and stable surface. The modified electrode resolves the overlapping voltammetric response of dopamine and ascorbic acid into two well-defined peaks by 230 mV. The mechanism of discrimination of dopamine from ascorbic acid is discussed. Dopamine and ascorbic acid can be determined simultaneously with the modified electrode. The electrode shows good sensitivity, selectivity and stability.

  19. Dietary amino acid-induced systemic lupus erythematosus.

    Science.gov (United States)

    Montanaro, A; Bardana, E J

    1991-05-01

    The effects of dietary manipulations on autoimmune disease are understood poorly. In this article, we detail our experience with a human subject who developed autoimmune hemolytic anemia while participating in a research study that required the ingestion of alfalfa seeds. Subsequent experimental studies in primates ingesting alfalfa sprout seeds and L-canavanine (a prominent amino acid constituent of alfalfa) is presented. The results of these studies indicate a potential toxic and immunoregulatory role of L-canavanine in the induction of a systemic lupus-like disease in primates. PMID:1862241

  20. The Radiation Induced Graft Copolymerization of Methacrylic Acid to Nylon

    International Nuclear Information System (INIS)

    The grafting of methacrylic acid to nylon by the preirradiation technique has been studied. The rate of grafting is appreciably larger than that of homopolymerization. No simple relation exists between reaction rate and total dose. The temperature dependence of the rate of grafting to the fibre, preirradiated in air, indicates that initiation of grafting is likely to take place by decomposition of peroxide groups formed on irradiation. Electrical resistance measurements on the irradiated fibre indicate that this has been reduced by a factor of 10. (author)

  1. Novel 3,4-seco bile acid diamides as selective anticancer proliferation and migration agents.

    Science.gov (United States)

    Mao, Shi-Wei; Chen, Huang; Yu, Li-Fang; Lv, Fang; Xing, Ya-Jing; Liu, Ting; Xie, Jia; Tang, Jie; Yi, Zhengfang; Yang, Fan

    2016-10-21

    A series of new seco-A ring bile acid diamides were synthesized, and their antiproliferative activities against PC3M (prostate), HT29 (colon) and ES-2 (ovarian) cancer cell lines were investigated using SRB assays. Most synthesized compounds presented improved antiproliferative activities compared to the parent bile acids (IC50 > 80 μM), especially the piperazine conjugated compound 27 with IC50 values of 1.07, 4.58 and 3.86 μM against PC3M, HT29 and ES-2 cancer cell lines, respectively. In addition, all the tested compounds showed less cytotoxic activity on a noncancerous cell line (HAF), and the most active compound 27 exhibited the highest selectivity (Selectivity Index, SI(PC3M) = 26.3). Furthermore, 27 could also enhance G1 arrest in PC3M cell, revealed by cell cycle analysis, and increase anti-migration activity on PC3M cells, confirmed by transwell migration assay. PMID:27448915

  2. Interactions between Human Liver Fatty Acid Binding Protein and Peroxisome Proliferator Activated Receptor Selective Drugs

    Directory of Open Access Journals (Sweden)

    Tony Velkov

    2013-01-01

    Full Text Available Fatty acid binding proteins (FABPs act as intracellular shuttles for fatty acids as well as lipophilic xenobiotics to the nucleus, where these ligands are released to a group of nuclear receptors called the peroxisome proliferator activated receptors (PPARs. PPAR mediated gene activation is ultimately involved in maintenance of cellular homeostasis through the transcriptional regulation of metabolic enzymes and transporters that target the activating ligand. Here we show that liver- (L- FABP displays a high binding affinity for PPAR subtype selective drugs. NMR chemical shift perturbation mapping and proteolytic protection experiments show that the binding of the PPAR subtype selective drugs produces conformational changes that stabilize the portal region of L-FABP. NMR chemical shift perturbation studies also revealed that L-FABP can form a complex with the PPAR ligand binding domain (LBD of PPARα. This protein-protein interaction may represent a mechanism for facilitating the activation of PPAR transcriptional activity via the direct channeling of ligands between the binding pocket of L-FABP and the PPARαLBD. The role of L-FABP in the delivery of ligands directly to PPARα via this channeling mechanism has important implications for regulatory pathways that mediate xenobiotic responses and host protection in tissues such as the small intestine and the liver where L-FABP is highly expressed.

  3. CHANGES IN SELECTIVITY OF GAMMA-AMINOBUTYRIC ACID FORMATION EFFECTED BY FERMENTATION CONDITIONS AND MICROORGANISMS RESOURCES

    Directory of Open Access Journals (Sweden)

    Kamila Kovalovská

    2011-10-01

    Full Text Available In this study we observe the effect of fermentation conditions and resources of microorganisms for production of γ-aminobutyric acid (GABA. The content of produced GABA depends on various conditions such as the amount of precursor, an addition of salt, enzyme and the effect of pH. The highest selectivity of GABA (74.0 % from the precursor (L-monosodium glutamate has been determinate in the follow conditions: in the presence of pre-cultured microorganisms from Encián cheese in amount 1.66 % (w/v the source of microorganisms/volume of the fermentation mixture, after the addition of 0.028 % (w/v of CaCl2/volume of the fermentation mixture, 100 μM of pyridoxal-5-phosphate (P-5-P and the GABA precursor concentration in the fermentation mixture 2.6 mg ml-1 in an atmosphere of gas nitrogen. Pure cultures of lactic acid bacteria increased the selectivity of GABA by an average of 20 % compared with bacteria from the path of Encián.

  4. Determination of tartaric acid in wines by FIA with tubular tartrate-selective electrodes.

    Science.gov (United States)

    Sales, M G; Amaral, C E; Matos, C M

    2001-03-01

    A flow injection analysis (FIA) system comprising a tartrate-(TAT) selective electrode has been developed for determination of tartaric acid in wines. Several electrodes constructed for this purpose had a PVC membrane with a complex of quaternary ammonium and TAT as anion exchanger, a phenol derivative as additive, and a more or less polar mediator solvent. Characterization of the electrodes showed behavior was best for membranes with o-nitrophenyl octyl ether as solvent. On injection of 500 microL into a phosphate buffer carrier (pH = 3.1; ionic strength 10(-2) mol/L) flowing at 3 mL/min, the slope was 58.06 +/- 0.6 with a lower limit of linear range of 5.0 x 10(-4) mol/L TAT and R2 = 0.9989. The interference of several species, e.g. chloride, bromide, iodide, nitrate, gallic acid, tannin, sucrose, glucose, fructose, acetate, and citrate, was evaluated in terms of potentiometric selectivity coefficients. The Hofmeister series was followed for inorganic species and the most interfering organic ion was citrate. When red and white wines were analyzed and the results compared with those from an independent method they were found to be accurate, with relative standard deviations below 5.0%.

  5. Effect of Selected Organic Acids on Cadmium Sorption by Variable-and Permanent-Charge Soils

    Institute of Scientific and Technical Information of China (English)

    HU Hong-Qing; LIU Hua-Liang; HE Ji-Zheng; HUANG Qiao-Yun

    2007-01-01

    Batch equilibrium experiments were conducted to investigate cadmium (Cd) sorption by two permanent-charge soils, a yellow-cinnamon soil and a yellow-brown soil, and two variable-charge soils, a red soil and a latosol, with addition of selected organic acids (acetate, tartrate, and citrate). Results showed that with an increase in acetate concentrations from 0 to 3.0 mmol L-1, Cd sorption percentage by the yellow-cinnamon soil, the yellow-brown soil, and the latosol decreased. The sorption percentage of Cd by the yellow-cinnamon soil and generally the yellow-brown soil (permanent-charge soils)decreased with an increase in tartrate concentration, but increased at low tartrate concentrations for the red soil and the latosol. Curves of percentage of Cd sorption for citrate were similar to those for tartrate. For the variable-charge soils with tartrate and citrate, there were obvious peaks in Cd sorption percentage. These peaks, where organic acids had maximum influence, changed with soil type, and were at a higher organic acid concentration for the variable-charge soils than for the permanent charge soils. Addition of cadmium after tartrate adsorption resulted in higher sorption increase for the variable-charge soils than permanent-charge soils. When tartrate and Cd solution were added together, sorption of Cd decreased with tartrate concentration for the yellow-brown soil, but increased at low tartrate concentrations and then decreased with tartrate concentration for the red soil and the latosol.

  6. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Soyeon; Shin, Soyeon; Lim, Kyu [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of); Heo, Jun Young, E-mail: junyoung3@gmail.com [Brainscience Institute, Chungnam National University, Daejeon (Korea, Republic of); Kweon, Gi Ryang, E-mail: mitochondria@cnu.ac.kr [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of)

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  7. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    International Nuclear Information System (INIS)

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis

  8. Yoghurts with addition of selected vegetables: acidity, antioxidant properties and sensory quality

    Directory of Open Access Journals (Sweden)

    Dorota Najgebauer-Lejko

    2014-03-01

    Full Text Available Background. Yoghurt is a fermented milk of unique sensory, nutritive and dietetic value offered in a variety of types and in different fl avours. Vegetables belong to the group of food products rich in antioxidant substances (e.g., vitamin C, carotenoids, tocopherols, polyphenols which regular consumption lowers the risk of many diseases including cancers and cardiovascular disorders. The aim of the present work was to manufacture and assess the acidity, sensory quality and antioxidant capacity of yoghurts with addition of selected vegetables during 2-week refrigerated storage. Material and methods. The vegetable preparations (carrot, pumpkin, broccoli and red sweet pepper were added to the cow’s milk fermented using DVS type yoghurt culture after initial cooling to 15-20°C in the amount of 10% (w/w. The following analyses were performed: determination of pH, titratable acidity, antioxidant activity by ferric reducing antioxidant power (FRAP and 2,2’-diphenyl-1-picrylhydrazyl (DPPH method as well as sensory evaluation and were conducted after 1, 7 and 14 days of cold storage. Results. The yoghurt supplementation with selected vegetables had no signifi cant effect on the pH and titratable acidity level. The highest ability to scavenge DPPH radicals was stated for yoghurts with broccoli and red sweet pepper. The latter treatment gained the highest notes in sensory evaluation. All vegetable yoghurts were characterised by higher than the natural yoghurt FRAP values measured directly after production. However, the level of this parameter signifi cantly decreased after storage. Conclusions. The red sweet pepper additive was the most benefi cial regarding antioxidant properties and organoleptic acceptance of the studied yoghurts.

  9. The Potential Benefits and Adverse Effects of Phytic Acid Supplement in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    F. O. Omoruyi

    2013-01-01

    Full Text Available In this study, the effect of phytic acid supplement on streptozotocin-induced diabetic rats was investigated. Diabetic rats were fed rodent chow with or without phytic acid supplementation for thirty days. Blood and organ samples were collected for assays. The average food intake was the highest and the body weight gain was the lowest in the group fed phytic acid supplement compared to the diabetic and normal control groups. There was a downward trend in intestinal amylase activity in the group fed phytic acid supplement compared to the other groups. The spike in random blood glucose was the lowest in the same group. We noted reduced serum triglycerides and increased total cholesterol and HDL cholesterol levels in the group fed phytic acid supplement. Serum alkaline phosphatase and alanine amino transferase activities were significantly (P<0.05 increased by phytic acid supplementation. Systemic IL-1β level was significantly (P<0.05 elevated in the diabetic control and supplement treated groups. The liver lipogenic enzyme activities were not significantly altered among the groups. These results suggest that phytic acid supplementation may be beneficial in the management of diabetes mellitus. The observed adverse effect on the liver may be due to the combined effect of streptozotocin-induced diabetes and phytic acid supplementation.

  10. The gender difference of selective serotonin reuptake inhibitor, fluoxetine in adult rats with stress-induced gastric ulcer.

    Science.gov (United States)

    Abdel-Sater, Khaled A; Abdel-Daiem, Wafaa M; Sayyed Bakheet, Mohamad

    2012-08-01

    We investigated the gender difference of selective serotonin reuptake inhibitor, fluoxetine in adult rats with stress-induced gastric ulcer. The rats were randomly divided into six groups: Group I, control males and group II, control females; group III, acute cold restraint stressed males and group IV, acute cold restraint stressed females; group V, fluoxetine-treated stressed males and group VI, fluoxetine-treated stressed females. Acute cold restraint stress was established by fixing the four limbs of the rat and placing it in a refrigerator at 4°C for 3h. Fluoxetine was given intraperitoneal in a single dose of 10mg/kg/day. After 2 weeks, stomach and brain tissues were collected for the assay of gastric malonaldehyde (MDA), catalase, nitric oxide (NO) and cortical gamma aminobutyric acid (GABA). Stressed animals exhibited increased total acidity in association with decreased gastric secretion volume. Gastric MDA was increased while gastric catalase, NO, and cortical GABA were decreased in stressed male rats when compared to stressed females. However, fluoxetine administration attenuated these stress-induced changes especially in stressed male animals. Stressed male rats were more responsive to the antiulcer effect of fluoxetine more than stressed females. However, fluoxetine might be considered to be the first-choice drug in depressive patients with gastric ulcers in the future.

  11. Comparing organic acids and salt derivatives as antimicrobials against selected poultry-borne Listeria monocytogenes strains in vitro.

    Science.gov (United States)

    Lues, Jan Frederick Rykers; Theron, Maria Magdalena

    2012-12-01

    This article reports on the antilisterial properties of selected organic acids and salt derivatives in order to suggest possible alternatives in food preservation and pathogen control in the poultry meat processing industry. The susceptibility of two Listeria monocytogenes isolates was assessed against five organic acids (lactic, acetic, malic, citric, and propionic) and two acid-salt derivatives (sorbic acid [potassium salt] and benzoic acid [sodium salt]) across a series of pH environments. Minimum inhibitory concentrations (MICs) of the acids were tested against the two strains by means of an agar-dilution method. In general, strain CC60 was found to be more resistant than strain CC77 to both organic acids and salts. At pH values of 7 and above, high MIC levels (low susceptibility) were noted for potassium sorbate, sodium benzoate, and lactic acids, whereas susceptibility at lower pH increased reaching pH5 where the isolates were susceptible to all the organic acids tested. A small increase in pH notably reduced antimicrobial activity against the organisms. At pH 7, the isolates just about lost susceptibility to benzoic, lactic, malic, and sorbic acids. Although the activity of the majority of acids was linked to pH, some acids were not as closely related (e.g., potassium sorbate, sodium benzoate, and citric acid), and this suggests that the type of organic acids plays a role in inhibition. The relatively high MICs reported for compounds that are conventionally used as preservatives against Listeria spp. raise concern. The results furthermore suggest that the type of organic acid used to set pH, and not only pH alone, plays a role in determining inhibition. It was confirmed that a "one size fits all" approach to preservation is not always effective. Furthermore, the need for microbiological data to the subspecies level to inform the selection of preservatives was highlighted. PMID:23190165

  12. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  13. Lactic acid bacteria and bifidobacteria attenuate the proinflammatory response in intestinal epithelial cells induced by Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Carey, Christine M; Kostrzynska, Magdalena

    2013-01-01

    Inflammation is a physiological response to infections and tissue injury; however, abnormal immune responses can give rise to chronic inflammation and contribute to disease progression. Various dietary components, including probiotic lactic acid bacteria and prebiotics, have the potential to modulate intestinal inflammatory responses. One factor in particular, the chemokine interleukin-8 (IL-8, CXCL-8), is one of the major mediators of the inflammatory response. The purpose of this study was to investigate modulation of the inflammatory host response induced by Salmonella enterica serovar Typhimurium DT104 in the presence of selected probiotics and lactic acid bacteria (LAB) isolated from human sources, dairy products, and farm animals. IL-8 gene expression and protein production in HT-29 cells were evaluated by real-time PCR and ELISA, respectively. Pre-incubation of HT-29 cells with Lactobacillus kefir IM002, Bifidobacterium adolescentis FRP 61, Bifidobacterium longum FRP 68 and FRP 69, Bifidobacterium breve FRP 334, and Leuconostoc mesenteroides IM080 significantly inhibited IL-8 secretion induced by Salmonella Typhimurium DT104. Co-culture of selected probiotics and Salmonella Typhimurium DT104 reduced IL-8 production, while potential probiotics and LAB had no effect on IL-8 secretion in HT-29 cells preincubated with Salmonella Typhimurium DT104 prior to adding probiotics. Lactobacillus kefir IM002 supernatant also significantly reduced IL-8 production. In conclusion, our study suggests that probiotic bifidobacteria and LAB modulate cytokine induction and possess anti-inflammatory properties; however, the effectiveness is strain dependent.

  14. Autophagy induction promotes aristolochic acid-I-induced renal injury in vivo and in vitro

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Aristolochic acid induced autophagy in vivo and in vitro. • Autophagy induced by aristolochic acid could promote cell apoptosis. • Inhibition autophagy by silencing ATG5 could prevent cell from programmed cell death induced by aristolochic acid. - Abstract: Studies have found that ingestion of aristolochic acid (AA) causes nephropathy first by inducing renal tubular cell apoptosis acutely. It is currently unknown whether crosstalk between autophagy and apoptosis orchestrates the fate of tubular cells in acute AA nephropathy. We tested this hypothesis by acute administration of AA in vivo and in vitro. Autophagy was first induced in vivo through enhancing Atg5 and LC3-II expressions in kidneys of AA-I-treated rats. Punctuate LC3-GFP dots and autophagosomes were detected in this acute AA-I nephropathy rat model. We subsequently utilized normal rat renal proximal tubular epithelial cells (NRK52E) to study the autophagy mechanisms involved in acute AA-I nephropathy, with 100 μM AA-I (median lethal dose 50) given in vitro. Cleavage of poly (ADP-ribose) polymerase (PARP), nuclear condensation, and fragmentation were demonstrated in the AA-I-treated NRK52E cells. Furthermore, AA-I induced Atg5 and LC3-II expressions and punctuated LC3-GFP dots. Autophagy flux by using lysosome inhibitor E64 induced the accumulation of LC3-II, which further promoted apoptosis through enhancing PARP cleavage. Inhibition of autophagy by 3-methyl adenine also led to the attenuation of AA-I-induced apoptosis, manifesting as decreased PARP cleavage, nuclei condensation, and decreased the number of cells negative for acridine orange/ethidium bromide staining. In addition, knockdown of Atg5 by short hairpin RNA attenuated LC3-II expression and PARP cleavage in NRK52E cells. Taken together, these findings suggested that the acute phase of AA-I-induced nephropathy is associated with induction of Atg5-dependent autophagy, which promotes renal tubular cell

  15. Extreme hypoxic conditions induce selective molecular responses and metabolic reset in detached apple fruit

    Directory of Open Access Journals (Sweden)

    Dubravka eCukrov

    2016-02-01

    Full Text Available The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control and hypoxic (0.4 and 0.8 kPa oxygen conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1,000 genes differentially expressed when comparing 0.4 vs 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These

  16. 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)

  17. Fatty acid and sterol contents during tulip leaf senescence induced by methyl jasmonate

    Directory of Open Access Journals (Sweden)

    Marian Saniewski

    2013-12-01

    Full Text Available It has been shown previously that methyl jasmonate (JA-Me applied in lanolin paste on the bottom surface of intact tulip leaves causes a rapid and intense its senescence. The aim of this work was to study the effect of JA-Me on free and bound fatty acid and sterol contents during tulip leaf senescence. The main free and bound fatty acids of tulip leaf, in decreasing order of their abundance, were linolenic, linoleic, palmitic, oleic, stearic and myristic acids. Only the content of free linolenic acid decreased after treatment with JA-Me during visible stage of senescence. ß-Sitosterol (highest concentration, campesterol, stigmasterol and cholesterol were identified in tulip leaf. Methyl jasmonate evidently increased the level of ß-sitosterol, campesterol and stigmasterol during induced senescence. It is suggested that the increase in sterol concentrations under the influence of methyl jasmonate induced changes in membrane fluidity and permeability, which may be responsible for senescence.

  18. Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Liese, Juliane; Abhari, Behnaz Ahangarian; Fulda, Simone

    2015-08-28

    Chemotherapy resistance of hepatocellular carcinoma (HCC) is still a major unsolved problem highlighting the need to develop novel therapeutic strategies. Here, we identify a novel synergistic induction of cell death by the combination of the Smac mimetic BV6, which antagonizes Inhibitor of apoptosis (IAP) proteins, and the triterpenoid oleanolic acid (OA) in human HCC cells. Importantly, BV6 and OA also cooperate to suppress long-term clonogenic survival as well as tumor growth in a preclinical in vivo model of HCC underscoring the clinical relevance of our findings. In contrast, BV6/OA cotreatment does not exert cytotoxic effects against normal primary hepatocytes, pointing to some tumor selectivity. Mechanistic studies show that BV6/OA cotreatment leads to DNA fragmentation and caspase-3 cleavage, while supply of the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) revealed a cell type-dependent requirement of caspases for BV6/OA-induced cell death. The receptor interacting protein (RIP)1 kinase Inhibitor Necrostatin-1 (Nec-1) or genetic knockdown of RIP1 fails to rescue BV6/OA-mediated cell death, indicating that BV6/OA cotreatment does not primarily engage necroptotic cell death. Notably, the addition of several reactive oxygen species (ROS) scavengers significantly decreases BV6/OA-triggered cell death, indicating that ROS production contributes to BV6/OA-induced cell death. In conclusion, cotreatment of Smac mimetic and OA represents a novel approach for the induction of cell death in HCC and implicates further studies.

  19. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

  20. Hypochlorite-induced oxidation of amino acids, peptides and proteins

    DEFF Research Database (Denmark)

    Hawkins, C L; Pattison, D I; Davies, Michael Jonathan

    2003-01-01

    Activated phagocytes generate the potent oxidant hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is known to react with a number of biological targets including proteins, DNA, lipids and cholesterol. Proteins are likely to be major targets for reaction...... with HOCl within a cell due to their abundance and high reactivity with HOCl. This review summarizes information on the rate of reaction of HOCl with proteins, the nature of the intermediates formed, the mechanisms involved in protein oxidation and the products of these reactions. The predicted targets...... for reaction with HOCl from kinetic modeling studies and the consequences of HOCl-induced protein oxidation are also discussed....

  1. Theoretical study of ultraviolet induced photodissociation dynamics of sulfuric acid

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Tatsuhiro; Ohta, Ayumi; Suzuki, Tomoya; Ikeda, Kumiko [Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-Cho, Chiyoda-ku, Tokyo 102-8554 (Japan); Danielache, Sebastian O. [Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-Cho, Chiyoda-ku, Tokyo 102-8554 (Japan); Earth-Life Science Institute (ELSI), Tokyo Institute of Technology (Japan); Department of Environmental Science and Techonology, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yoohama 226-8502 (Japan); Nanbu, Shinkoh, E-mail: shinkoh.nanbu@sophia.ac.jp [Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-Cho, Chiyoda-ku, Tokyo 102-8554 (Japan)

    2015-05-01

    Highlights: • Photodissociation dynamics of H{sub 2}SO{sub 4} at low-lying electronically excited states were investigated. • Photochemical processes were simulated by on-the-fly ab initio MD. • Sulfuric acid after the excitation to the S{sub 1} state dissociated to HSO{sub 4}(1{sup 2}A″) + H({sup 2}S). • Sulfuric acid after the excitation to the S{sub 2} state dissociated to HSO{sub 4}(2{sup 2}A″) + H({sup 2}S). • The energy region of the UV spectra where NMD fractionation may occur is predicted. - Abstract: Photodissociation dynamics of sulfuric acid after excitation to the first and second excited states (S{sub 1} and S{sub 2}) were studied by an on-the-fly ab initio molecular dynamics simulations based on the Zhu–Nakamura version of the trajectory surface hopping (ZN-TSH). Forces acting on the nuclear motion were computed on-the-fly by CASSCF method with Dunning’s augmented cc-pVDZ basis set. It was newly found that the parent molecule dissociated into two reaction-channels (i) HSO{sub 4}(1{sup 2}A″) + H({sup 2}S) by S{sub 1}-excitation, and (ii) HSO{sub 4}(2{sup 2}A″) + H({sup 2}S) by S{sub 2}-excitation. The direct dissociation dynamics yield products different from the SO{sub 2} + 2OH fragments often presented in the literature. Both channels result in the same product and differs only in the electronic state of the HSO{sub 4} fragment{sub .} The trajectories running on S{sub 2} do not hop with S{sub 0} and a nonadiabatic transition happens at the S{sub 2}–S{sub 1} conical intersection located at a longer OH bond-length than the S{sub 1}–S{sub 0} intersection producing an electronic excited state (2{sup 2}A″) of HSO{sub 4} product.

  2. Verification of a characterization method of the laser-induced selective activation based on industrial lasers

    DEFF Research Database (Denmark)

    Zhang, Yang; Hansen, Hans Nørgaard; Tang, Peter T.;

    2013-01-01

    In this article, laser-induced selective activation (LISA) for subsequent autocatalytic copper plating is performed by several types of industrial scale lasers, including a Nd:YAG laser, a UV laser, a fiber laser, a green laser, and a short pulsed laser. Based on analysis of all the laser-machine...

  3. Moulded interconnect device fabrication by two shot molding and lasert induced selective activation

    DEFF Research Database (Denmark)

    Sun, Jie; Hansen, Hans Nørgaard

    interconnect device was achieved with two innovative processes such as two shot injection molding which combines platetable and none-platetable thermoplastics, and laser induced selective activation which uses a laser to draw circuit on the thermoplastic surface containing laser sensitive additive. Different...

  4. Selective population of high-j orbitals in Er nuclei by heavy-ion--induced transfer

    International Nuclear Information System (INIS)

    Selective population of high-j and high-K states in /sup 167,169,171/Er nuclei has been observed in heavy-ion--induced single-neutron-transfer reactions. Gamma rays in coincidence with outgoing particles have been used to aid in level assignments and several previously unobserved high-j states have been identified

  5. Site-selective nanoscale-polymerization of pyrrole on gold nanoparticles via plasmon induced charge separation.

    Science.gov (United States)

    Takahashi, Y; Furukawa, Y; Ishida, T; Yamada, S

    2016-04-28

    We proposed a nanoscale oxidative polymerization method which enables site-selective deposition on the surface of gold nanoparticles (AuNPs) combined with TiO2 by using plasmon induced charge separation (PICS) under visible-to-near infrared (IR) light irradiation. The method also revealed that the anodic site of PICS was located at the surface of AuNPs.

  6. STRUCTURAL REMODELING OF PROTEOGLYCANS UPON RETINOIC ACID-INDUCED DIFFERENTIATION OF NCCIT CELLS*

    OpenAIRE

    Gasimli, Leyla; Stansfield, Hope E.; Nairn, Alison V.; Liu, Haiying; Janet L. Paluh; Yang, Bo; Dordick, Jonathan S.; Moremen, Kelley W.; Linhardt, Robert J.

    2012-01-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increa...

  7. Bile Acid-Induced Arrhythmia Is Mediated by Muscarinic M2 Receptors in Neonatal Rat Cardiomyocytes

    OpenAIRE

    Sheikh Abdul Kadir, Siti H; Michele Miragoli; Shadi Abu-Hayyeh; Moshkov, Alexey V.; Qilian Xie; Verena Keitel; Viacheslav O. Nikolaev; Catherine Williamson; Julia Gorelik

    2010-01-01

    BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC), which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM). Apart from their hepatic functions bile acids are ubiquitous signallin...

  8. Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.

    OpenAIRE

    Handa, S I; FREESTONE, S.

    1990-01-01

    We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.

  9. Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II

    OpenAIRE

    Koenitzer, Jeffrey R; Gustavo Bonacci; Woodcock, Steven R.; Chen-Shan Chen; Nadiezhda Cantu-Medellin; Kelley, Eric E.; Schopfer, Francisco J.

    2016-01-01

    Nitro-fatty acids (NO2-FA) are metabolic and inflammatory-derived electrophiles that mediate pleiotropic signaling actions. It was hypothesized that NO2-FA would impact mitochondrial redox reactions to induce tissue-protective metabolic shifts in cells. Nitro-oleic acid (OA-NO2) reversibly inhibited complex II-linked respiration in isolated rat heart mitochondria in a pH-dependent manner and suppressed superoxide formation. Nitroalkylation of Fp subunit was determined by BME capture and the s...

  10. Radiation-induced destruction peculiarities of hydroxyl containing amino acids in diluted aqueous solution

    International Nuclear Information System (INIS)

    Amino acids aqueous solution of alpha-alanine and beta-alanine, serine, threonine (concentration 5*10-4 M) were irradiated with dose rate 0.35 Gy/s in range 100-1100 Gy and analysed. Effectiveness of radiation-induced decomposition process depends on row of factors: concentration of amino acid aqueous solution, pH, oxygen presence and other acceptors

  11. Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids

    OpenAIRE

    Pujos-Guillot, Estelle; Pickering, Gisèle; Lyan, Bernard; Ducheix, Gilles; Brandolini-Bunlon, Marion; Glomot, Françoise; Dardevet, Dominique; Dubray, Claude; PAPET, Isabelle

    2011-01-01

    Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on ...

  12. Comparative Study of Domoic Acid and Okadaic Acid Induced - Chromosomal Abnormalities in the CACO-2 Cell Line

    Directory of Open Access Journals (Sweden)

    Edmond E. Creppy

    2006-03-01

    Full Text Available Okadaic Acid (OA the major diarrheic shellfish poisoning (DSP toxin is known as a tumor promoter and seems likely implicated in the genesis of digestive cancer. Little is known regarding genotoxicity and carcinogenicity of Domoic Acid (DA, the major Amnesic Shellfish Poisoning (ASP toxin. Both OA and DA occur in seafood and are of human health concerns. Micronuclei (MN arise from abnormalities in nuclear division during mitosis due to a failure of the mitotic spindle or by complex chromosomal configurations that pose problems during anaphase. In order to evaluate the ability of okadaic acid (OA and domoic acid (DA to induce DNA damage we performed the micronucleus assay using the Caco-2 cell line. To discriminate between a clastogenic or aneugenic effect of OA and DA, the micronucleus assay was conducted by cytokinesis-block micronucleus assay using cytochalasin B with Giemsa staining and/or acridine orange staining, in parallel to fluorescence in situ hybridization (FISH using a concentrated human pan-centromeric chromosome paint probe. Our results showed that OA and DA significantly increased the frequency of MN in Caco-2 cells. The MN caused by OA are found in mononucleated cells and binucleated cells, whereas those caused by DA are mainly in binucleated cells. The results of FISH analysis showed that OA induced centromere-positive micronuclei and DA increased the percentage of MN without a centromeric signal. In conclusion, both OA and DA bear mutagenic potential as revealed in Caco-2 cells by induction of MN formation. Moreover, OA induced whole chromosome loss suggesting a specific aneugenic potential, whereas DA seems simply clastogenic. At present, one cannot rule out possible DNA damage of intestinal cells if concentrations studied are reached in vivo, since this may happen with concentrations of toxins just below regulatory limits in case of frequent consumption of contaminated shell fishes.

  13. Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes.

    Science.gov (United States)

    Wu, I; Shin, S C; Cao, Y; Bender, I K; Jafari, N; Feng, G; Lin, S; Cidlowski, J A; Schleimer, R P; Lu, N Z

    2013-01-01

    Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expressing the GR-A, -B, or -C, but not the GR-D, isoform. cDNA microarray analyses of cells sensitive (GR-C3) and insensitive (GR-D3) to DEX revealed glucocorticoid-induced proapoptotic transcriptomes. Genes that were regulated by the proapoptotic GR-C3, but not by the GR-D3, isoform likely contributed to glucocorticoid-induced apoptosis. The identified genes include those that are directly involved in apoptosis and those that facilitate cell killing. Chromatin immunoprecipitation assays demonstrated that distinct chromatin modification abilities may underlie the distinct functions of GR isoforms. Interestingly, all GR isoforms, including the GR-D3 isoform, suppressed mitogen-stimulated cytokines. Furthermore, the GR-C isoforms were selectively upregulated in mitogen-activated primary T cells and DEX treatment induced GR-C target genes in activated T cells. Cell-specific expressions and functions of GR isoforms may help to explain the tissue- and individual-selective actions of glucocorticoids and may provide a basis for developing improved glucocorticoids. PMID:23303127

  14. Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor ß ligands

    DEFF Research Database (Denmark)

    Lund, Birgitte W.; Knapp, Anne Eeg; Piu, Fabrice;

    2009-01-01

    We recently discovered the isoform selective RAR beta 2 ligand 4'-octyl-4-biphenylcarboxylic acid (3, AC-55649). Although 3 is highly potent at RAR beta 2 and displays excellent selectivity, solubility issues make it unsuitable for drug development. Herein we describe the exploration of the SAR in...

  15. Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

    Science.gov (United States)

    Whiteman, Matthew; Hooper, D. Craig; Scott, Gwen S.; Koprowski, Hilary; Halliwell, Barry

    2002-09-01

    Chronic inflammation results in increased nitrogen monoxide (NO) formation and the accumulation of nitrite (NO). Neutrophils stimulated by various inflammatory mediators release myeloperoxidase to produce the cytotoxic agent hypochlorous acid (HOCl). Exposure of chondrocytic SW1353 cells to HOCl resulted in a concentration- and time-dependent loss in viability, ATP, and glutathione levels. Treatment of cells with NO but not nitrate (NO) substantially decreased HOCl-dependent cellular toxicity even when NO was added at low (μM) concentrations. In contrast, NO alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO accumulation at chronic inflammatory sites, where both HOCl and NO are overproduced, may be cytoprotective against damage caused by HOCl. We propose that this is because HOCl is removed by reacting with NO to give nitryl chloride (NO2Cl), which is less damaging in our cell system. inflammation | cell toxicity | nitryl chloride | nitric oxide | arthritis

  16. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    Science.gov (United States)

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  17. Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice.

    Science.gov (United States)

    Choi, You-Jin; Lee, Chae-Hyeon; Lee, Kang-Yo; Jung, Seung-Hwan; Lee, Byung-Hoon

    2015-06-01

    Tetracycline induces microvesicular steatosis, which has a poor long-term prognosis and a higher risk of steatohepatitis development compared with macrovesicular steatosis. Recent gene expression studies indicated that tetracycline treatment affects the expression of many genes associated with fatty acid transport and esterification. In this study, we investigated the role of fatty acid transport and esterification in tetracycline-induced steatosis. Intracellular lipid accumulation and the protein expression of fatty acid translocase (FAT or CD36) and diacylglycerol acyltransferase (DGAT) 2 were increased in both mouse liver and HepG2 cells treated with tetracycline at 50 mg/kg (intraperitoneal injection, i.p.) and 100 μM, respectively. Tetracycline increased the cellular uptake of boron-dipyrromethene-labeled C16 fatty acid, which was abolished by CD36 RNA interference. Oleate-induced cellular lipid accumulation was further enhanced by co-incubation with tetracycline. Tetracycline downregulated extracellular signal-regulated kinase (ERK) phosphorylation, which negatively regulated DGAT2 expression. U0126, a specific ERK inhibitor, also increased DGAT2 expression and cellular lipid accumulation. DGAT1 and 2 knock-down with specific small interfering (si)-RNA completely abrogated the steatogenic effect of tetracycline in HepG2 cells. Taken together, our data showed that tetracycline induces lipid accumulation by facilitating fatty acid transport and triglyceride esterification by upregulating CD36 and DGAT2, respectively. PMID:25745068

  18. Hepatocyte transplantation in bile salt export pump-deficient mice: selective growth advantage of donor hepatocytes under bile acid stress

    OpenAIRE

    Chen, Huey-Ling; Chen, Hui-Ling; Yuan, Ray-Hwang; Wu, Shang-Hsin; Chen, Ya-Hui; Chien, Chin-Sung; Chou, Shi-Ping; Wang, Renxue; Ling, Victor; Chang, Mei-Hwei

    2012-01-01

    The bile salt export pump (Bsep) mediates the hepatic excretion of bile acids, and its deficiency causes progressive familial intrahepatic cholestasis. The current study aimed to induce bile acid stress in Bsep −/− mice and to test the efficacy of hepatocyte transplantation in this disease model. We fed Bsep −/− and wild-type mice cholic acid (CA) or ursodeoxycholic acid (UDCA). Both CA and UDCA caused cholestasis and apoptosis in the Bsep −/− mouse liver. Wild-type mice had minimal liver inj...

  19. Enhancement of taxol-induced apoptosis by inhibition of NF-κB with ursorlic acid

    Science.gov (United States)

    Li, Yunlong; Xing, Da

    2007-05-01

    Taxol is known to inhibit cell growth and triggers significant apoptosis in various cancer cells, and activation of proliferation factor NF-κB during Taxol-induced apoptosis is regarded as a main reason resulting in tumor cells resistance to Taxol. It has been found that ursorlic acid can inhibit the activation of NF-κB. In order to study whether ursorlic acid can enhance the Taxol-induced apoptosis, we use fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to compare the difference of caspase-3 activation between Taxol alone and Taxol combined ursorlic acid. With laser scanning confocal microscopy, we find that ursorlic acid, a nontoxic food component, sensitizes ASTC-a-1 cells more efficiently to Taxol-induced apoptosis by advanced activation of caspase 3. The result also suggests that there would be a synergistic effect between Taxol and ursorlic acid, and the more detailed mechanism of synergistic effect needs to be clarified further, such as the correlations among NF-κB, Akt, caspase 8, which leads to the advanced activation of caspase 3 during combined treatment of Taxol and ursorlic acid. Moreover, this may be a new way to improve Taxol-dependent tumor therapy.

  20. Protective effects of gallic acid against spinal cord injury-induced oxidative stress.

    Science.gov (United States)

    Yang, Yong Hong; Wang, Zao; Zheng, Jie; Wang, Ran

    2015-08-01

    The present study aimed to investigate the role of gallic acid in oxidative stress induced during spinal cord injury (SCI). In order to measure oxidative stress, the levels of lipid peroxide, protein carbonyl, reactive oxygen species and nitrates/nitrites were determined. In addition, the antioxidant status during SCI injury and the protective role of gallic acid were investigated by determining glutathione levels as well as the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. Adenosine triphophatase (ATPase) enzyme activities were determined to evaluate the role of gallic acid in SCI-induced deregulation of the activity of enzymes involved in ion homeostasis. The levels of inflammatory markers such as nuclear factor (NF)-κB and cycloxygenase (COX)-2 were determined by western blot analysis. Treatment with gallic acid was observed to significantly mitigate SCI-induced oxidative stress and the inflammatory response by reducing the oxidative stress, decreasing the expression of NF-κB and COX-2 as well as increasing the antioxidant status of cells. In addition, gallic acid modulated the activity of ATPase enzymes. Thus the present study indicated that gallic acid may have a role as a potent antioxidant and anti-inflammatory agent against SCI. PMID:25955644

  1. 37% Phosphoric Acid Induced Stronger Matrix Metalloproteinase-8 Expression of the Dental Pulp than 19% Ethylene Diamine Tetraacetic Acid

    Directory of Open Access Journals (Sweden)

    Nadie Fatimatuzzahro

    2014-11-01

    Full Text Available Etching agents such as ethylene diamine tetraacetic acid (EDTA and phosphoric acid which are widely used in adhesive restoration system aimed to increase for retention of restorative materials, may act a chemical irritant that induce inflammation of dental pulp. Inflammation is a body response against irritant and infectious agents. Matrix metalloproteinase-8, the major collagenolytic enzyme, degrades collagen type 1. This enzyme is expressed in low level in normal condition, however, the expression will increase during inflammation. The purpose of the present research was to study the effect of 19% EDTA and 37% phosphoric acid application as an etching agents on the MMP-8 expression of dental pulp. Forty-five male Sprague Dawley rats were divided into 3 groups. Cavity preparation was made on the occlusal surface of maxillary first molar using a round diamond bur. 19% EDTA, 37% phosphoric acid, and distilled water were applied on the surface of the cavity of the teeth in group I, II, and III subsequently. The cavity then filed by glass ionomer cements. The rats were sacrified at 1, 3, 5, 7, and 14 days after the treatment (n=3 for each day. The specimens were then processed histologically. Immunohistochemical (IHC analysis was performed using rabbit anti rat MMP-8 polyclonal antibody to examine MMP-8 expression and HE (Hematoxylen Eosin staining to observe the number of macrophages. The results showed 37% phosphoric acid application induced stronger expression of MMP-8 and higher number of macrophages than 19% EDTA. The strongest expression of MMP-8 seems on 5 days after the treatment where the highest number of macrophages were also found.

  2. How to Distinguish Conformational Selection and Induced Fit Based on Chemical Relaxation Rates

    Science.gov (United States)

    2016-01-01

    Protein binding often involves conformational changes. Important questions are whether a conformational change occurs prior to a binding event (‘conformational selection’) or after a binding event (‘induced fit’), and how conformational transition rates can be obtained from experiments. In this article, we present general results for the chemical relaxation rates of conformational-selection and induced-fit binding processes that hold for all concentrations of proteins and ligands and, thus, go beyond the standard pseudo-first-order approximation of large ligand concentration. These results allow to distinguish conformational-selection from induced-fit processes—also in cases in which such a distinction is not possible under pseudo-first-order conditions—and to extract conformational transition rates of proteins from chemical relaxation data. PMID:27636092

  3. Current approach to male infertility treatment: sperm selection procedure based on hyaluronic acid binding ability

    Directory of Open Access Journals (Sweden)

    A. V. Zobova

    2015-01-01

    Full Text Available Intracytoplasmic sperm injection into an oocyte is widely used throughout the world in assisted reproductive technologies programs in the presence of male infertility factor. However, this approach can allow selection of a single sperm, which is carrying different types of pathologies. Minimizing of any potential risks, entailing the occurrence of abnormalities in the embryos development (apoptosis, fragmentation of embryos, alterations in gene expression, aneuploidies is a very important condition for reducing the potential negative consequences resulting the manipulation with gametes. Processes that could be influenced by the embryologist must be fulfilled in safe and physiological way as much as it is possible. Data of numerous publications reporting about the positive effects of using the technology of sperm selection by hyaluronic acid binding, let make a conclusion about the high prospects of this approach in the treatment of male infertility by methods of in vitro fertilization. The selection of sperm with improved characteristics, which determine the maturity and genetic integrity, provides an opportunity to improve the parameters of pre-implantation embryogenesis, having thus a positive effect on clinical outcomes of assisted reproductive technologies programs.

  4. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  5. Light induced conversion of nitrogen dioxide into nitrous acid on submicron humic acid aerosol

    Directory of Open Access Journals (Sweden)

    K. Stemmler

    2007-03-01

    Full Text Available The interactions of aerosols consisting of humic acids with gaseous nitrogen dioxide (NO2 were investigated under different light conditions in aerosol flow tube experiments at ambient pressure and temperature. The results show that NO2 is converted on the humic acid aerosol into nitrous acid (HONO, which is released from the aerosol and can be detected in the gas phase at the reactor exit. The formation of HONO on the humic acid aerosol is strongly activated by light: In the dark, the HONO-formation was below the detection limit, but it was increasing with the intensity of the irradiation with visible light. Under simulated atmospheric conditions with respect to the actinic flux, relative humidity and NO2-concentration, reactive uptake coefficients γrxn for the NO2→HONO conversion on the aerosol between γrxn <10−7 (in the dark and γrxn = 6×10−6 were observed. The observed uptake coefficients decreased with increasing NO2-concentration in the range from 2.7 to 280 ppb and were dependent on the relative humidity (RH with slightly reduced values at low humidity (<20% RH and high humidity (>60% RH. The measured uptake coefficients for the NO2→HONO conversion are too low to explain the HONO-formation rates observed near the ground in rural and urban environments by the conversion of NO2→HONO on organic aerosol surfaces, even if one would assume that all aerosols consist of humic acid only. It is concluded that humic materials present on the Earth surface will have a much larger impact on the HONO-formation in the lowermost layer of the troposphere than humic materials potentially occurring in airborne particles.

  6. Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Gao Hong-Ying

    2012-05-01

    Full Text Available Abstract The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, hexadecenoic acid (HA, laminin (LN, hydroxyproline (Hyp, and glutathione (GSH, malondialdehyde (MDA, superoxide dismutase (SOD in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E staining and Masson Trichrome (MT examination. The expression of transforming growth factor-β1 (TGF-β1 and α-smooth muscle actin (α-SMA was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis.

  7. Healing Acceleration of Acetic Acid-induced Colitis by Marigold (Calendula officinalis) in Male Rats

    OpenAIRE

    Nader Tanideh; Akram Jamshidzadeh; Masood Sepehrimanesh; Masood Hosseinzadeh; Omid Koohi-Hosseinabadi; Asma Najibi; Mozhdeh Raam; Sajad Daneshi; Seyedeh-Leili Asadi-Yousefabad

    2016-01-01

    Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and o...

  8. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

    OpenAIRE

    Catoire, Milène; Alex, Sheril; Paraskevopulos, Nicolas; Mattijssen, Frits; Evers-van Gogh, Inkie; Schaart, Gert; Jeppesen, Jacob; Kneppers, Anita; Mensink, Marco; Voshol, Peter J.; Olivecrona, Gunilla; Tan, Nguan Soon; Hesselink, Matthijs K. C.; Berbée, Jimmy F.; Rensen, Patrick C N

    2014-01-01

    Physical exercise causes profound changes in energy metabolism in humans. In this study we show that resting skeletal muscle has a crucial role in the metabolic response to acute exercise. During endurance exercise, selective induction of the protein angiopoietin-like 4 (ANGPTL4) in nonexercising muscle reduces local fatty acid uptake, presumably to prevent fat overload, while directing fatty acids to the active skeletal muscle as fuel. Our data thus suggest that nonexercising muscle has a ke...

  9. Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Shen Junhui

    2012-07-01

    Full Text Available Abstract Background Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3 and eicosapentaenoic acid (EPA, 20:5 ω-3. The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood. Methods RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF secretion were evaluated. Results Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA and α-linolenic acid (ALA, while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed

  10. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    OpenAIRE

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to a...

  11. Immune escape mutants of Highly Pathogenic Avian Influenza H5N1 selected using polyclonal sera: identification of key amino acids in the HA protein.

    Directory of Open Access Journals (Sweden)

    Ioannis Sitaras

    Full Text Available Evolution of Avian Influenza (AI viruses--especially of the Highly Pathogenic Avian Influenza (HPAI H5N1 subtype--is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1, using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.

  12. Toxicity induced by Basic Violet 14, Direct Red 28 and Acid Red 26 in zebrafish larvae.

    Science.gov (United States)

    Shen, Bing; Liu, Hong-Cui; Ou, Wen-Bin; Eilers, Grant; Zhou, Sheng-Mei; Meng, Fan-Guo; Li, Chun-Qi; Li, Yong-Quan

    2015-12-01

    Basic Violet 14, Direct Red 28 and Acid Red 26 are classified as carcinogenic dyes in the European textile ecology standard, despite insufficient toxicity data. In this study, the toxicity of these dyes was assessed in a zebrafish model, and the underlying toxic mechanisms were investigated. Basic Violet 14 and Direct Red 28 showed acute toxicity with a LC50 value at 60.63 and 476.84 µg ml(-1) , respectively, whereas the LC50 of Acid Red 26 was between 2500 and 2800 µg ml(-1) . Treatment with Basic Violet 14, Direct Red 28 and Acid Red 26 resulted in common developmental abnormalities including delayed yolk sac absorption and swimming bladder deflation. Hepatotoxicity was observed in zebrafish treated with Basic Violet 14, and cardiovascular toxicity was found in zebrafish treated with Acid Red 26 at concentrations higher than 2500 µg ml(-1) . Basic Violet 14 also caused significant up-regulation of GCLC gene expression in a dose-dependent manner whereas Acid Red 26 induced significant up-regulation of NKX2.5 and down-regulation of GATA4 at a high concentration in a dose-dependent manner. These results suggest that Basic Violet 14, Direct Red 28 and Acid Red 26 induce developmental and organ-specific toxicity, and oxidative stress may play a role in the hepatotoxicity of Basic Violet 14, the suppressed GATA4 expression may have a relation to the cardiovascular toxicity of Acid Red 26.

  13. Exacerbation of alcohol-induced oxidative stress in rats by polyunsaturated fatty acids and iron load

    Directory of Open Access Journals (Sweden)

    S N Patere

    2011-01-01

    Full Text Available The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography, polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron.

  14. Prey-induced changes in the accumulation of amino acids and phenolic metabolites in the leaves of Drosera capensis L.

    Science.gov (United States)

    Kováčik, Jozef; Klejdus, Bořivoj; Stork, František; Hedbavny, Josef

    2012-04-01

    Effect of prey feeding (ants Formica fusca) on the quantitative changes in the accumulation of free amino acids, soluble proteins, phenolic metabolites and mineral nutrients in the leaves of carnivorous plant Drosera capensis was studied. Arginine was the most abundant compound in Drosera leaves, while proline was abundant in ants. The amount of the majority of amino acids and their sum were elevated in the fed leaves after 3 and 21 days, and the same, but with further enhancement after 21 days, was observed in ants. Accumulation of amino acids also increased in young non-fed leaves of fed plants. Soluble proteins decreased in ants, but were not enhanced in fed leaves. This confirms the effectiveness of sundew's enzymatic machinery in digestion of prey and suggests that amino acids are not in situ deposited, but rather are allocated within the plant. The content of total soluble phenols, flavonoids and two selected flavonols (quercetin and kaempferol) was not affected by feeding in Drosera leaves, indicating that their high basal level was sufficient for the plant's metabolism and prey-induced changes were mainly N based. The prey also showed to be an important source of other nutrients besides N, and a stimulation of root uptake of some mineral nutrients is assumed (Mg, Cu, Zn). Accumulation of Ca and Na was not affected by feeding. PMID:21140278

  15. Prey-induced changes in the accumulation of amino acids and phenolic metabolites in the leaves of Drosera capensis L.

    Science.gov (United States)

    Kováčik, Jozef; Klejdus, Bořivoj; Stork, František; Hedbavny, Josef

    2012-04-01

    Effect of prey feeding (ants Formica fusca) on the quantitative changes in the accumulation of free amino acids, soluble proteins, phenolic metabolites and mineral nutrients in the leaves of carnivorous plant Drosera capensis was studied. Arginine was the most abundant compound in Drosera leaves, while proline was abundant in ants. The amount of the majority of amino acids and their sum were elevated in the fed leaves after 3 and 21 days, and the same, but with further enhancement after 21 days, was observed in ants. Accumulation of amino acids also increased in young non-fed leaves of fed plants. Soluble proteins decreased in ants, but were not enhanced in fed leaves. This confirms the effectiveness of sundew's enzymatic machinery in digestion of prey and suggests that amino acids are not in situ deposited, but rather are allocated within the plant. The content of total soluble phenols, flavonoids and two selected flavonols (quercetin and kaempferol) was not affected by feeding in Drosera leaves, indicating that their high basal level was sufficient for the plant's metabolism and prey-induced changes were mainly N based. The prey also showed to be an important source of other nutrients besides N, and a stimulation of root uptake of some mineral nutrients is assumed (Mg, Cu, Zn). Accumulation of Ca and Na was not affected by feeding.

  16. Hepatic Fasting-Induced PPARα Activity Does Not Depend on Essential Fatty Acids.

    Science.gov (United States)

    Polizzi, Arnaud; Fouché, Edwin; Ducheix, Simon; Lasserre, Frédéric; Marmugi, Alice P; Mselli-Lakhal, Laila; Loiseau, Nicolas; Wahli, Walter; Guillou, Hervé; Montagner, Alexandra

    2016-01-01

    The liver plays a central role in the regulation of fatty acid metabolism, which is highly sensitive to transcriptional responses to nutrients and hormones. Transcription factors involved in this process include nuclear hormone receptors. One such receptor, PPARα, which is highly expressed in the liver and activated by a variety of fatty acids, is a critical regulator of hepatic fatty acid catabolism during fasting. The present study compared the influence of dietary fatty acids and fasting on hepatic PPARα-dependent responses. Pparα(-/-) male mice and their wild-type controls were fed diets containing different fatty acids for 10 weeks prior to being subjected to fasting or normal feeding. In line with the role of PPARα in sensing dietary fatty acids, changes in chronic dietary fat consumption influenced liver damage during fasting. The changes were particularly marked in mice fed diets lacking essential fatty acids. However, fasting, rather than specific dietary fatty acids, induced acute PPARα activity in the liver. Taken together, the data imply that the potent signalling involved in triggering PPARα activity during fasting does not rely on essential fatty acid-derived ligand. PMID:27669233

  17. Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens.

    Science.gov (United States)

    Nowak, Adriana; Śliżewska, Katarzyna; Otlewska, Anna

    2015-12-01

    Dietary components such as lactic acid bacteria (LAB) and prebiotics can modulate the intestinal microbiota and are thought to be involved in the reduction of colorectal cancer risk. The presented study measured, using the comet assay, the antigenotoxic activity of both probiotic and non-probiotic LAB, as well as some prebiotics and the end-products of their fermentation, against fecal water (FW). The production of short chain fatty acids by the bacteria was quantified using HPLC. Seven out of the ten tested viable strains significantly decreased DNA damage induced by FW. The most effective of them were Lactobacillus mucosae 0988 and Bifidobacterium animalis ssp. lactis Bb-12, leading to a 76% and 80% decrease in genotoxicity, respectively. The end-products of fermentation of seven prebiotics by Lactobacillus casei DN 114-001 exhibited the strongest antigenotoxic activity against FW, with fermented inulin reducing genotoxicity by 75%. Among the tested bacteria, this strain produced the highest amounts of butyrate in the process of prebiotic fermentation, and especially from resistant dextrin (4.09 μM/mL). Fermented resistant dextrin improved DNA repair by 78% in cells pre-treated with 6.8 μM methylnitronitrosoguanidine (MNNG). Fermented inulin induced stronger DNA repair in cells pre-treated with mutagens (FW, 25 μM hydrogen peroxide, or MNNG) than non-fermented inulin, and the efficiency of DNA repair after 120 min of incubation decreased by 71%, 50% and 70%, respectively. The different degrees of genotoxicity inhibition observed for the various combinations of bacteria and prebiotics suggest that this effect may be attributable to carbohydrate type, SCFA yield, and the ratio of the end-products of prebiotic fermentation. PMID:26404012

  18. Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens.

    Science.gov (United States)

    Nowak, Adriana; Śliżewska, Katarzyna; Otlewska, Anna

    2015-12-01

    Dietary components such as lactic acid bacteria (LAB) and prebiotics can modulate the intestinal microbiota and are thought to be involved in the reduction of colorectal cancer risk. The presented study measured, using the comet assay, the antigenotoxic activity of both probiotic and non-probiotic LAB, as well as some prebiotics and the end-products of their fermentation, against fecal water (FW). The production of short chain fatty acids by the bacteria was quantified using HPLC. Seven out of the ten tested viable strains significantly decreased DNA damage induced by FW. The most effective of them were Lactobacillus mucosae 0988 and Bifidobacterium animalis ssp. lactis Bb-12, leading to a 76% and 80% decrease in genotoxicity, respectively. The end-products of fermentation of seven prebiotics by Lactobacillus casei DN 114-001 exhibited the strongest antigenotoxic activity against FW, with fermented inulin reducing genotoxicity by 75%. Among the tested bacteria, this strain produced the highest amounts of butyrate in the process of prebiotic fermentation, and especially from resistant dextrin (4.09 μM/mL). Fermented resistant dextrin improved DNA repair by 78% in cells pre-treated with 6.8 μM methylnitronitrosoguanidine (MNNG). Fermented inulin induced stronger DNA repair in cells pre-treated with mutagens (FW, 25 μM hydrogen peroxide, or MNNG) than non-fermented inulin, and the efficiency of DNA repair after 120 min of incubation decreased by 71%, 50% and 70%, respectively. The different degrees of genotoxicity inhibition observed for the various combinations of bacteria and prebiotics suggest that this effect may be attributable to carbohydrate type, SCFA yield, and the ratio of the end-products of prebiotic fermentation.

  19. Changes of fatty acid aerosol hygroscopicity induced by ozonolysis under humid conditions

    Directory of Open Access Journals (Sweden)

    O. Vesna

    2008-08-01

    Full Text Available Unsaturated fatty acids are important constituents of the organic fraction of atmospheric aerosols originating from biogenic or combustion sources. Oxidative processing of these may change their interaction with water and thus affect their effect on climate. The ozonolysis of oleic and arachidonic acid aerosol particles was studied under humid conditions in a flow reactor at ozone exposures close to atmospheric levels, at concentrations between 0.5 and 2 ppm. While oleic acid is a widely used proxy for such studies, arachidonic acid represents polyunsaturated fatty acids, which may decompose into hygroscopic products. The hygroscopic (diameter growth factor at 93% relative humidity (RH of the oxidized arachidonic particles increased up to 1.09 with increasing RH during the ozonolysis. In contrast, the growth factor of oleic acid was very low (1.03 at 93% RH and was almost invariant to the ozonolysis conditions, so that oleic acid is not a good model to observe oxidation induced changes of hygroscopicity under atmospheric conditions. We show for arachidonic acid particles that the hygroscopic changes induced by humidity during ozonolysis are accompanied by about a doubling of the ratio of carboxylic acid protons to aliphatic protons. We suggest that, under humid conditions, the reaction of water with the Criegee intermediates might open a pathway for the formation of smaller acids that lead to more significant changes in hygroscopicity. Thus the effect of water to provide a competing pathway during ozonolysis observed in this study should be motivation to include water, which is ubiquitously present in and around atmospheric particles, in future studies related to aerosol particle aging.

  20. Clavulanic acid induces penile erection and yawning in male rats: comparison with apomorphine.

    Science.gov (United States)

    Sanna, Fabrizio; Melis, Maria Rosaria; Angioni, Laura; Argiolas, Antonio

    2013-02-01

    The beta-lactamase inhibitor clavulanic acid induced penile erection and yawning in a dose dependent manner when given intraperitoneally (IP, 0.05-5mg/kg), perorally (OS, 0.1-5mg/kg) and intracereboventricularly (ICV, 0.01-5 μg/rat) to male rats. The effect resembles that of the dopamine receptor agonist apomorphine given subcutaneously (SC) (0.02-0.25mg/kg), although the responses of the latter followed a U inverted dose-response curve, disappearing at doses higher than 0.1mg/kg. Clavulanic acid responses were reduced by about 55% by haloperidol, a dopamine D2 receptor antagonist (0.1mg/kg IP), and by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist (2 μg/rat ICV), both given 15 min before clavulanic acid. A higher reduction of clavulanic acid responses (more than 80%) was also found with morphine, an opioid receptor agonist (5mg/kg IP), and with mianserin, a serotonin 5HT(2c) receptor antagonist (0.2mg/kg SC). In contrast, no reduction was found with naloxone, an opioid receptor antagonist (1mg/kg IP). The ability of haloperidol, d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin and morphine to reduce clavulanic acid induced penile erection and yawning suggests that clavulanic acid induces these responses, at least in part, by increasing central dopaminergic neurotransmission. Dopamine in turn activates oxytocinergic neurotransmission and centrally released oxytocin induces penile erection and yawning. However, since both penile erection and yawning episodes were reduced not only by the blockade of central dopamine and oxytocin receptors and by the stimulation of opioid receptors, which inhibits oxytocinergic neurotransmission, but also by mianserin, an increase of central serotonin neurotransmission is also likely to participate in these clavulanic acid responses.

  1. C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle.

    Science.gov (United States)

    Olson, Aaron K; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly Priddy, Colleen; Isern, Nancy; Portman, Michael A

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and (13)Carbon ((13)C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing (13)C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the

  2. Industrial application of selected lactic acid bacteria isolated from local semolinas for typical sourdough bread production.

    Science.gov (United States)

    Corona, Onofrio; Alfonzo, Antonio; Ventimiglia, Giusi; Nasca, Anna; Francesca, Nicola; Martorana, Alessandra; Moschetti, Giancarlo; Settanni, Luca

    2016-10-01

    Four obligate heterofermentative lactic acid bacteria (LAB) strains (Weissella cibaria PON10030 and PON10032 and Leuconostoc citreum PON 10079 and PON10080) were tested as single strain starters, mono-species dual strain starters, and multiple strain starter for the preparation and propagation of sourdoughs for the production of a typical bread at industrial level. The kinetics of pH and TTA during the daily sourdough refreshments indicated a correct acidification process for all trials. The concentration of lactic and acetic acid increased consistently during fermentation. The resulting molar ratios between these two organic acids in the experimental trials were lower than those observed in the control trial. The microbiological investigation showed levels of approximately 10(9) CFU/mL in almost all sourdoughs and the comparison of the genetic polymorphisms of the dominating LAB with those of the pure cultures evidenced the persistence of the added strains over time. The resulting breads were evaluated for several quality parameters. The breads with the greatest height were obtained with the quadruple combination of leuconostocs and weissellas. The highest softness was registered for the breads obtained from fermentations performed by W. cibaria PON10032 alone and in combination. The different inocula influenced also the color, the void fraction, the cell density and the mean cell area of the breads. Different levels of acids, alcohols, aldehydes, esters, hydrocarbons, ketones, terpenes, furans and phenol were emitted by the breads. The sensory tests indicated the breads from the sourdoughs fermented with the seven LAB inocula as sweeter and less acidic than control breads and the breads from the trials with the highest complexity of LAB inoculums were those more appreciated by tasters. A multivariate approach found strong differences among the trials. In particular, control breads and the breads obtained with different starter LAB were quite distant and a more

  3. Industrial application of selected lactic acid bacteria isolated from local semolinas for typical sourdough bread production.

    Science.gov (United States)

    Corona, Onofrio; Alfonzo, Antonio; Ventimiglia, Giusi; Nasca, Anna; Francesca, Nicola; Martorana, Alessandra; Moschetti, Giancarlo; Settanni, Luca

    2016-10-01

    Four obligate heterofermentative lactic acid bacteria (LAB) strains (Weissella cibaria PON10030 and PON10032 and Leuconostoc citreum PON 10079 and PON10080) were tested as single strain starters, mono-species dual strain starters, and multiple strain starter for the preparation and propagation of sourdoughs for the production of a typical bread at industrial level. The kinetics of pH and TTA during the daily sourdough refreshments indicated a correct acidification process for all trials. The concentration of lactic and acetic acid increased consistently during fermentation. The resulting molar ratios between these two organic acids in the experimental trials were lower than those observed in the control trial. The microbiological investigation showed levels of approximately 10(9) CFU/mL in almost all sourdoughs and the comparison of the genetic polymorphisms of the dominating LAB with those of the pure cultures evidenced the persistence of the added strains over time. The resulting breads were evaluated for several quality parameters. The breads with the greatest height were obtained with the quadruple combination of leuconostocs and weissellas. The highest softness was registered for the breads obtained from fermentations performed by W. cibaria PON10032 alone and in combination. The different inocula influenced also the color, the void fraction, the cell density and the mean cell area of the breads. Different levels of acids, alcohols, aldehydes, esters, hydrocarbons, ketones, terpenes, furans and phenol were emitted by the breads. The sensory tests indicated the breads from the sourdoughs fermented with the seven LAB inocula as sweeter and less acidic than control breads and the breads from the trials with the highest complexity of LAB inoculums were those more appreciated by tasters. A multivariate approach found strong differences among the trials. In particular, control breads and the breads obtained with different starter LAB were quite distant and a more

  4. Light induced conversion of nitrogen dioxide into nitrous acid on submicron humic acid aerosol

    Directory of Open Access Journals (Sweden)

    K. Stemmler

    2007-08-01

    Full Text Available The interactions of aerosols consisting of humic acids with gaseous nitrogen dioxide (NO2 were investigated under different light conditions in aerosol flow tube experiments at ambient pressure and temperature. The results show that NO2 is converted on the humic acid aerosol into nitrous acid (HONO, which is released from the aerosol and can be detected in the gas phase at the reactor exit. The formation of HONO on the humic acid aerosol is strongly activated by light: In the dark, the HONO-formation was below the detection limit, but it was increasing with the intensity of the irradiation with visible light. Under simulated atmospheric conditions with respect to the actinic flux, relative humidity and NO2-concentration, reactive uptake coefficients γrxn for the NO2→HONO conversion on the aerosol between γrxn <10−7 (in the dark and γrxn=6×10−6 were observed. The observed uptake coefficients decreased with increasing NO2-concentration in the range from 2.7 to 280 ppb and were dependent on the relative humidity (RH with slightly reduced values at low humidity (<20% RH and high humidity (>60% RH. The measured uptake coefficients for the NO2→HONO conversion are too low to explain the HONO-formation rates observed near the ground in rural and urban environments by the conversion of NO2→HONO on organic aerosol surfaces, even if one would assume that all aerosols consist of humic acid only. It is concluded that the processes leading to HONO formation on the Earth surface will have a much larger impact on the HONO-formation in the lowermost layer of the troposphere than humic materials potentially occurring in airborne particles.

  5. Development and characterisation of molecularly imprinted polymers based on methacrylic acid for selective recognition of drugs.

    Science.gov (United States)

    Shi, Xizhi; Wu, Aibo; Qu, Guorun; Li, Rongxiu; Zhang, Dabing

    2007-09-01

    Specific molecularly imprinted polymers (MIPs) for the drug reserpine (RES) using methacrylic acid (MAA) as the functional monomer were developed and characterised for the first time in this study. Evaluation of the various polymers by binding assays indicated that the optimum ratio of functional monomer to template was 4:1. Furthermore, the imprinting effect of the MIPs was assessed by the chromatographic method, which demonstrated that the MIPs had better chromatographic behavior and selectivity than those of the corresponding NIPs. A combination of BET, NMR, UV spectroscopy, and MISPE analyses for investigation of the imprinting and recognition properties revealed that strong specific interactions between the functional monomer and RES in the prepolymerization solutions and the aqueous solutions were probably responsible for RES recognition. The preparation of RES MIPs and elucidation of imprinting and recognition mechanisms may serve as useful references for other drug MIPs.

  6. Dendrite Spacing Selection during Directional Solidification of Pivalic Acid-Ethanol System

    Institute of Scientific and Technical Information of China (English)

    Myung-Jin Suk; Young-Min Park; Youn-Che Kim

    2008-01-01

    Unidirectional solidification of pivalic acid (PVA)-ethanol (Eth) mixture was performed to examine whether an allowable range of primary dendrite spacing definitely exists at a given growth velocity and how the range is history-dependent. PVA-0.59 wt pct Eth was unidirectionally solidified in the range of growth velocity 0.5-64 μm/s at the temperature gradient of 2.3 K/mm. Sequential change in growth velocity was imposed to determine the upper and lower limits for the allowable range of stable spacing. An allowable range of the steady state primary spacing was observed at a given growth velocity, and the extent of the range seems to be dependent on the degree to which step-increase or step-decrease in growth velocity is accomplished. As the degree of sequential change in growth velocity increases, the history-dependence of the selection for the primary dendrite spacing tends to disappear.

  7. Label-free and selective sensing of uric acid with gold nanoclusters as optical probe.

    Science.gov (United States)

    Wang, Jian; Chang, Yong; Wu, Wen Bi; Zhang, Pu; Lie, Shao Qing; Huang, Cheng Zhi

    2016-05-15

    Clinically, the amount of uric acid (UA) in biological fluids is closely related to some diseases such as hyperuricemia and gout, thus it is of great significance to sense UA in clinical samples. In this work, red gold nanoclusters (AuNCs) with relatively high fluorescence quantum yield and strong fluorescence emission were facilely available using bovine serum albumin (BSA) as template. The fluorescence of BSA-protected AuNCs can be sensitively quenched by H2O2, which is further capable of sensing UA through the specific catalytic oxidation with uricase, since it generates stoichiometric quantity of H2O2 by-product. The proposed assay allows for the selective detection of UA in the range of 10-800 μM with a detection limit of 6.6 μM, which is applicable to sense UA in clinical samples with satisfactory results, suggesting its great potential for diagnostic purposes. PMID:26992526

  8. Reaction mixtures formed by nitrite and selected sulfa-drugs showed mutagenicity in acidic medium

    Directory of Open Access Journals (Sweden)

    Claudia Trossero

    2009-01-01

    Full Text Available Nitrite, which is present in preserved meat and can be produced in the oral cavity by reduction of nitrate taken from vegetables, could react in stomach with nitrosatable drugs, giving genotoxic-carcinogenic N-nitroso compounds (NOC. The mutagenicity of reaction mixtures formed by sodium nitrite and selected sulfa-drugs (sulfathiazole, HST; phtalylsulfathiazole, PhST; complex Co(II-sulfathiazole, Co(II-ST in acidic medium was evaluated using the Salmonella typhimurium reverse mutation assay (Ames test, with TA98 and TA 100 strains. The reactions were carried out at room temperature, with a mole ratio [nitrite]/[sulfa-drug] > 1. The three reaction mixtures showed mutagenic effects in the considered range.

  9. Selective Preparation of Furfural from Xylose over Sulfonic Acid Functionalized Mesoporous Sba-15 Materials

    Directory of Open Access Journals (Sweden)

    Panpan Li

    2011-04-01

    Full Text Available Sulfonic acid functionalized mesoporous SBA-15 materials were prepared using the co-condensation and grafting methods, respectively, and their catalytic performance in the dehydration of xylose to furfural was examined. SBA-15-SO3H(C prepared by the co-condensation method showed 92–95% xylose conversion and 74% furfural selectivity, and 68–70% furfural yield under the given reaction conditions. The deactivation and regeneration of the SBA-15-SO3H(C catalyst for the dehydration of xylose was also investigated. The results indicate that the used and regeneration catalysts retained the SBA-15 mesoporous structure, and the S content of SBA-15-SO3H(C almost did not change. The deactivation of the catalysts is proposed to be associated with the accumulation of byproducts, which is caused by the loss reaction of furfural. After regeneration by H2O2, the catalytic activity of the catalyst almost recovered.

  10. Formic-acid-induced depolymerization of oxidized lignin to aromatics

    Science.gov (United States)

    Rahimi, Alireza; Ulbrich, Arne; Coon, Joshua J.; Stahl, Shannon S.

    2014-11-01

    Lignin is a heterogeneous aromatic biopolymer that accounts for nearly 30% of the organic carbon on Earth and is one of the few renewable sources of aromatic chemicals. As the most recalcitrant of the three components of lignocellulosic biomass (cellulose, hemicellulose and lignin), lignin has been treated as a waste product in the pulp and paper industry, where it is burned to supply energy and recover pulping chemicals in the operation of paper mills. Extraction of higher value from lignin is increasingly recognized as being crucial to the economic viability of integrated biorefineries. Depolymerization is an important starting point for many lignin valorization strategies, because it could generate valuable aromatic chemicals and/or provide a source of low-molecular-mass feedstocks suitable for downstream processing. Commercial precedents show that certain types of lignin (lignosulphonates) may be converted into vanillin and other marketable products, but new technologies are needed to enhance the lignin value chain. The complex, irregular structure of lignin complicates chemical conversion efforts, and known depolymerization methods typically afford ill-defined products in low yields (that is, less than 10-20wt%). Here we describe a method for the depolymerization of oxidized lignin under mild conditions in aqueous formic acid that results in more than 60wt% yield of low-molecular-mass aromatics. We present the discovery of this facile C-O cleavage method, its application to aspen lignin depolymerization, and mechanistic insights into the reaction. The broader implications of these results for lignin conversion and biomass refining are also considered.

  11. Formic-acid-induced depolymerization of oxidized lignin to aromatics.

    Science.gov (United States)

    Rahimi, Alireza; Ulbrich, Arne; Coon, Joshua J; Stahl, Shannon S

    2014-11-13

    Lignin is a heterogeneous aromatic biopolymer that accounts for nearly 30% of the organic carbon on Earth and is one of the few renewable sources of aromatic chemicals. As the most recalcitrant of the three components of lignocellulosic biomass (cellulose, hemicellulose and lignin), lignin has been treated as a waste product in the pulp and paper industry, where it is burned to supply energy and recover pulping chemicals in the operation of paper mills. Extraction of higher value from lignin is increasingly recognized as being crucial to the economic viability of integrated biorefineries. Depolymerization is an important starting point for many lignin valorization strategies, because it could generate valuable aromatic chemicals and/or provide a source of low-molecular-mass feedstocks suitable for downstream processing. Commercial precedents show that certain types of lignin (lignosulphonates) may be converted into vanillin and other marketable products, but new technologies are needed to enhance the lignin value chain. The complex, irregular structure of lignin complicates chemical conversion efforts, and known depolymerization methods typically afford ill-defined products in low yields (that is, less than 10-20wt%). Here we describe a method for the depolymerization of oxidized lignin under mild conditions in aqueous formic acid that results in more than 60wt% yield of low-molecular-mass aromatics. We present the discovery of this facile C-O cleavage method, its application to aspen lignin depolymerization, and mechanistic insights into the reaction. The broader implications of these results for lignin conversion and biomass refining are also considered.

  12. Isolation of an osmotic stress- and abscisic acid-induced gene encoding an acidic endochitinase from Lycopersicon chilense.

    Science.gov (United States)

    Chen, R D; Yu, L X; Greer, A F; Cheriti, H; Tabaeizadeh, Z

    1994-10-28

    We have identified one osmotic stress- and abscisic acid-responsive member of the endochitinase (EC 3.2.1.14) gene family from leaves of drought-stressed Lycopersicon chilense plants, a natural inhabitant of extremely arid regions in South America. The 966-bp full-length cDNA (designated pcht28) encodes an acidic chitinase precursor with an amino-terminal signal peptide. The mature protein is predicted to have 229 amino acid residues with a relative molecular mass of 24,943 and pI value of 6.2. Sequence analysis revealed that pcht28 has a high degree of homology with class II chitinases (EC 3.2.1.14) from tomato and tobacco. Expression of the pcht28 protein in Escherichia coli verified that it is indeed a chitinase. Northern blot analysis indicated that this gene has evolved a different pattern of expression from that of other family members reported thus far. It is highly induced by both osmotic stress and the plant hormone abscisic acid. Southern blot analysis of genomic DNA suggested that the pcht28-related genes may form a small multigene family in this species. The efficiency of induction of the gene by drought stress, in leaves and stems, is significantly higher in L. chilense than in the cultivated tomato. It is speculated that, besides its general defensive function, the pcht28-encoded chitinase may play a particular role in plant development or in protecting plants from pathogen attack during water stress. PMID:7816027

  13. Phosphinic acid functionalized carbon nanotubes for sensitive and selective sensing of chromium(VI)

    Energy Technology Data Exchange (ETDEWEB)

    Deep, Akash, E-mail: dr.akashdeep@csio.res.in; Sharma, Amit L.; Tuteja, Satish K.; Paul, A.K.

    2014-08-15

    Highlights: • SWCNTs have been conjugated with bis(2,4,4-trimethylpentyl) phosphinic acid (PA/d). • SWCNT-PA/d adduct is demonstrated for electrochemical sensing of Cr(VI). • Linear response is obtained for 0.01–10 ppb Cr(VI). • Sensitivity and the limit of detection are 35 ± 4 nA/ppb and 0.01 ppb, respectively. • Proposed sensing of Cr(VI) is selective with respect to many other metals. - Abstract: Single-walled carbon nanotubes (SWCNTs) have been functionalized with a phosphinic acid derivative ‘bis(2,4,4-trimethylpentyl) phosphinic acid’ (PA/d). It has been achieved by treating the chlorinated SWCNTs with PA/d at 80 °C. Successful functionalization and different nanomaterial properties have been investigated by UV–vis–NIR, FTIR, Raman spectroscopy, AFM and FE-SEM. PA/d conjugated SWCNTs (CNT–PA) are dispersible in some common organic solvents, e.g. CH{sub 2}Cl{sub 2}, DMF, CHCl{sub 3}, and THF. The ‘CNT–PA’ complex was spin-casted on boron doped silicon wafer. Thus fabricated sensing electrode is demonstrated for sensitive and selective electrochemical sensing of chromium(VI) ions. A linear response is obtained over a wide range of Cr(VI) concentration (0.01–10 ppb). The sensor's sensitivity and the limit of detection are observed to be 35 ± 4 nA/ppb and 0.01 ppb, respectively. The practical utility of the proposed sensor is demonstrated by determining the Cr(VI) concentration in an industrial effluent sample and an underground water sample.

  14. Ecosystem-specific selection of microbial ammonia oxidizers in an acid soil

    Directory of Open Access Journals (Sweden)

    M. Saiful Alam

    2013-01-01

    Full Text Available The function of ammonia-oxidizing archaea (AOA and bacteria (AOB depends on the availability of ammonia substrate and the supply of oxygen. The interactions and evolutions of AOA and AOB communities along ecological gradients of substrate availability in complex environment have been much debated, but rarely tested. In this study, two ecosystems of maize and rice crops under different fertilization regimes were selected to investigate the community diversification of soil AOA and AOB in response to long-term field fertilization and flooding management in an acid soil. Real-time quantitative PCR of amoA genes demonstrated that the abundance of AOA was significantly stimulated after conversion of upland to paddy soils, while slight decline of AOB populations was observed. DGGE fingerprints of amoA genes further revealed remarkable changes in community compositions of AOA in paddy soil when compared to upland soil. Sequencing analysis revealed that upland soil was dominated by AOA within the soil group 1.1b lineage, while the marine group 1.1a lineage predominated AOA communities in paddy soils. Irrespective of upland and paddy soils, long-term field fertilizations led to higher abundance of amoA genes of AOA and AOB than control treatment that received no fertilization, whereas archaeal amoA gene abundances outnumbered their bacterial counterpart in all samples. Phylogenetic analyses of amoA genes showed that Nitrosospira cluster 3-like AOB dominated bacterial ammonia oxidizers in both paddy and upland soils, regardless of fertilization treatments. The results of this study suggest that the marine group 1.1a AOA could be better adapted to low-oxygen environment than AOA ecotypes of the soil group 1.1b lineage, and implicate that long-term flooding as the dominant selective force driving the community diversification of AOA populations in the acid soil tested.

  15. Ecosystem-specific selection of microbial ammonia oxidizers in an acid soil

    Science.gov (United States)

    Saiful Alam, M.; Ren, G.; Lu, L.; Zheng, Y.; Peng, X.; Jia, Z.

    2013-01-01

    The function of ammonia-oxidizing archaea (AOA) and bacteria (AOB) depends on the availability of ammonia substrate and the supply of oxygen. The interactions and evolutions of AOA and AOB communities along ecological gradients of substrate availability in complex environment have been much debated, but rarely tested. In this study, two ecosystems of maize and rice crops under different fertilization regimes were selected to investigate the community diversification of soil AOA and AOB in response to long-term field fertilization and flooding management in an acid soil. Real-time quantitative PCR of amoA genes demonstrated that the abundance of AOA was significantly stimulated after conversion of upland to paddy soils, while slight decline of AOB populations was observed. DGGE fingerprints of amoA genes further revealed remarkable changes in community compositions of AOA in paddy soil when compared to upland soil. Sequencing analysis revealed that upland soil was dominated by AOA within the soil group 1.1b lineage, while the marine group 1.1a lineage predominated AOA communities in paddy soils. Irrespective of upland and paddy soils, long-term field fertilizations led to higher abundance of amoA genes of AOA and AOB than control treatment that received no fertilization, whereas archaeal amoA gene abundances outnumbered their bacterial counterpart in all samples. Phylogenetic analyses of amoA genes showed that Nitrosospira cluster 3-like AOB dominated bacterial ammonia oxidizers in both paddy and upland soils, regardless of fertilization treatments. The results of this study suggest that the marine group 1.1a AOA could be better adapted to low-oxygen environment than AOA ecotypes of the soil group 1.1b lineage, and implicate that long-term flooding as the dominant selective force driving the community diversification of AOA populations in the acid soil tested.

  16. Optimal time point for the transplantation of neural stem cells induced to differentiate with retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Shuxin Wang; Dengji Pan; Na Liu; Yongming Liu; Juan Chen; Houjie Ni; Zhouping Tang

    2011-01-01

    Previous studies have demonstrated that differentiated neural stem cells (NSCs) are more suitable for transplantation than non-differentiated NSCs. In this study, NSCs were expanded in vitro for two passages, induced with retinoic acid to differentiate, and harvested between 1-6 days later. They were subsequently cultured in artificial cerebrospinal fluid for an additional 3 days, during which their growth and morphology was monitored. NSCs induced for 4 days exhibited a peak rate of cells differentiating into neurons and robust growth. Our results indicate that the optimal time point for transplanting NSCs is following a 4-day period of induced differentiation.

  17. Direct Channeling of Retinoic Acid between Cellular Retinoic Acid-Binding Protein II and Retinoic Acid Receptor Sensitizes Mammary Carcinoma Cells to Retinoic Acid-Induced Growth Arrest

    OpenAIRE

    Budhu, Anuradha S.; Noy, Noa

    2002-01-01

    Cellular retinoic acid-binding protein II (CRABP-II) is an intracellular lipid-binding protein that associates with retinoic acid with a subnanomolar affinity. We previously showed that CRABP-II enhances the transcriptional activity of the nuclear receptor with which it shares a common ligand, namely, the retinoic acid receptor (RAR), and we suggested that it may act by delivering retinoic acid to this receptor. Here, the mechanisms underlying the effects of CRABP-II on the transcriptional ac...

  18. Characterisation of PDO olive oil Chianti Classico by non-selective (UV-visible, NIR and MIR spectroscopy) and selective (fatty acid composition) analytical techniques

    Energy Technology Data Exchange (ETDEWEB)

    Casale, M., E-mail: monica@dictfa.unige.it [Universita degli Studi di Genova, Department of Chemistry and Food and Pharmaceutical Technologies, Via Brigata Salerno 13, I-16147, Genoa (Italy); Oliveri, P.; Casolino, C. [Universita degli Studi di Genova, Department of Chemistry and Food and Pharmaceutical Technologies, Via Brigata Salerno 13, I-16147, Genoa (Italy); Sinelli, N. [Universita degli Studi di Milano, Department of Food Science and Technology, Via Celoria, 2 - I-20133 Milan (Italy); Zunin, P.; Armanino, C.; Forina, M.; Lanteri, S. [Universita degli Studi di Genova, Department of Chemistry and Food and Pharmaceutical Technologies, Via Brigata Salerno 13, I-16147, Genoa (Italy)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Characterisation of the Italian PDO extra virgin olive oil Chianti Classico. Black-Right-Pointing-Pointer Comparison between non-selective (UV-vis, NIR and MIR spectroscopy) and selective (fatty acid composition) analytical techniques. Black-Right-Pointing-Pointer Synergy among spectroscopic techniques, by the fusion of the respective spectra. Black-Right-Pointing-Pointer Prediction of the content of oleic and linoleic acids in the olive oils. - Abstract: An authentication study of the Italian PDO (protected designation of origin) extra virgin olive oil Chianti Classico was performed; UV-visible (UV-vis), Near-Infrared (NIR) and Mid-Infrared (MIR) spectroscopies were applied to a set of samples representative of the whole Chianti Classico production area. The non-selective signals (fingerprints) provided by the three spectroscopic techniques were utilised both individually and jointly, after fusion of the respective profile vectors, in order to build a model for the Chianti Classico PDO olive oil. Moreover, these results were compared with those obtained by the gas chromatographic determination of the fatty acids composition. In order to characterise the olive oils produced in the Chianti Classico PDO area, UNEQ (unequal class models) and SIMCA (soft independent modelling of class analogy) were employed both on the MIR, NIR and UV-vis spectra, individually and jointly, and on the fatty acid composition. Finally, PLS (partial least square) regression was applied on the UV-vis, NIR and MIR spectra, in order to predict the content of oleic and linoleic acids in the extra virgin olive oils. UNEQ, SIMCA and PLS were performed after selection of the relevant predictors, in order to increase the efficiency of both classification and regression models. The non-selective information obtained from UV-vis, NIR and MIR spectroscopy allowed to build reliable models for checking the authenticity of the Italian PDO extra virgin olive oil

  19. Characterisation of PDO olive oil Chianti Classico by non-selective (UV–visible, NIR and MIR spectroscopy) and selective (fatty acid composition) analytical techniques

    International Nuclear Information System (INIS)

    Highlights: ► Characterisation of the Italian PDO extra virgin olive oil Chianti Classico. ► Comparison between non-selective (UV–vis, NIR and MIR spectroscopy) and selective (fatty acid composition) analytical techniques. ► Synergy among spectroscopic techniques, by the fusion of the respective spectra. ► Prediction of the content of oleic and linoleic acids in the olive oils. - Abstract: An authentication study of the Italian PDO (protected designation of origin) extra virgin olive oil Chianti Classico was performed; UV–visible (UV–vis), Near-Infrared (NIR) and Mid-Infrared (MIR) spectroscopies were applied to a set of samples representative of the whole Chianti Classico production area. The non-selective signals (fingerprints) provided by the three spectroscopic techniques were utilised both individually and jointly, after fusion of the respective profile vectors, in order to build a model for the Chianti Classico PDO olive oil. Moreover, these results were compared with those obtained by the gas chromatographic determination of the fatty acids composition. In order to characterise the olive oils produced in the Chianti Classico PDO area, UNEQ (unequal class models) and SIMCA (soft independent modelling of class analogy) were employed both on the MIR, NIR and UV–vis spectra, individually and jointly, and on the fatty acid composition. Finally, PLS (partial least square) regression was applied on the UV–vis, NIR and MIR spectra, in order to predict the content of oleic and linoleic acids in the extra virgin olive oils. UNEQ, SIMCA and PLS were performed after selection of the relevant predictors, in order to increase the efficiency of both classification and regression models. The non-selective information obtained from UV–vis, NIR and MIR spectroscopy allowed to build reliable models for checking the authenticity of the Italian PDO extra virgin olive oil Chianti Classico.

  20. Selective local lysis and sampling of live cells for nucleic acid analysis using a microfluidic probe

    Science.gov (United States)

    Kashyap, Aditya; Autebert, Julien; Delamarche, Emmanuel; Kaigala, Govind V.

    2016-01-01

    Heterogeneity is inherent to biology, thus it is imperative to realize methods capable of obtaining spatially-resolved genomic and transcriptomic profiles of heterogeneous biological samples. Here, we present a new method for local lysis of live adherent cells for nucleic acid analyses. This method addresses bottlenecks in current approaches, such as dilution of analytes, one-sample-one-test, and incompatibility to adherent cells. We make use of a scanning probe technology - a microfluidic probe - and implement hierarchical hydrodynamic flow confinement (hHFC) to localize multiple biochemicals on a biological substrate in a non-contact, non-destructive manner. hHFC enables rapid recovery of nucleic acids by coupling cell lysis and lysate collection. We locally lysed ~300 cells with chemical systems adapted for DNA or RNA and obtained lysates of ~70 cells/μL for DNA analysis and ~15 cells/μL for mRNA analysis. The lysates were introduced into PCR-based workflows for genomic and transcriptomic analysis. This strategy further enabled selective local lysis of subpopulations in a co-culture of MCF7 and MDA-MB-231 cells, validated by characteristic E-cadherin gene expression in individually extracted cell types. The developed strategy can be applied to study cell-cell, cell-matrix interactions locally, with implications in understanding growth, progression and drug response of a tumor. PMID:27411740

  1. Inducible gene expression and environmentally regulated genes in lactic acid bacteria

    NARCIS (Netherlands)

    Kok, Jan

    1996-01-01

    Relatively recently, a number of genes and operons have been identified in lactic acid bacteria that are inducible and respond to environmental factors. Some of these genes/operons had been isolated and analysed because of their importance in the fermentation industry and, consequently, their transc

  2. Analyses on Radiation Effects in Solid Amino Acids Induced by Low Energy Fe~+ Ion Beams

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Radiation effects in Solid samples of L(+)-cysteine and L(+)-cysteine hydroehloride monohydrate induced by 110 keV Fe~+ion implantation were characterized with FTIR, ESR,HPLC and ESI-FTMS.It was validated that solid samples of the irradiated amino acids were damaged to a certain extent,and some new groups or molecular products formed.

  3. Ion-Induced Fragmentation of Amino Acids : Effect of the Environment

    NARCIS (Netherlands)

    Maclot, Sylvain; Capron, Michael; Maisonny, Remi; Lawicki, Arkadiusz; Mery, Alain; Rangama, Jimmy; Chesnel, Jean-Yves; Bari, Sadia; Hoekstra, Ronnie; Schlatholter, Thomas; Manil, Bruno; Adoui, Lamri; Rousseau, Patrick; Huber, Bernd A.

    2011-01-01

    In general, radiation-induced fragmentation of small amino acids is governed by the cleavage of the C-C(alpha) bond. We present results obtained with 300 keV Xe(20+) ions that allow molecules (glycine and valine) to be ionised at large distances without appreciable energy transfer. Also in the prese

  4. Lack of upregulation of epidermal fatty acid binding protein in dithranol induced irritation.

    NARCIS (Netherlands)

    Kucharekova, M.; Vissers, W.H.P.M.; Schalkwijk, J.; Kerkhof, P.C.M. van de; Valk, P.G.M. van der

    2003-01-01

    The exact role of epidermal fatty acid binding protein (E-FABP) in skin is unknown. A restoration of the barrier function may be associated with an upregulation of E-FABP. Moreover, E-FABP is upregulated in a variety of cells in response to oxidative stress. A recent observation that dithranol induc

  5. Salivary a-amylase protects enamel surface against acid induced softening

    DEFF Research Database (Denmark)

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend;

    -TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had...... an explanatory power of 39% in the analysis with high concentrations being most protective (pamylase on protective effect to 65...

  6. Profiling the Changes in Signaling Pathways in Ascorbic Acid/beta-Glycerophosphate-Induced Osteoblastic Differentiation

    NARCIS (Netherlands)

    Chaves Neto, Antonio Hernandes; Queiroz, Karla Cristiana; Milani, Renato; Paredes-Gamero, Edgar Julian; Justo, Giselle Zenker; Peppelenbosch, Maikel P.; Ferreira, Carmen Verissima

    2011-01-01

    Despite numerous reports on the ability of ascorbic acid and beta-glycerophosphate (AA/beta-GP) to induce osteoblast differentiation, little is known about the molecular mechanisms involved in this phenomenon. In this work, we used a peptide array containing specific consensus sequences (potential s

  7. A metallothionein mimetic peptide protects neurons against kainic acid-induced excitotoxicity

    DEFF Research Database (Denmark)

    Sonn, Katrin; Pankratova, Stanislava; Korshunova, Irina;

    2010-01-01

    the neuroprotective effect of EmtinB in the in vitro and in vivo models of kainic acid (KA)-induced neurotoxicity. We show that EmtinB passes the blood-brain barrier and is detectable in plasma for up to 24 hr. Treatment with EmtinB significantly attenuates seizures in C57BL/6J mice exposed to moderate (20 mg...

  8. STRUCTURAL REMODELING OF PROTEOGLYCANS UPON RETINOIC ACID-INDUCED DIFFERENTIATION OF NCCIT CELLS*

    Science.gov (United States)

    Gasimli, Leyla; Stansfield, Hope E.; Nairn, Alison V.; Liu, Haiying; Paluh, Janet L.; Yang, Bo; Dordick, Jonathan S.; Moremen, Kelley W.; Linhardt, Robert J.

    2012-01-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1500-fold and 2800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  9. Structural remodeling of proteoglycans upon retinoic acid-induced differentiation of NCCIT cells.

    Science.gov (United States)

    Gasimli, Leyla; Stansfield, Hope E; Nairn, Alison V; Liu, Haiying; Paluh, Janet L; Yang, Bo; Dordick, Jonathan S; Moremen, Kelley W; Linhardt, Robert J

    2013-07-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1,500-fold and 2,800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  10. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

    International Nuclear Information System (INIS)

    Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress

  11. Induced mutants of Streptococcus lactis by gamma irradiation and its effect on milk acidity

    International Nuclear Information System (INIS)

    Streptococus lactis was exposed to different doses of gamma-irradiation (10, 50, 100 and 150 Kr). The results of acidity production in sterilized milk inoculated by isolates from radiation treatments and control could be summarized in the following: 1. The mean acidity produced by S. lactis isolates after irradiation at 10 Kr increased to be 0.66% than that of control isolates (0.62%). The acidity produced by the isolates of the 50 Kr treatment showed more increment to reach the peak (0.7%). Thereafter, acidity production decreased by isolates of the 100 Kr (0.53%) and 150 Kr (0.51%) treatments. Heme, the 50 Kr treatment could be considered activation dose to S. lactis starter for acid production. 2. Two mutants were selected. Acidity production by mutant I (from 10 Kr treatment) was 0.95%, and that of mutant II (from 50 Kr treatment) was 1.0%, while acid production by the parent S. lactis culture was 0.62%. Concerning the stability of the isolates, it was found that acid production by mutant I and mutant II slightly decreased by time. The mutants were re-irradiated after 37 and 60 days at doses 10, 25 and 50 Kr. Acid production in milk by isolates of the radiation treatments was determined. The following results were obtained: -The re-irradiation of the mutants decreased the ability of the isolates for acid production than that of parent mutants. -The re-irradiation of the mutants after 60 days yielded isolates which showed more reduction in acid produced than of isolates obtained from re-irridation of the mutants after 37-days. -The higher the dose of the re-irradiation of the mutants, the lower the mean of acid production by isolates of the treatment

  12. Rapid One-Step Selection Method for Generating Nucleic Acid Aptamers: Development of a DNA Aptamer against alpha-Bungarotoxin

    DEFF Research Database (Denmark)

    Lauridsen, Lasse Holm; Shamaileh, Hadi A.; Edwards, Stacey L.;

    2012-01-01

    by PCR enrichment of the selected aptamers. One round of selection successfully identified a DNA aptamer sequence with a binding affinity of 7.58 mu M. Conclusion: We have demonstrated a one-step method for rapid production of nucleic acid aptamers. Although the reported binding affinity is in the low...... in one-step, technique is required for developing aptamers in limited time period. Principal Findings: Herein, we present a simple one-step selection of DNA aptamers against alpha-bungarotoxin. A toxin immobilized glass coverslip was subjected to nucleic acid pool binding and extensive washing followed...... micromolar range, we believe that this could be further improved by using larger targets, increasing the stringency of selection and also by combining a capillary electrophoresis separation prior to the one-step selection. Furthermore, the method presented here is a user-friendly, cheap and an easy way...

  13. Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats

    OpenAIRE

    Khairnar, Upasana; Upaganlawar, Aman; Upasani, Chandrashekhar

    2016-01-01

    Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200–250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid ...

  14. Evaluation of docosahexaenoic acid in a dog model of hypertension induced left ventricular hypertrophy.

    Science.gov (United States)

    Stanley, William C; Cox, James W; Asemu, Girma; O'Connell, Kelly A; Dabkowski, Erinne R; Xu, Wenhong; Ribeiro, Rogerio F; Shekar, Kadambari C; Hoag, Stephen W; Rastogi, Sharad; Sabbah, Hani N; Daneault, Caroline; des Rosiers, Christine

    2013-12-01

    Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16 weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs.

  15. Changes of fatty acid aerosol hygroscopicity induced by ozonolysis under humid conditions

    Directory of Open Access Journals (Sweden)

    O. Vesna

    2007-11-01

    Full Text Available Unsaturated fatty acids are important constituents of the organic fraction of atmospheric aerosols originating from biogenic or combustion sources. Oxidative processing of these may change their interaction with water and thus affect their effect on climate. The ozonolysis of oleic and arachidonic acid aerosol particles was studied under humid conditions in a flow reactor at ozone exposures close to atmospheric levels, at concentrations between 0.5 and 2 ppm. While oleic acid is a widely used proxy for such studies, arachidonic acid represents polyunsaturated fatty acids, which may decompose into hygroscopic products. The hygroscopic (diameter growth factor at 93% relative humidity (RH of the oxidized arachidonic particles increased up to 1.09 with increasing RH during the ozonolysis. In contrast, the growth factor of oleic acid was very low (1.03 at 93% RH and was almost invariant to the ozonolysis conditions, so that oleic acid is not a good model to observe oxidation induced changes of hygroscopicity under atmospheric conditions. We show for arachidonic particles that the hygroscopic changes induced by humidity during ozonolysis are accompanied by about a doubling of the ratio of carboxylic acid to aliphatic functional groups. We suggest that, under humid conditions, the reaction of water with the Criegee intermediates might open a pathway for the formation of smaller acids that lead to more significant changes in hygroscopicity. Thus the effect of water to provide a competing pathway during ozonolysis observed in this study should be motivation to include water, which is ubiquitously present in and around atmospheric particles, in future studies related to aerosol particle aging.

  16. Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides

    OpenAIRE

    Park, Jung-Min; Higuchi, Tsunehiko; Kikuchi, Kazuya; Urano, Yasuteru; Hori, Hiroyuki; Nishino, Takeshi; Aoki, Junken; Inoue, Keizo; Nagano, Tetsuo

    2001-01-01

    The aim of this study was to investigate the structure-activity relationship of S-alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of these compounds on cytokine-induced NO production by human DLD-1 cells.In an in vitro assay, S-methyl-L-isothiocitrulline (L-MIT) was slightly selective for human neuronal NOS (nNOS) over the inducible (iNOS) or endothelial (eNOS) isozyme, but the comb...

  17. Non-gated laser-induced breakdown spectroscopy in bulk water by position-selective detection

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Ye; Xue, Boyang; Song, Jiaojian; Lu, Yuan; Zheng, Ronger, E-mail: rzheng@ouc.edu.cn [Optics and Optoelectronics Laboratory, Ocean University of China, Qingdao 266100 (China)

    2015-09-14

    Temporal and spatial evolutions of the laser-induced plasma in bulk water are investigated using fast imaging and emission spectroscopic techniques. By tightly focusing a single-pulse nanosecond Nd: YAG laser beam into the bulk water, we generate a strongly expanded plasma with high reproducibility. Such a strong expanding plasma enables us to obtain well-resolved spectral lines by means of position-selective detection; hence, the time-gated detector becomes abdicable. The present results suggest not only a possible non-gated approach for underwater laser-induced breakdown spectroscopy but also give an insight into the plasma generation and expansion in bulk water.

  18. Involvement of Polyamine Oxidase in Abscisic Acid induced Cytosolic Antioxidant Defense in Leaves of Maize

    Institute of Scientific and Technical Information of China (English)

    Beibei Xue; Aying Zhang; Mingyi Jiang

    2009-01-01

    Using pharmacological and biochemical approaches, the role of maize polyamine oxidase (MPAO) in abscisic acid (ABA)induced antioxidant defense in leaves of maize (Zea mays L.) plants was investigated. Exogenous ABA treatment enhanced the expression of the MPAO gene and the activities of apoplastic MPAO. Pretreatment with two different inhibitors for apoplastic MPAO partly reduced hydrogen peroxide (H2O2) accumulation induced by ABA and blocked the ABA-induced expression of the antioxidant genes superoxide dismutase 4 and cytosolic ascorbate peroxidase and the activities of the cytosolic antioxidant enzymes. Treatment with spermidine, the optimum substrate of MPAO, also induced the expression and the activities of the antioxidant enzymes, and the upregulation of the antioxidant enzymes was prevented by two inhibitors of MPAO and two scavengers of H2O2. These results suggest that MPAO contributes to ABA-induced cytosolic antioxidant defense through H2O2, a Spd catabolic product.

  19. Selection of enhanced antimicrobial activity posing lactic acid bacteria characterised by (GTG)5-PCR fingerprinting.

    Science.gov (United States)

    Šalomskienė, Joana; Abraitienė, Asta; Jonkuvienė, Dovilė; Mačionienė, Irena; Repečkienė, Jūratė

    2015-07-01

    The aim of the study was a detail evaluation of genetic diversity among the lactic acid bacteria (LAB) strains having an advantage of a starter culture in order to select genotypically diverse strains with enhanced antimicrobial effect on some harmfull and pathogenic microorganisms. Antimicrobial activity of LAB was performed by the agar well diffusion method and was examined against the reference strains and foodborne isolates of Bacillus cereus, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. Antifungal activity was tested against the foodborne isolates of Candida parapsilosis, Debaromyces hansenii, Kluyveromyces marxianus, Pichia guilliermondii, Yarowia lipolytica, Aspergillus brasiliensis, Aspergillus versicolor, Cladosporium herbarum, Penicillium chrysogenum and Scopulariopsis brevicaulis. A total 40 LAB strains representing Lactobacillus (23 strains), Lactococcus (13 strains) and Streptococcus spp. (4 strains) were characterised by repetitive sequence based polymerase chain reaction fingerprinting which generated highly discriminatory profiles, confirmed the identity and revealed high genotypic heterogeneity among the strains. Many of tested LAB demonstrated strong antimicrobial activity specialised against one or few indicator strains. Twelve LAB strains were superior in suppressing growth of the whole complex of pathogenic bacteria and fungi. These results demonstrated that separate taxonomic units offered different possibilities of selection for novel LAB strains could be used as starter cultures enhancing food preservation.

  20. Selection of enhanced antimicrobial activity posing lactic acid bacteria characterised by (GTG)5-PCR fingerprinting.

    Science.gov (United States)

    Šalomskienė, Joana; Abraitienė, Asta; Jonkuvienė, Dovilė; Mačionienė, Irena; Repečkienė, Jūratė

    2015-07-01

    The aim of the study was a detail evaluation of genetic diversity among the lactic acid bacteria (LAB) strains having an advantage of a starter culture in order to select genotypically diverse strains with enhanced antimicrobial effect on some harmfull and pathogenic microorganisms. Antimicrobial activity of LAB was performed by the agar well diffusion method and was examined against the reference strains and foodborne isolates of Bacillus cereus, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. Antifungal activity was tested against the foodborne isolates of Candida parapsilosis, Debaromyces hansenii, Kluyveromyces marxianus, Pichia guilliermondii, Yarowia lipolytica, Aspergillus brasiliensis, Aspergillus versicolor, Cladosporium herbarum, Penicillium chrysogenum and Scopulariopsis brevicaulis. A total 40 LAB strains representing Lactobacillus (23 strains), Lactococcus (13 strains) and Streptococcus spp. (4 strains) were characterised by repetitive sequence based polymerase chain reaction fingerprinting which generated highly discriminatory profiles, confirmed the identity and revealed high genotypic heterogeneity among the strains. Many of tested LAB demonstrated strong antimicrobial activity specialised against one or few indicator strains. Twelve LAB strains were superior in suppressing growth of the whole complex of pathogenic bacteria and fungi. These results demonstrated that separate taxonomic units offered different possibilities of selection for novel LAB strains could be used as starter cultures enhancing food preservation. PMID:26139877

  1. Synthesis of Au/Graphene Oxide Composites for Selective and Sensitive Electrochemical Detection of Ascorbic Acid

    Science.gov (United States)

    Song, Jian; Xu, Lin; Xing, Ruiqing; Li, Qingling; Zhou, Chunyang; Liu, Dali; Song, Hongwei

    2014-12-01

    In this work, we present a novel ascorbic acid (AA) sensor applied to the detection of AA in human sera and pharmaceuticals. A series of Au nanoparticles (NPs) and graphene oxide sheets (Au NP/GO) composites were successfully synthesized by reduction of gold (III) using sodium citrate. Then the Au NP/GO composites were used to construct nonenzymatic electrodes in practical AA measurement. The electrode that has the best performance presents attractive analytical features, such as a low working potential of +0.15 V, a high sensitivity of 101.86 μA mM-1 cm-2 to AA, a low detection limit of 100 nM, good reproducibility and excellent selectivity. And more,it was also employed to accurately and practically detect AA in human serum and clinical vitamin C tablet with the existence of some food additive. The enhanced AA electrochemical properties of the Au NP/GO modified electrode in our work can be attributed to the improvement of electroactive surface area of Au NPs and the synergistic effect from the combination of Au NPs and GO sheets. This work shows that the Au NP/GO/GCEs hold the prospect for sensitive and selective determination of AA in practical clinical application.

  2. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    International Nuclear Information System (INIS)

    Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

  3. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Isales, Gregory M.; Hipszer, Rachel A.; Raftery, Tara D. [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States); Chen, Albert; Stapleton, Heather M. [Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, NC (United States); Volz, David C., E-mail: volz@mailbox.sc.edu [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States)

    2015-04-15

    Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

  4. Ursodeoxycholic acid suppresses mitochondria-dependent programmed cell death induced by sodium nitroprusside in SH-SY5Y cells

    International Nuclear Information System (INIS)

    Although ursodeoxycholic acid (UDCA) and its highly water-soluble formula (Yoo's solution; YS) have been shown to prevent neuronal damage, the effects of UDCA or YS against Parkinson's disease (PD)-related dopaminergic cell death has not been studied. This study investigated the protective effects of UDCA and YS on sodium nitroprusside (SNP)-induced cytotoxicity in human dopaminergic SH-SY5Y cells. Both UDCA (50–200 μM) and YS (100–200 μM) dose-dependently prevented SNP (1 mM)-induced cell death. Results showed that both UDCA and YS effectively attenuated the production of total reactive oxygen species (ROS), peroxynitrite (ONOO−) and nitric oxide (NO), and markedly inhibited the mitochondrial membrane potential (MMP) loss and intracellular reduced glutathione (GSH) depletion. SNP-induced programmed cell death events, such as nuclear fragmentation, caspase-3/7 and -9 activation, Bcl-2/Bax ratio decrease, and cytochrome c release, were significantly attenuated by both UDCA and YS. Furthermore, selective inhibitor of phosphatidylinositiol-3-kinase (PI3K), LY294002, and Akt/PKB inhibitor, triciribine, reversed the preventive effects of UDCA on the SNP-induced cytotoxicity and Bax translocation. These results suggest that UDCA can protect SH-SY5Y cells under programmed cell death process by regulating PI3K-Akt/PKB pathways.

  5. Temperature-Dependent Nanofabrication on Silicon by Friction-Induced Selective Etching.

    Science.gov (United States)

    Jin, Chenning; Yu, Bingjun; Xiao, Chen; Chen, Lei; Qian, Linmao

    2016-12-01

    Friction-induced selective etching provides a convenient and practical way for fabricating protrusive nanostructures. A further understanding of this method is very important for establishing a controllable nanofabrication process. In this study, the effect of etching temperature on the formation of protrusive hillocks and surface properties of the etched silicon surface was investigated. It is found that the height of the hillock produced by selective etching increases with the etching temperature before the collapse of the hillock. The temperature-dependent selective etching rate can be fitted well by the Arrhenius equation. The etching at higher temperature can cause rougher silicon surface with a little lower elastic modulus and hardness. The contact angle of the etched silicon surface decreases with the etching temperature. It is also noted that no obvious contamination can be detected on silicon surface after etching at different temperatures. As a result, the optimized condition for the selective etching was addressed. The present study provides a new insight into the control and application of friction-induced selective nanofabrication. PMID:27119157

  6. Protective effects of catecholomic acid derivatives on radiation-induced damage of rat liver mitochondria

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of catecholomic acid derivatives 9501, 9502 and 7601 (CBMIDA) against radiation-induced injury of rat liver mitochondria in vitro. Methods: The injury of rat liver mitochondria was induced by γ-irradiation in vitro. The contents of MDA were assayed by spectrophotometry of TBA. The absorption value at 520 nm was measured to detect swelling of mitochondria. The electron microscopic samples of mitochondria were prepared. Results: All 9501 (5 x 10-6 mol/L), 9502(10-5 mol/L), and 7601 (10-5 mol/L) significantly inhibited radiation-induced increase of MDA information.The swelling of mitochondria induced by irradiation was also prevented by 9501, 7601. The electron micrographs also showed that 9501 markedly reduced the pathological damage of mitochondria induced by γ-irradiation. The mechanisms of anti-oxidative action of catecholomic acid derivatives was discussed. Conclusion: Injurious effect of radiation on rat liver mitochondria can be prevented by catecholomic acid derivatives 9501, 9502 and 7601 (CBMIDA)

  7. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O' Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  8. Heat Stress Nephropathy From Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy.

    Science.gov (United States)

    Roncal-Jimenez, Carlos; García-Trabanino, Ramón; Barregard, Lars; Lanaspa, Miguel A; Wesseling, Catharina; Harra, Tamara; Aragón, Aurora; Grases, Felix; Jarquin, Emmanuel R; González, Marvin A; Weiss, Ilana; Glaser, Jason; Sánchez-Lozada, Laura G; Johnson, Richard J

    2016-01-01

    Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention.

  9. Radioprotective effects of kojic acid against mortality induced by gamma irradiation in mice

    International Nuclear Information System (INIS)

    To evaluate the protective effects of kojic acid on mortality induced by gamma irradiation in mice. The efficacy was compared with amifostine as a reference radioprotector. This experimental study was conducted in the Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari and Babolsar Radiotherapy Hospital, Babolsar, Iran, between October 2006 and January 2008. Kojic acid was administrated subcutaneously as single doses of 142, 175, 232, and 350 mg/kg, one hour prior to a lethal dose of gamma irradiation (8 Gy). Amifostine was injected subcutaneously at a dose of 200 mg/kg at a similar irradiation dose. The mortality was recorded 30 days after irradiation. The antioxidant activity of the kojic acid was assessed using the 1, 1-diphenyl-2-picrylhydrazyl free stable radical (DPPH) method. One hundred and twenty NMRI mice were divided into 6 groups with 20 mice in each group. At 30 days after treatment, the percentage of survival in each group was: control, 5%; 142 mg/kg, 5%; 175 mg/kg, 0%; 232 mg/kg, 30%; 350 mg/kg, 40%; and amifostine, 40% one hour treatment prior gamma irradiation. The survival rate was statistically increased in animals treated with kojic acid (350 mg/kg), one hour prior irradiation, as compared with the irradiated control group. Kojic acid exhibited concentration-dependent scavenging activity on DPPH possessing strong antioxidant activity. Kojic acid with antioxidant activity reduced the mortality induced by gamma irradiation. (author)

  10. Synthesis of new isoxazoline-based acidic amino acids and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Pinto, Andrea; Conti, Paola; Grazioso, Giovanni;

    2011-01-01

    The synthesis of four new isoxazoline-based amino acids being analogues of previously described glutamate receptor ligands is reported and their affinity for ionotropic glutamate receptors is analyzed in comparison with that of selected model compounds. Molecular modelling investigations have bee...

  11. Sulfur Amino Acids in Diet-induced Fatty Liver: A New Perspective Based on Recent Findings

    Directory of Open Access Journals (Sweden)

    John I. Toohey

    2014-06-01

    Full Text Available The relationship of sulfur amino acids to diet-induced fatty liver was established 80 years ago, with cystine promoting the condition and methionine preventing it. This relationship has renewed importance today because diet-induced fatty liver is relevant to the current epidemics of obesity, non-alcoholic fatty liver disease, metabolic syndrome, and type 2 diabetes. Two recent papers provide the first evidence linking sulfane sulfur to diet-induced fatty liver opening a new perspective on the problem. This review summarizes the early data on sulfur amino acids in fatty liver and correlates that data with current knowledge of sulfur metabolism. Evidence is reviewed showing that the lipotropic effect of methionine may be mediated by sulfane sulfur and that the hepatosteatogenic effect of cystine may be related to the removal of sulfane sulfur by cysteine catabolites. Possible preventive and therapeutic strategies are discussed.

  12. Salicylic acid inhibits UV- and Cis-Pt-induced human immunodeficiency virus expression

    International Nuclear Information System (INIS)

    Previous studies have shown that exposure of HeLa cells stably transfected with a human immunodeficiency virus-long terminal repeat-chloramphenicol acetyl transferase (HIV-LTR-CAT) construct to UV light-induced expression from the HIV LTR. By culturing the cells with salicylic acid we demonstrated dose-dependent repression of this induced HIV expression. Repression was evident if salicylic acid was administered 2 h before, at the same time as, or up to 6 h after exposure to the DNA-damaging agent. The kinetics were similar for UV- and for cis-Pt-induced HIV expression, and induction was dependent on the UV dose or cis-Pt concentration added to the culture. These results suggest a role for the prostaglandins or the cyclooxygenase pathway or both in HIV induction mediated by DNA-damaging agents

  13. Effect of Tanshitone on prevention and treatment of retinoic acid-induced osteoporosis in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yan-meng; LIU Yu-bo; GAO Yun-sheng

    2008-01-01

    Objective To observe the prevention and therapeutic effects of tanshitone (TAN) on retinoic acid induced osteoporosis in mice. Methods The mice osteoporosis was induced by given retinoic acid intragasttrically for two weeks. The histomorphological features of bone were observed and biochemical indexes in serum (Ca, P, ALP, TRAP, E2, BGP) were determined after mice were given TAN at the dose of 40, 80, 160 mg·kg-1 respectively. Results Tanshitone can induce high conversion of osteoporosis. The levels of P, ALP, TRAP and BGP in the TAN groups were lower than the model group, while the E2 level was higher than the model group. Conclusions Tanshitone can prevent the loss bone in the experimental mice. The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

  14. Inducing dopaminergic differentiation of expanded rat mesencephalic neural stem cells by ascorbic acid in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHENG Min; WANG Dongmei; HOU Lingling; LI Haimin; XIE Chao; JIAO Wencang; BAI Cixian; WANG Yaping; PEI Xuetao

    2004-01-01

    Ascorbic acid (AA) induced differentiation of neural stem cells (NSCs) into dopaminergic (DAergic) neurons is reported.NSCs derived from rat mesencephalon were maintained and expanded in a defined medium containing mitogens of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF).Compared with the control, ascorbic acid treatment led to more DAergic neuronal differentiation as indicated by the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT), which are specific markers of dopamine neurons.AA induction also enhanced expression of Nurr1 and Shh.PD98059, an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, could block AA-induced Nurr1, TH and DAT mRNA expression.The results might suggest a new strategy to provide enough dopaminergic cells for the therapy of Parkinson's disease (PD), and Nurr1 and ERK signaling pathway might participate in the AA-induced DAergic differentiation.

  15. Phytic acid suppresses ischemia-induced hydroxyl radical generation in rat myocardium.

    Science.gov (United States)

    Obata, Toshio; Nakashima, Michiko

    2016-03-01

    The present study examined whether ischemia-reperfusion-induced hydroxyl radical (·OH) generation was attenuated by myo-inositol hexaphosphoric acid (phytic acid). A flexibly mounted microdialysis technique was used to detect the generation of ·OH in in vivo rat hearts. To measure the level of ·OH, sodium salicylate in Ringer's solution (0.5mM or 0.5 nmol/μl/min) was infused directly through a microdialysis probe to detect the generation of ·OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). To confirm the generation of ·OH by Fenton-type reaction, iron(II) was infused through a microdialysis probe. A positive linear correlation between iron(II) and the formation of 2,3-DHBA (R(2)=0.983) was observed. However, the level of 2,3-DHBA in norepinephrine (100 μM) plus phytic acid (100 μM) treated group were significantly lower than those observed in norepinephrine-only-treated group (n=6, *p<0.05). To examine the effect of phytic acid on ischemia-reperfusion-induced ·OH generation, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, the normal elevation of 2,3-DHBA in the heart dialysate was not observed in animals pretreated with phytic acid. These results suggest that phytic acid is associated with antioxidant effect due to the suppression of iron-induced ·OH generation.

  16. Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei

    International Nuclear Information System (INIS)

    Folic acid deficiency can lead to uracil incorporation into DNA, hypomethylation of DNA, inefficient DNA repair and increase chromosome malsegregation and breakage. Because ionising radiation increases demand for efficient DNA repair and also causes chromosome breaks we hypothesised that folic acid deficiency may increase sensitivity to radiation-induced chromosome breakage. We tested this hypothesis by using the cytokinesis-block micronucleus assay in 10 day WIL2-NS cell cultures at four different folic acid concentrations (0.2, 2, 20, and 200 nM) that span the 'normal' physiological range in humans. The study showed a significant dose-dependent increase in frequency of binucleated cells with micronuclei and/or nucleoplasmic bridges with decreasing folic acid concentration (P < 0.0001, P = 0.028, respectively). These biomarkers of chromosomal instability were also increased in cells irradiated (1.5 Gy γ-rays) on day 9 relative to un-irradiated controls (P < 0.05). Folic acid deficiency and γ-irradiation were shown to have a significant interactive effect on frequency of cells containing micronuclei (two-way ANOVA, interaction P 0.0039) such that the frequency of radiation-induced micronucleated cells (i.e. after subtracting base-line frequency of un-irradiated controls) increased with decreasing folic acid concentration (P-trend < 0.0001). Aneuploidy of chromosome 21, apoptosis and necrosis were increased by folic acid deficiency but not by ionising radiation. The results of this study show that folate status has an important impact on chromosomal stability and is an important modifying factor of cellular sensitivity to radiation-induced genome damage

  17. Phytic acid suppresses ischemia-induced hydroxyl radical generation in rat myocardium.

    Science.gov (United States)

    Obata, Toshio; Nakashima, Michiko

    2016-03-01

    The present study examined whether ischemia-reperfusion-induced hydroxyl radical (·OH) generation was attenuated by myo-inositol hexaphosphoric acid (phytic acid). A flexibly mounted microdialysis technique was used to detect the generation of ·OH in in vivo rat hearts. To measure the level of ·OH, sodium salicylate in Ringer's solution (0.5mM or 0.5 nmol/μl/min) was infused directly through a microdialysis probe to detect the generation of ·OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). To confirm the generation of ·OH by Fenton-type reaction, iron(II) was infused through a microdialysis probe. A positive linear correlation between iron(II) and the formation of 2,3-DHBA (R(2)=0.983) was observed. However, the level of 2,3-DHBA in norepinephrine (100 μM) plus phytic acid (100 μM) treated group were significantly lower than those observed in norepinephrine-only-treated group (n=6, *pphytic acid on ischemia-reperfusion-induced ·OH generation, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, the normal elevation of 2,3-DHBA in the heart dialysate was not observed in animals pretreated with phytic acid. These results suggest that phytic acid is associated with antioxidant effect due to the suppression of iron-induced ·OH generation. PMID:26724394

  18. Selective extraction of derivates of p-hydroxy-benzoic acid from plant material by using a molecularly imprinted polymer.

    Science.gov (United States)

    Karasová, Gabriela; Lehotay, Jozef; Sádecká, Jana; Skacáni, Ivan; Lachová, Miroslava

    2005-12-01

    Selective SPE of derivates of p-hydroxybenzoic acid (pHBA) from plant extract of Melissa officinalis is presented using a molecularly imprinted polymer (MIP) made with protocatechuic acid (PA) as template molecule. MIP was prepared with acrylamide as functional monomer, ethylene glycol dimethacrylate as crosslinking monomer and ACN as porogen. MIP was evaluated towards six phenolic acids: PA, gallic acid, pHBA, vanillic acid (VA), gentisic acid (GeA) and syringic acid (SyrA), and then steps of molecularly imprinted SPE (MISPE) procedure were optimized. The best specific binding capacity of MIP was obtained for PA in ACN (34.7 microg/g of MIP). Other tested acids were also bound on MIP if they were dissolved in this solvent. ACN was chosen as solvent for sample application. M. officinalis was extracted into methanol/water (4:1, v/v), the extract was then evaporated to dryness and dissolved in ACN before application on MIP. Water and ACN were used as washing solvents and elution of benzoic acids was performed by means of a mixture methanol/acetic acid (9:1, v/v). pHBA, GA, PA and VA were extracted with recoveries of 56.3-82.1% using this MISPE method. GeA was not determined in plant extract. PMID:16405176

  19. Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Marchetti, Christine M;

    2010-01-01

    The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans.......The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans....

  20. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J;

    2001-01-01

    The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mi...

  1. Preparation of magnetic dummy molecularly imprinted polymers for selective extraction and analysis of salicylic acid in Actinidia chinensis.

    Science.gov (United States)

    You, Qing-Ping; Peng, Mi-Jun; Zhang, Yu-Ping; Guo, Jun-Fang; Shi, Shu-Yun

    2014-01-01

    Compounds with strong intramolecular hydrogen bonds (e.g., salicylic acid) have weak intermolecular hydrogen bonding interactions between them and functional monomers in the imprinting process. Consequently, the corresponding molecularly imprinted polymers (MIPs) have no specific adsorption ability. Here, the first magnetic dummy MIPs (MDMIPs) based on benzonic acid as dummy template are successfully developed and evaluated with respect to the applications in selective enrichment and analysis of salicylic acid from complex mixtures. Various parameters affecting absorption/desorption were evaluated for achieving optimal recovery and reducing nonspecific interactions. The prepared MDMIPs showed high adsorption capacity, good selectivity, rapid kinetic binding (40 min) and magnetic separation (5 s), high reproducibility (RSDsalicylic acid was quantified (0.2 μg/g of fresh mass) in Actinidia chinensis by high-performance liquid chromatography.

  2. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    Science.gov (United States)

    Di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-01-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation. PMID:26567894

  3. Preparation of molecularly imprinted polymers based on magnetic nanoparticles for the selective extraction of protocatechuic acid from plant extracts.

    Science.gov (United States)

    Xie, Xiaoyu; Wei, Fen; Chen, Liang; Wang, Sicen

    2015-03-01

    In this study, highly selective core-shell molecularly imprinted polymers on the surface of magnetic nanoparticles were prepared using protocatechuic acid as the template molecule. The resulting magnetic molecularly imprinted polymers were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and vibrating sample magnetometry. The binding performances of the prepared materials were evaluated by static and selective adsorption. The binding isotherms were obtained for protocatechuic acid and fitted by the Langmuir isotherm model and Freundlich isotherm model. Furthermore, the resulting materials were used as the solid-phase extraction materials coupled to high-performance liquid chromatography for the selective extraction and detection of protocatechuic acid from the extracts of Homalomena occulta and Cynomorium songaricum with the recoveries in the range 86.3-102.2%. PMID:25641806

  4. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    Science.gov (United States)

    di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-11-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation.

  5. Origin of high oxide to nitride polishing selectivity of ceria-based slurry in the presence of picolinic acid

    Institute of Scientific and Technical Information of China (English)

    Wang Liang-Yong; Liu Bo; Song Zhi-Tang; Liu Wei-Li; Feng Song-Lin; David Huang; S.V Babu

    2011-01-01

    We report on the investigation of the origin of high oxide to nitride polishing selectivity of ceria-based slurry in the presence of picolinic acid. The oxide to nitride removal selectivity of the ceria slurry with picolinic acid is as high as 76.6 in the chemical mechanical polishing. By using zeta potential analyzer, particle size analyzer, horizon profilometer, thermogravimetric analysis and Fourier transform infrared spectroscopy, the pre-and the post-polished wafer surfaces as well as the pre-and the post-used ceria-based slurries are compared. Possible mechanism of high oxide to nitride selectivity with using ceria-based slurry with picolinic acid is discussed.

  6. Folic acid supplementation attenuates hyperhomocysteinemia-induced preeclampsia-like symptoms in rats

    Institute of Scientific and Technical Information of China (English)

    Jun Wang; Yan Cui; Jing Ge; Meijing Ma

    2012-01-01

    Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups.

  7. Kinetics Studies on citric acid production by gamma ray induced mutant of Aspergillus niger

    International Nuclear Information System (INIS)

    Effect of cultural pH and incubation temperature on citric acid yield and kinetic patterns of citric acid fermentation by a natural isolate of aspergillus niger as CA16 and one of its gamma ray induced mutants were studied using cane molasses as growth and fermentation substrate. Mutant strain, 277/30 gave maximum citric acid yield of 85 g/l at pH 3.5 and 28 degree centigrade in molasses medium adjusted to 16% sugar and 25% prescott salt in the medium. Parent strain, CA16 gave a maximum yield of 34 g/l at pH 4.0 and 26 degree centigrade in molasses medium adjusted to 16% sugar and 100% prescott salt in the medium. In kinetic studies, strains showed combination kinetics of citric acid fermentation where product formation is directly related to growth and cell mass and indirectly related to carbohydrate uptake

  8. Time-resolved laser-induced fluorescence of UO22+ in nitric acid solutions

    International Nuclear Information System (INIS)

    A comparison between nitrogen and tripled Nd-YAG laser source for Time-Resolved Laser-Induced Fluorescence (TRLIF) of uranium in nitric acid solutions in the framework of on-line feasibility has been performed. Hence, for uranium on-line monitoring with fiber optics, nitrogen laser (337 nm), most usual source in TRLIF has several drawback; poor beam quality and non negligible nitric acid absorption at 337 nm. Tripled Nd-YAG laser (355 nm) despite lower uranium absorption coefficient has several advantages: no influence of nitric acid absorption, better beam quality, better fiber transmission and solid state technology. No significant difference for fluorescence spectra and lifetimes are observed for both lasers. Limit of detection for direct determination of uranium in nitric acid by TRLIF is in the μg/l (10-8 M) range for both lasers. (author)

  9. Indole/triazole conjugates are selective inhibitors and inducers of bacterial biofilms †

    OpenAIRE

    Minvielle, Marine J.; Bunders, Cynthia A.; Melander, Christian

    2013-01-01

    Herein is described a method of accessing indole/triazole and benzothiophene/triazole analogues that selectively promote or inhibit biofilm formation by Gram-positive and Gram-negative bacteria. Structure/function studies revealed that the addition of a bromine atom at the 2-position of the indole/triazole scaffold altered activity against both Gram-negative and Gram-positive bacteria and could transform a biofilm inhibitor into a biofilm inducer. Isosteric replacement of the indole core by a...

  10. Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.

    OpenAIRE

    Saito, H; Hatake, K.; Dvorak, A. M.; Leiferman, K M; Donnenberg, A D; Arai, N.; Ishizaka, K; Ishizaka, T

    1988-01-01

    Effects of recombinant human interleukins on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical-cord blood and bone marrow. The results showed that interleukin 5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with interleukin 5, essentially all nonadherent cells in both bone marrow and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with interleukin 4 resulted in ...

  11. Effects of L-glutamine on acetylsalycylic acid induced gastric lesions and acid back diffusion in dogs.

    Science.gov (United States)

    Hung, C R; Takeuchi, K; Okabe, S; Murata, T; Takagi, K

    1976-12-01

    Effects of L-glutamine on acetylsalicylic acid (ASA)-induced gastric mucosal lesions were studied in mongrel dogs. It was confirmed that when oral ASA at 1.0 or 2.0 g per dog is given in two divided doses, there is severe and consistent dose-dependent mucosal damage in the glandular portion of the stomach in fasted dogs. However, when L-glutamine 2.0 or 4.0 g per dog in two divided doses is given concomitantly with ASA 2.0 g per dog orally, the gastric irritation is significantly inhibited. Instillation of 20 mM of ASA in 100 mM HCl solution into the Heidenhain pouch of Beagle dogs produced a significant loss of H+ from the pouch and a gain of Na+ in the lumen compared with ASA-free controls. When L-glutamine (100 mM) was given concomitantly with ASA (20 mM) into the pouch, changes of electrolyte fluxes in response to ASA alone were significantly suppressed. However, 50 mM of L-glutamine had no appreciable effect on acid back diffusion caused by ASA 20 mM. The amino acid itself had little effect on the ionic movement in the pouch. Gross bleeding from the pouch treated with ASA was never observed with the concomitant dosing of ASA and L-glutamine 50 or 100 mM. PMID:15154

  12. Selection of lactic acid bacteria isolated from Tunisian cereals and exploitation of the use as starters for sourdough fermentation.

    Science.gov (United States)

    Mamhoud, Asma; Nionelli, Luana; Bouzaine, Taroub; Hamdi, Moktar; Gobbetti, Marco; Rizzello, Carlo Giuseppe

    2016-05-16

    Wheat bread is the most popular staple food consumed in Tunisia and, despite the niche production of some typical breads (e.g. Tabouna, Mlawi, Mtabga), the major part is currently produced with baker's yeast at industrial or, mainly, at artisanal level, while the use of sourdough fermentation is rarely reported. Considering the growing national demand for cereal baked goods, it can be hypothesized that sourdough fermentation through the use of selected lactic acid bacteria as starters could improve the overall quality and the diversification of local products. Different cereal grains were collected from the regions of Ariana, Bizerta, Beja Nabeul, and Seliana, and the autochthonous lactic acid bacteria were isolated, identified, characterized and selected on the basis of the kinetics of acidification, the proteolytic activity, and the quotient of fermentation. Lactobacillus curvatus MA2, Pediococcus pentosaceus OA2, and Pediococcus acidilactici O1A1 were used together as mixed starter to obtain a selected sourdough. According to the backslopping procedure, a type I sourdough was made from a Tunisian flour (spontaneous sourdough). Compared to the use of the spontaneous sourdough, the one obtained with selected and mixed starters by a unique fermentation step, favored the increase of the concentrations of organic acids, phenols, and total free amino acids, the most suitable quotient of fermentation, and the most intense phytase and antioxidant activities, that increased ca. 20% compared to the control. Moreover, the selected starters improved the in vitro protein digestibility (ca. 82% when selected sourdough was used), textural and sensory features of the breads, as determined by textural profile analysis and panel test, respectively. This study aimed at exploiting the potential of selected autochthonous lactic acid bacteria and extending the use of a sourdough (type II), thanks to the set-up of a two-step fermentation protocol designed for application at the

  13. Selection of lactic acid bacteria isolated from Tunisian cereals and exploitation of the use as starters for sourdough fermentation.

    Science.gov (United States)

    Mamhoud, Asma; Nionelli, Luana; Bouzaine, Taroub; Hamdi, Moktar; Gobbetti, Marco; Rizzello, Carlo Giuseppe

    2016-05-16

    Wheat bread is the most popular staple food consumed in Tunisia and, despite the niche production of some typical breads (e.g. Tabouna, Mlawi, Mtabga), the major part is currently produced with baker's yeast at industrial or, mainly, at artisanal level, while the use of sourdough fermentation is rarely reported. Considering the growing national demand for cereal baked goods, it can be hypothesized that sourdough fermentation through the use of selected lactic acid bacteria as starters could improve the overall quality and the diversification of local products. Different cereal grains were collected from the regions of Ariana, Bizerta, Beja Nabeul, and Seliana, and the autochthonous lactic acid bacteria were isolated, identified, characterized and selected on the basis of the kinetics of acidification, the proteolytic activity, and the quotient of fermentation. Lactobacillus curvatus MA2, Pediococcus pentosaceus OA2, and Pediococcus acidilactici O1A1 were used together as mixed starter to obtain a selected sourdough. According to the backslopping procedure, a type I sourdough was made from a Tunisian flour (spontaneous sourdough). Compared to the use of the spontaneous sourdough, the one obtained with selected and mixed starters by a unique fermentation step, favored the increase of the concentrations of organic acids, phenols, and total free amino acids, the most suitable quotient of fermentation, and the most intense phytase and antioxidant activities, that increased ca. 20% compared to the control. Moreover, the selected starters improved the in vitro protein digestibility (ca. 82% when selected sourdough was used), textural and sensory features of the breads, as determined by textural profile analysis and panel test, respectively. This study aimed at exploiting the potential of selected autochthonous lactic acid bacteria and extending the use of a sourdough (type II), thanks to the set-up of a two-step fermentation protocol designed for application at the

  14. Yeast biodiversity in Slovenian wine regions: Case amino acids in spontaneous and induced fermentations of Malvasia

    Directory of Open Access Journals (Sweden)

    Raspor Peter I.

    2009-01-01

    Full Text Available Microbial biodiversity can also be reflected in final product composition. The work described in this paper investigates the differences in the amino acid composition of 14 Malvasia musts/wines fermented with local and commercial starter yeasts, comparing all to the spontaneous fermentations of must of the same origin. We tried to ascertain whether the changes were dependent upon different initiations of fermentations. A comparative study of free and total amino acid evolution was prepared. The total concentration of 15 amino acids studied was 1975 mg/l, and the concentration of fraee amino acids was 1061 mg/l. Spontaneous and induced fermentations showed different fermentation rates. Three to nine days were needed to reduce sugar by 50%. Although the proline is regarded as non-assailable amino acid, decreases in concentration were observed. Lysine was the only amino acid where the concentration increased. The minimal uptakes of amino acids occurred during spontaneous fermentations, whereas the maximal uptakes were observed in the fermentations inoculated with local starters.

  15. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    Directory of Open Access Journals (Sweden)

    Aleksandra Matuszyk

    2016-01-01

    Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  16. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.

    Science.gov (United States)

    Zong, Nan; Li, Fei; Deng, Yuanyuan; Shi, Jingshan; Jin, Feng; Gong, Qihai

    2016-10-15

    Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD. PMID:27368415

  17. Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity

    Institute of Scientific and Technical Information of China (English)

    Aimei Wang; Ning Hou; Dongyan Bao; Shuangyue Liu; Tao Xu

    2012-01-01

    In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. Alpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase.

  18. Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

    Directory of Open Access Journals (Sweden)

    Snehal S Patel

    2011-01-01

    Full Text Available Background: Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. Objective: This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Materials and Methods: Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.. Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o. for 8 weeks at the end of which blood samples were collected and analyzed for various biochemical parameters. Results: Injection of STZ produced significant loss of body weight (BW, polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypertension, bradycardia, and myocardial functional alterations. Treatment with gallic acid significantly lowered fasting glucose, the AUC glucose level in a dose-dependent manner; however, the insulin level was not increased significantly at same the dose and prevented loss of BW, polyphagia, and polydypsia in diabetic rats. It also prevented STZ-induced hyperlipidemia, hypertension, bradycardia, structural alterations in cardiac tissue such as increase in force of contraction, left ventricular weight to body weight ratio, collagen content, protein content, serum lactate dehydrogenase, and creatinine kinase levels in a dose-dependent manner. Further, treatment also produced reduction in lipid peroxidation and increase in antioxidant parameters in heart of diabetic rats. Conclusion: The results of this study suggest that gallic acid to be beneficial for the treatment of myocardial damage associated with type-1 diabetes.

  19. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    Science.gov (United States)

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  20. Complex Formation of Selected Radionuclides with Ligands Commonly Found in Ground Water: Low Molecular Organic Acids

    DEFF Research Database (Denmark)

    Jensen, Bror Skytte; Jensen, H.

    1985-01-01

    A general approach to the analysis of potentiometric data on complex formation between cations and polybasic amphoteric acids is described. The method is used for the characterisation of complex formation between Cs+, Sr2+, Co2+, La 3+, and Eu3+ with a α-hydroxy acids, tartaric acid and citric acid......, and with the α-amino acids, aspartic acid and L-cysteine. The cations have been chosen as typical components of reactor waste, and the acids because they are often found as products of microbial activity in pits or wherever organic material decays...

  1. Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method.

    Science.gov (United States)

    Lu, Chao; You, Jian-Xin; Liu, Hu-Chen; Li, Ping

    2016-01-01

    Health-care waste (HCW) management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM) issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi-granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS) for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS) can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively. PMID:27271652

  2. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site.

    Science.gov (United States)

    Rumpf, Tobias; Schiedel, Matthias; Karaman, Berin; Roessler, Claudia; North, Brian J; Lehotzky, Attila; Oláh, Judit; Ladwein, Kathrin I; Schmidtkunz, Karin; Gajer, Markus; Pannek, Martin; Steegborn, Clemens; Sinclair, David A; Gerhardt, Stefan; Ovádi, Judit; Schutkowski, Mike; Sippl, Wolfgang; Einsle, Oliver; Jung, Manfred

    2015-01-01

    Sirtuins are a highly conserved class of NAD(+)-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far. Here we present high-resolution structures of human Sirt2 in complex with highly selective drug-like inhibitors that show a unique inhibitory mechanism. Potency and the unprecedented Sirt2 selectivity are based on a ligand-induced structural rearrangement of the active site unveiling a yet-unexploited binding pocket. Application of the most potent Sirtuin-rearranging ligand, termed SirReal2, leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1, consistent with Sirt2 inhibition in vivo. Our structural insights into this unique mechanism of selective sirtuin inhibition provide the basis for further inhibitor development and selective tools for sirtuin biology. PMID:25672491

  3. Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method

    Science.gov (United States)

    Lu, Chao; You, Jian-Xin; Liu, Hu-Chen; Li, Ping

    2016-01-01

    Health-care waste (HCW) management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM) issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi-granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS) for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS) can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively. PMID:27271652

  4. Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method

    Directory of Open Access Journals (Sweden)

    Chao Lu

    2016-06-01

    Full Text Available Health-care waste (HCW management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi-granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively.

  5. Selective enrichment of sialic acid-containing glycopeptides using titanium dioxide chromatography with analysis by HILIC and mass spectrometry

    DEFF Research Database (Denmark)

    Palmisano, Giuseppe; Lendal, Sara Eun; Engholm-Keller, Kasper;

    2010-01-01

    -containing glycopeptides is achieved by using a low-pH buffer that contains a substituted acid such as glycolic acid to improve the binding efficiency and selectivity of SA-containing glycopeptides to the TiO(2) resin. By combining TiO(2) enrichment of sialylated glycopeptides with HILIC separation of deglycosylated......The terminal monosaccharide of cell surface glycoconjugates is typically a sialic acid (SA), and aberrant sialylation is involved in several diseases. Several methodological approaches in sample preparation and subsequent analysis using mass spectrometry (MS) have enabled the identification...

  6. Highly selective fluorogenic multianalyte biosensors constructed via enzyme-catalyzed coupling and aggregation-induced emission.

    Science.gov (United States)

    Wang, Xiaorui; Hu, Jinming; Zhang, Guoying; Liu, Shiyong

    2014-07-16

    The development of a highly selective and fast responsive fluorogenic biosensor for diverse analytes ranging from bioactive small molecules to specific antigens is highly desirable but remains a considerable challenge. We herein propose a new approach by integrating substrate-selective enzymatic reactions with fluorogens exhibiting aggregation-induced emission feature. Tyrosine-functionalized tetraphenylethene, TPE-Tyr, molecularly dissolves in aqueous media with negligible fluorescence emission; upon addition of horseradish peroxidase (HRP) and H2O2, effective cross-linking occurs due to HRP-catalyzed oxidative coupling of tyrosine moieties in TPE-Tyr. This leads to fluorescence emission turn-on and fast detection of H2O2 with high sensitivity and selectivity. As a validation of the new strategy's generality, we further configure it into the biosensor design for glucose through cascade enzymatic reactions and for pathologically relevant antigens (e.g., human carcinoembryonic antigen) by combining with the ELISA kit. PMID:24983204

  7. Selective Alignment of D2 Induced by Two Ultrashort Laser Pulses

    Institute of Scientific and Technical Information of China (English)

    Zeng-qiang Yang; Zhi-rong Guo; Gui-xian Ge

    2009-01-01

    The dynamics of molecular rotational wave packets of D2 induced by ultrashort laser pulses was investigated numerically by solving the time-dependent Schrodinger equation. Results show that an ultrashort pulse can manipulate a coherent rotational wave packet of D2 se-lectively. In the calculation, a first laser pulse was used to create a coherent rotational wave packet from an initial thermal ensemble of D2 at the temperature of 300 K. The second laser pulse was used to manipulate the rotational wave packet selectively around the first quarter and the three quarters revival. The alignment parameter and its Fourier transform amplitude both illustrate that the relative populations of even and odd rotational states in the final rotational wave packet of D2 can be manipulated by precisely selecting the time delay between the first and the second ultrashort pulse.

  8. Pressure-induced Phase Transition in Oleic Acid Studied by Raman Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    FAN Ya; ZHOU Jing; LI Shuang; GUAN Fu-Ying; XU Da-Peng

    2011-01-01

    High-pressure Raman studies up to 0.84 GPa are performed on oleic acid.Spectral analysis indicates that oleic acid undergoes a pressure-induced phase transition in the 0.29-0.36 GPa range.Only one high-pressure phase below 0.84 GPa is present,in which the polymethylene chains take the ordered all-trans conformation,with the methyl end of the chains exhibiting the ordered tt chain-end conformation and the olefin group taking the skewcis-skew' conformation.The conformational characters of the oleic acid molecule show that the high-pressure phase is the same as the low-temperature crystalline γ phase.The pressure-induced phase transition is typical of first-order transitions and the transition path during compression is different from that during cooling.Oleic acid (C1sH34O2) is one of the unsaturated fatty acids that appear naturally in a liquid state.It is one of the most common components of human diets,preventing coronary disease and breast cancer and benefiting people with diabetes.[1] A molecule of oleic acid possesses a carbon double bond,C =C,which leads to the occurrence of a phase transition when pressure is applied.[2] Therefore,the significance of high-pressure processing has recently increased as an alternative method of food preservation.So far some physical properties of oleic acid under pressures below 1 GPa have been investigated using a piston-cylinder device as a high-pressure apparatus.[2-10] However,no high-pressure Raman or any other in-situ experimental research on pressure-induced phase transition in oleic acid has been reported.In addition,the freezing point of oleic acid is 13.3℃,below which oleic acid crystallizes in three forms,namely,α,β and γ[11-17]%High-pressure Raman studies up to 0.84 Gpa are performed on oleic acid. Spectral analysis indicates that oleic acid undergoes a pressure-induced phase transition in the 0.29-0.36 Gpa range. Only one high-pressure phase below 0.84 Gpa is present, in which the polymethylene chains take the

  9. Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Nishi, Koji; Suzuki, Kenta; Sawamoto, Junpei; Tokizawa, Yuma; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko

    2016-09-01

    Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells. PMID:27630308

  10. Primary and secondary genetic responses after folic acid-induced acute renal injury in the mouse.

    Science.gov (United States)

    Calvet, J P; Chadwick, L J

    1994-12-01

    Folic acid-induced acute renal injury results in dramatic changes in gene expression. Among the genes affected by folic acid treatment are the primary response genes, c-fos and c-myc, which are thought to function to initiate cell cycle events. In this report, changes in the expression of three other genes in response to folic acid injury have been investigated: ornithine decarboxylase, epidermal growth factor (EGF), and sulfated glycoprotein-2 (SGP-2). Renal injury was found to cause a rapid decrease in EGF mRNA, which remained absent for several days after the initial injury, gradually returning to normal levels over an approximately 3-wk regeneration and recovery period. Ornithine decarboxylase mRNA showed a similar decrease. In contrast, folic acid caused a rapid increase in SGP-2 mRNA, which peaked several days after treatment, decreasing to normal levels over the 3-wk period. The mRNAs for the primary response genes were superinduced in the injured kidneys in the presence of the protein synthesis inhibitor cycloheximide. In contrast, the changes in EGF and SGP-2 mRNA levels were blocked by cycloheximide, indicating that these responses required new protein synthesis during the first few hours after folic acid injury. The opposite but parallel responses in the expression of the EGF and SGP-2 genes suggest that their regulation is coupled to the initial injury-induced dedifferentiation and subsequent return to the fully differentiated state.

  11. Polyunsaturated Fatty Acid Dietary Supplementation Induces Lipid Peroxidation in Normal Dogs

    Directory of Open Access Journals (Sweden)

    John M. Walters

    2010-01-01

    Full Text Available Polyunsaturated fatty acids (PUFAs have anti-inflammatory effects at low concentrations; however increased dietary consumption may conversely increase susceptibility to oxidation by free radicals. The objective of this study was to determine the effects of PUFAs on selective oxidative injury and inflammatory biomarkers in canine urine and serum. Dogs (n=54 consumed a diet supplemented with 0.5% conjugated linoleic acid/dry matter, 1.0% conjugated linoleic acid/dry matter, or 200 mg/kg docosahexaenoic acid/eicosapentaenoic acid for 21 days. All dogs exhibited significantly increased plasma PUFA concentrations. All dogs had significant elevations in urinary F2a isoprostane concentration, though dogs consuming a diet containing 1.0% conjugated linoleic acid/dry matter had the highest increase (P=.0052. Reduced glutathione concentrations within erythrocytes decreased significantly in all three dietary treatment groups (P=.0108. Treatment with diets containing 1.0% conjugated linoleic acid/dry matter resulted in the greatest increase in oxidant injury. Caution should be exercised when supplementing PUFAs as some types may increase oxidation.

  12. Selectivity of substrate binding and ionization of 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase.

    Science.gov (United States)

    Luanloet, Thikumporn; Sucharitakul, Jeerus; Chaiyen, Pimchai

    2015-08-01

    2-Methyl-3-hydroxypyridine-5-carboxylic acid (MHPC) oxygenase (EC 1.14.12.4) from Pseudomonas sp. MA-1 is a flavin-dependent monooxygenase that catalyzes a hydroxylation and aromatic ring cleavage reaction. The functional roles of two residues, Tyr223 and Tyr82, located ~ 5 Å away from MHPC, were characterized using site-directed mutagenesis, along with ligand binding, product analysis and transient kinetic experiments. Mutation of Tyr223 resulted in enzyme variants that were impaired in their hydroxylation activity and had Kd values for substrate binding 5-10-fold greater than the wild-type enzyme. Because this residue is adjacent to the water molecule that is located next to the 3-hydroxy group of MHPC, the results indicate that the interaction between Tyr223, H2 O and the 3-hydroxyl group of MHPC are important for substrate binding and hydroxylation. By contrast, the Kd for substrate binding of Tyr82His and Tyr82Phe variants were similar to that of the wild-type enzyme. However, only ~ 40-50% of the substrate was hydroxylated in the reactions of both variants, whereas most of the substrate was hydroxylated in the wild-type enzyme reaction. In free solution, MHPC or 5-hydroxynicotinic acid exists in a mixture of monoanionic and tripolar ionic forms, whereas only the tripolar ionic form binds to the wild-type enzyme. The binding of tripolar ionic MHPC would allow efficient hydroxylation through an electrophilic aromatic substitution mechanism. For the Tyr82His and Tyr82Phe variants, both forms of substrates can bind to the enzymes, indicating that the mutation at Tyr82 abolished the selectivity of the enzyme towards the tripolar ionic form. Transient kinetic studies indicated that the hydroxylation rate constants of both Tyr82 variants are approximately two- to 2.5-fold higher than that of the wild-type enzyme. Altogether, our findings suggest that Tyr82 is important for the binding selectivity of MHPC oxygenase towards the tripolar ionic species, whereas the

  13. A novel and selective oxidation of benzylic alcohols with polymer-supported periodic acid under mild aprotic conditions

    Institute of Scientific and Technical Information of China (English)

    Ali Reza Pourali; Mehrosadat Tabaean; S. Mohamad Reza Nazifi

    2012-01-01

    A new polymeric oxidizing reagent was prepared by supporting periodic acid on poly(1,4-phenylene-2,5-pyridine dicarboxyamide).This polymeric reagent was used for the selective oxidation of primary benzylic alcohols to the corresponding benzaldehydes in CH3CN at reflux conditions.Excellent selectivity was observed between primary benzyl alcohols and secondary ones as well as non-benzylic alcohols in the oxidation reactions.Allylic alcohols were also converted to the corresponding aldehydes with good yields.

  14. Activity, but not Expression, of Soluble and Cell Wall-Bound Acid Invertases Is Induced by Abscisic Acid in Developing Apple Fruit

    Institute of Scientific and Technical Information of China (English)

    Qiu-Hong Pan; Xiang-Chun Yu; Na Zhang; Xun Zou; Chang-Cao Peng; Xiu-Ling Wang; Ke-Qin Zou; Da-Peng Zhang

    2006-01-01

    The present experiment, involving both the in vivo injection of abscisic acid (ABA) into apple (Malus domestica Brohk.) fruits and the in vivo incubation of fruit tissues in ABA-containing medium, revealed that ABA activates both soluble and cell wall-bound acid invertases. Immunoblotting and enzyme-linked immunosorbent assays showed that this ABA-induced acid invertase activation is independent of the amount of enzyme present. The acid invertase activation induced by ABA is dependent on medium pH, time course, ABA dose, living tissue and developmental stage. Two isomers of cis-(+)-ABA, (-)-ABA and transABA, had no effect on acid invertases, showing that ABA-induced acid invertase activation is specific to physiologically active cis-(+)ABA. Protein kinase inhibitors K252a and H7 as well as acid phosphatase increased the ABA-induced effects. These data indicate that ABA specifically activates both soluble and cell wall-bound acid invertases by a posttranslational mechanism probably involving reversible protein phosphorylation, and this may be one of the mechanisms by which ABA is involved in regulating fruit development.

  15. Salt-inducible promoter derivable from a lactic acid bacterium, and its use in a lactic acid bacterium for production of a desired protein

    NARCIS (Netherlands)

    Sanders, Jan Willem; Kok, Jan; Venema, Gerard; Ledeboer, Adrianus Marinus

    1998-01-01

    The invention provides a salt-inducible promoter present in SEQ ID NO: 10 and derivable from a lactic acid bacterium in isolation from the coding sequence normally controlled by said promoter in a wild-type lactic acid bacterium, with modifications and important parts thereof. Also provided are a re

  16. Involvement of BID translocation in glycyrrhetinic acid and 11-deoxy glycyrrhetinic acid-induced attenuation of gastric cancer growth.

    Science.gov (United States)

    Lin, Dejian; Zhong, Wei; Li, Juan; Zhang, Bing; Song, Gang; Hu, Tianhui

    2014-01-01

    Glycyrrhetinic