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Sample records for alcohol oxidoreductases

  1. Enantiocomplementary Yarrowia lipolytica Oxidoreductases: Alcohol Dehydrogenase 2 and Short Chain Dehydrogenase/Reductase

    Directory of Open Access Journals (Sweden)

    Margit Winkler

    2013-08-01

    Full Text Available Enzymes of the non-conventional yeast Yarrowia lipolytica seem to be tailor-made for the conversion of lipophilic substrates. Herein, we cloned and overexpressed the Zn-dependent alcohol dehydrogenase ADH2 from Yarrowia lipolytica in Escherichia coli. The purified enzyme was characterized in vitro. The substrate scope for YlADH2 mediated oxidation and reduction was investigated spectrophotometrically and the enzyme showed a broader substrate range than its homolog from Saccharomyces cerevisiae. A preference for secondary compared to primary alcohols in oxidation direction was observed for YlADH2. 2-Octanone was investigated in reduction mode in detail. Remarkably, YlADH2 displays perfect (S-selectivity and together with a highly (R-selective short chain dehydrogenase/ reductase from Yarrowia lipolytica it is possible to access both enantiomers of 2-octanol in >99% ee with Yarrowia lipolytica oxidoreductases.

  2. Isolation and characterization of a Chinese hamster ovary cell line deficient in fatty alcohol:NAD+ oxidoreductase activity.

    OpenAIRE

    James, P F; Rizzo, W B; Lee, J.; Zoeller, R A

    1990-01-01

    We have isolated a mutant Chinese hamster ovary cell line that is defective in long-chain fatty alcohol oxidation. The ability of the mutant cells to convert labeled hexadecanol to the corresponding fatty acid in vivo was reduced to 5% of the parent strain. Whole-cell homogenates from the mutant strain, FAA.1, were deficient in long-chain fatty alcohol:NAD+ oxidoreductase (FAO; EC 1.1.1.192) activity, which catalyzes the oxidation of hexadecanol to hexadecanoic acid, although the intermediate...

  3. Sjögren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts.

    OpenAIRE

    Rizzo, W B; Craft, D A

    1991-01-01

    Sjögren-Larsson syndrome (SLS) is an inherited disorder associated with impaired fatty alcohol oxidation due to deficient activity of fatty alcohol:NAD+ oxidoreductase (FAO). FAO is a complex enzyme which consists of two separate proteins that sequentially catalyze the oxidation of fatty alcohol to fatty aldehyde and fatty acid. To determine which enzymatic component of FAO was deficient in SLS, we assayed fatty aldehyde dehydrogenase (FALDH) and fatty alcohol dehydrogenase in cultured fibrob...

  4. Regulation of enzyme activity of alcohol dehydrogenase through its interactions with pyruvate-ferredoxin oxidoreductase in Thermoanaerobacter tengcongensis.

    Science.gov (United States)

    Wang, Qian; Wang, Quanhui; Tong, Wei; Bai, Xue; Chen, Zhen; Zhao, Jingjing; Zhang, Jiyuan; Liu, Siqi

    2012-01-20

    Alcohol dehydrogenases (ADHs) from thermophilic microorganisms are interesting enzymes that have their potential applications in biotechnology and potentially provide insight into the mechanisms of action of thermo-tolerant proteins. The molecular mechanisms of ADHs under thermal stress in vivo have yet to be explored. Herein, we employed a proteomic strategy to survey the possible interactions of secondary-ADH (2-ADH) with other proteins in Thermoanaerobacter tengcongensis (T. tengcongensis) cultured at 75°C and found that 2-ADH, pyruvate-ferredoxin oxidoreductase (PFOR) and several glycolytic enzymes coexisted in a protein complex. Using anion exchange chromatography, the elution profile indicated that the native 2-ADH was present in two forms, PFOR-bound and PFOR-free. Immuno-precipitation and pull down analysis further validated the interactions between 2-ADH and PFOR. The kinetic behaviours of 2-ADH either in the recombinant or native form were evaluated with different substrates. The enzyme activity of 2-ADH was inhibited in a non-competitive mode by PFOR, implying the interaction of 2-ADH and PFOR negatively regulated alcohol formation. In T. tengcongensis, PFOR is an enzyme complex located at the upstream of 2-ADH in the alcohol generation pathway. These findings, therefore, offered a plausible mechanism for how alcohol metabolism is regulated by hetero-interactions between 2-ADH and PFOR, especially in anaerobic thermophiles. PMID:22222371

  5. The activity of some oxidoreductases in Hordeum vulgare L. plants treated with ethylmethanesulfonate and Rosmarinus officinalis L. hydro-alcoholic extracts

    OpenAIRE

    Gogu Gheorghita; Elena Ciornea; Ioana Daciana Mierlici

    2010-01-01

    This paper focuses on the activity of some oxidoreductases (catalase, peroxidase, superoxide- dismutase) in barley seedlings (Hordeum vulgare L.) after 6 hours of seeds treatment with different concentrations (0,01 – 0,50%) of ethyl-methane-sulfonate and 12 hours with hydro-alcoholic 0,5% rosemary (Rosmarinus officinalis L.) extract (EHR). The EMS treatments led to an obvious increase of the superoxide dismutase, catalase and peroxidase activity in plants, while the application of the hydro-a...

  6. The activity of some oxidoreductases in Hordeum vulgare L. plants treated with ethylmethanesulfonate and Rosmarinus officinalis L. hydro-alcoholic extracts

    Directory of Open Access Journals (Sweden)

    Gogu Gheorghita

    2011-02-01

    Full Text Available This paper focuses on the activity of some oxidoreductases (catalase, peroxidase, superoxide- dismutase in barley seedlings (Hordeum vulgare L. after 6 hours of seeds treatment with different concentrations (0,01 – 0,50% of ethyl-methane-sulfonate and 12 hours with hydro-alcoholic 0,5% rosemary (Rosmarinus officinalis L. extract (EHR. The EMS treatments led to an obvious increase of the superoxide dismutase, catalase and peroxidase activity in plants, while the application of the hydro-alcoholic rosemary extract, after the EMS treatment, led to a significant decrease of the activities of these enzymes, since the rosemary extract has an obvious antioxidant effect.

  7. Pyruvate:ferredoxin oxidoreductase and bifunctional aldehyde-alcohol dehydrogenase are essential for energy metabolism under oxidative stress in Entamoeba histolytica.

    Science.gov (United States)

    Pineda, Erika; Encalada, Rusely; Rodríguez-Zavala, José S; Olivos-García, Alfonso; Moreno-Sánchez, Rafael; Saavedra, Emma

    2010-08-01

    The in vitro Entamoeba histolytica pyruvate:ferredoxin oxidoreductase (EhPFOR) kinetic properties and the effect of oxidative stress on glycolytic pathway enzymes and fluxes in live trophozoites were evaluated. EhPFOR showed a strong preference for pyruvate as substrate over other oxoacids. The enzyme was irreversibly inactivated by a long period of saturating O(2) exposure (IC(50) 0.034 mm), whereas short-term exposure ( 90% inhibition allowed for partial restoration by addition of Fe(2+). CoA and acetyl-CoA prevented, whereas pyruvate exacerbated, inactivation induced by short-term saturating O(2) exposure. Superoxide dismutase was more effective than catalase in preventing the inactivation, indicating that reactive oxygen species (ROS) were involved. Hydrogen peroxide caused inactivation in an Fe(2+)-reversible fashion that was not prevented by the coenzymes, suggesting different mechanisms of enzyme inactivation by ROS. Structural analysis on an EhPFOR 3D model suggested that the protection against ROS provided by coenzymes could be attributable to their proximity to the Fe-S clusters. After O(2) exposure, live parasites displayed decreased enzyme activities only for PFOR (90%) and aldehyde dehydrogenase (ALDH; 68%) of the bifunctional aldehyde-alcohol dehydrogenase (EhADH2), whereas acetyl-CoA synthetase remained unchanged, explaining the increased acetate and lowered ethanol fluxes. Remarkably, PFOR and ALDH activities were restored after return of the parasites to normoxic conditions, which correlated with higher ethanol and lower acetate fluxes. These results identified amebal PFOR and ALDH of EhADH2 activities as markers of oxidative stress, and outlined their relevance as significant controlling steps of energy metabolism in parasites subjected to oxidative stress. PMID:20629749

  8. Sjögren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity.

    OpenAIRE

    Rizzo, W B; Dammann, A L; Craft, D A

    1988-01-01

    Lipid metabolism was studied in cultured skin fibroblasts from patients with the inherited disorder, Sjögren-Larsson syndrome (SLS). Intact SLS fibroblasts incubated in the presence of [1-14C]palmitate accumulated more radioactive hexadecanol than did normal cells, whereas incorporation of radioactivity into other cellular lipids was unaltered. The hexadecanol content of SLS fibroblasts was abnormally elevated. Hexadecanol accumulation was not due to increased fatty alcohol synthesis nor its ...

  9. Alcohol

    Science.gov (United States)

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  10. Alcohol

    NARCIS (Netherlands)

    Hendriks, H.F.; Tol, A. van

    2005-01-01

    Alcohol consumption affects overall mortality. Light to moderate alcohol consumption reduces the risk of coronary heart disease; epidemiological, physiological and genetic data show a causal relationship. Light to moderate drinking is also associated with a reduced risk of other vascular diseases an

  11. Alcohol

    Science.gov (United States)

    ... Date reviewed: January 2014 previous 1 • 2 For Teens For Kids For Parents MORE ON THIS TOPIC Word! Alcoholism What You Need to Know About Drugs What You Need to Know About Drugs: Depressants What Kids Say About: Drinking Alcohol Dealing With Peer Pressure Contact Us Print Resources Send to a friend ...

  12. Development of oxidoreductase based electrochemical biosensors

    OpenAIRE

    Rodrigues, Patrícia Raquel dos Santos

    2013-01-01

    Dissertação para obtenção do Grau de Mestre em Biotecnologia This thesis is divided in 2 sections, each describing the development of an oxidoreductase based biosensor. In the first part human Cytochrome P450 1A2 (CYP1A2) electrochemistry was studied, while the second is focused on the optimization of immobilization platforms and operation methods for amperometric biosensors, using cytochrome c nitrite reductase (ccNiR), (Desulfovibrio desulfuricans ATCC 27774) as a model enzyme. The...

  13. Cloning and expression of bacterial genes coding amino acid dehydrogenases (oxidoreductases)

    International Nuclear Information System (INIS)

    Full text: The synthesis of 15N-labeled amino acids from the corresponding α-ketoacids can be accomplished in vitro using bacterial NAD-dependent amino acid dehydrogenases. The example of alanine dehydrogenase (AlaDH) and leucine dehydrogenase (LeuDH) will be presented here. Both enzymes belong to NAD dependent oxidoreductase family. AlaDH or L-alanine NAD-oxidoreductase (EC 1.4.1.1) promotes the reversible oxidative deamination of L-alanine to pyruvate (pyruvic acid). LeuDH or L-leucine NAD-oxidoreductase (EC 1.4.1.9) catalyses the reversible oxidative deamination of many related L-amino acids to corresponding α-ketoacids. The bacterial genes encoding AlaDH from Bacillus subtilis and LeuDH from Bacillus stearothermophilus were cloned separately in pET21b vector, and overexpressed in Escherichia coli BL21(DE3) strain. The [15N]L-alanine was synthesized by reductive amination of pyruvate, in the presence of 15NH4Cl, NADH, AlaDH and glucose dehydrogenase. The [15N]L-leucine, [15N]L-isoleucine, [15N]L-norleucine, [15N]L-valine and [15N]L-norvaline were produced in the same conditions using LeuDH, as a catalyst, and α- ketoisocaproate, DL-α-keto-β-methyl-n-valerate, α-ketocaproate, α-ketoisovalerate and α-ketovalerate, respectively, as substrates. In all cases, the reaction mixtures included glucose dehydrogenase for NADH regeneration with glucose as electron donor. The NADH renewal is more convenient with glucose dehydrogenase than other methods described before using formate dehydrogenase or alcohol dehydrogenase. The glucose dehydrogenase is very active and do not inhibit 15N-labeled amino acid synthesis. As determined by mass spectroscopy, the 15N-labeled amino acids were synthesized with yields between 60% and 95%. Our results demonstrate the usefulness of recombinant amino acid dehydrogenases for in vitro synthesis of 15N-labeled amino acids. (author)

  14. A novel method for preparation of MNP@CS-tethered coenzyme for coupled oxidoreductase system.

    Science.gov (United States)

    Chen, Guo; Wu, Zhichao; Ma, Yunhui

    2015-02-20

    The immobilized cofactor NAD(H) is easily recovered from the reaction bulk, which is essential for repeated use of NAD(H) in the bioprocess catalyzed by NAD(H)-dependent oxidoreductase. Here, a magnetic nanoparticle platform was designed to immobilize both of the NADH and the NAD(+). The design was based on chitosan-coated magnetic nanoparticles (MNP@CS) which was activated by the EDC/NHS with the aid of azelaic acid as spacer. Interestingly, the succinimide group at the end of spacer arm catalyzed direct coupling of a carboxyl-terminal to the 6-amino group of the adenine residue of NAD(H). Our results indicated that 150 μmol NADH and 50 μmol NAD(+) was effectively attached to 1g MNP@CS at 25°C in 120 min and the prepared MNP@CS-NAD(H) showed good activity according to the coupling reaction of benzyl alcohol and acetaldehyde catalyzed by alcohol dehydrogenase. PMID:25617681

  15. NADPH Cytochrome P-450 Oxidoreductase and Susceptibility to Ketoconazole

    OpenAIRE

    Venkateswarlu, K; Kelly, Diane E.; Manning, Nigel J.; Kelly, Steven L.

    1998-01-01

    The phenotype of a strain of Saccharomyces cerevisiae containing a disruption of the gene encoding NADPH cytochrome P-450 oxidoreductase (CPR) was quantified biochemically and microbiologically, as were those of various transformants of this strain after expression of native CPR, cytochrome P-45051 (CYP51), and a fusion protein of CYP51-CPR (FUS). Only a 4-fold decrease in ergosterol biosynthesis was observed for the cpr strain, but ketoconazole sensitivity increased 200-fold, indicating hype...

  16. CRYSTAL STRUCTURE ANALYSIS OF A PUTATIVE OXIDOREDUCTASE FROM KLEBSIELLA PNEUMONIAE

    Energy Technology Data Exchange (ETDEWEB)

    Baig, M.; Brown, A.; Eswaramoorthy, S.; Swaminathan, S.

    2009-01-01

    Klebsiella pneumoniae, a gram-negative enteric bacterium, is found in nosocomial infections which are acquired during hospital stays for about 10% of hospital patients in the United States. The crystal structure of a putative oxidoreductase from K. pneumoniae has been determined. The structural information of this K. pneumoniae protein was used to understand its function. Crystals of the putative oxidoreductase enzyme were obtained by the sitting drop vapor diffusion method using Polyethylene glycol (PEG) 3350, Bis-Tris buffer, pH 5.5 as precipitant. These crystals were used to collect X-ray data at beam line X12C of the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL). The crystal structure was determined using the SHELX program and refi ned with CNS 1.1. This protein, which is involved in the catalysis of an oxidation-reduction (redox) reaction, has an alpha/beta structure. It utilizes nicotinamide adenine dinucleotide phosphate (NADP) or nicotine adenine dinucleotide (NAD) to perform its function. This structure could be used to determine the active and co-factor binding sites of the protein, information that could help pharmaceutical companies in drug design and in determining the protein’s relationship to disease treatment such as that for pneumonia and other related pathologies.

  17. Structure and function of Caulobacter crescentus aldose-aldose oxidoreductase.

    Science.gov (United States)

    Taberman, Helena; Andberg, Martina; Koivula, Anu; Hakulinen, Nina; Penttilä, Merja; Rouvinen, Juha; Parkkinen, Tarja

    2015-12-15

    Aldose-aldose oxidoreductase (Cc AAOR) is a recently characterized enzyme from the bacterial strain Caulobacter crescentus CB15 belonging to the glucose-fructose oxidoreductase/inositol dehydrogenase/rhizopine catabolism protein (Gfo/Idh/MocA) family. Cc AAOR catalyses the oxidation and reduction of a panel of aldose monosaccharides using a tightly bound NADP(H) cofactor that is regenerated in the catalytic cycle. Furthermore, Cc AAOR can also oxidize 1,4-linked oligosaccharides. In the present study, we present novel crystal structures of the dimeric Cc AAOR in complex with the cofactor and glycerol, D-xylose, D-glucose, maltotriose and D-sorbitol determined to resolutions of 2.0, 1.8, 1.7, 1.9 and 1.8 Å (1 Å=0.1 nm), respectively. These complex structures allowed for a detailed analysis of the ligand-binding interactions. The structures showed that the C1 carbon of a substrate, which is either reduced or oxidized, is close to the reactive C4 carbon of the nicotinamide ring of NADP(H). In addition, the O1 hydroxy group of the substrate, which is either protonated or deprotonated, is unexpectedly close to both Lys(104) and Tyr(189), which may both act as a proton donor or acceptor. This led us to hypothesize that this intriguing feature could be beneficial for Cc AAOR to catalyse the reduction of a linear form of a monosaccharide substrate and the oxidation of a pyranose form of the same substrate in a reaction cycle, during which the bound cofactor is regenerated.

  18. Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients.

    LENUS (Irish Health Repository)

    Sahakitrungruang, Taninee

    2009-12-01

    P450 oxidoreductase (POR) deficiency causes disordered steroidogenesis; severe mutations cause genital ambiguity in both sexes plus the Antley-Bixler skeletal malformation syndrome, whereas mild mutations can cause adult infertility.

  19. Genotype-Phenotype Analysis in Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency

    NARCIS (Netherlands)

    Krone, Nils; Reisch, Nicole; Idkowiak, Jan; Dhir, Vivek; Ivison, Hannah E.; Hughes, Beverly A.; Rose, Ian T.; O'Neil, Donna M.; Vijzelaar, Raymon; Smith, Matthew J.; MacDonald, Fiona; Cole, Trevor R.; Adolphs, Nicolai; Barton, John S.; Blair, Edward M.; Braddock, Stephen R.; Collins, Felicity; Cragun, Deborah L.; Dattani, Mehul T.; Day, Ruth; Dougan, Shelley; Feist, Miriam; Gottschalk, Michael E.; Gregory, John W.; Haim, Michaela; Harrison, Rachel; Olney, Ann Haskins; Hauffa, Berthold P.; Hindmarsh, Peter C.; Hopkin, Robert J.; Jira, Petr E.; Kempers, Marlies; Kerstens, Michiel N.; Khalifa, Mohamed M.; Koehler, Birgit; Maiter, Dominique; Nielsen, Shelly; O'Riordan, Stephen M.; Roth, Christian L.; Shane, Kate P.; Silink, Martin; Stikkelbroeck, Nike M. M. L.; Sweeney, Elizabeth; Szarras-Czapnik, Maria; Waterson, John R.; Williamson, Lori; Hartmann, Michaela F.; Taylor, Norman F.; Wudy, Stefan A.; Malunowicz, Ewa M.; Shackleton, Cedric H. L.; Arlt, Wiebke; Smith, M.J.

    2012-01-01

    Context: P450 oxidoreductase deficiency (PORD) is a unique congenital adrenal hyperplasia variant that manifests with glucocorticoid deficiency, disordered sex development (DSD), and skeletal malformations. No comprehensive data on genotype-phenotype correlations in Caucasian patients are available.

  20. Functional characterization of the chloroplast ferric chelate oxidoreductase enzyme.

    Science.gov (United States)

    Solti, Adám; Müller, Brigitta; Czech, Viktória; Sárvári, Éva; Fodor, Ferenc

    2014-05-01

    Iron (Fe) has an essential role in the biosynthesis of chlorophylls and redox cofactors, and thus chloroplast iron uptake is a process of special importance. The chloroplast ferric chelate oxidoreductase (cFRO) has a crucial role in this process but it is poorly characterized. To study the localization and mechanism of action of cFRO, sugar beet (Beta vulgaris cv Orbis) chloroplast envelope fractions were isolated by gradient ultracentrifugation, and their purity was tested by western blotting against different marker proteins. The ferric chelate reductase (FCR) activity of envelope fractions was studied in the presence of NAD(P)H (reductants) and FAD coenzymes. Reduction of Fe(III)-ethylenediaminetetraacetic acid was monitored spectrophotometrically by the Fe(II)-bathophenanthroline disulfonate complex formation. FCR activity, that is production of free Fe(II) for Fe uptake, showed biphasic saturation kinetics, and was clearly associated only to chloroplast inner envelope (cIE) vesicles. The reaction rate was > 2.5 times higher with NADPH than with NADH, which indicates the natural coenzyme preference of cFRO activity and its dependence on photosynthesis. FCR activity of cIE vesicles isolated from Fe-deficient plants also showed clear biphasic kinetics, where the KM of the low affinity component was elevated, and thus this component was down-regulated.

  1. Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects

    Directory of Open Access Journals (Sweden)

    Maria Giulia Battelli

    2016-01-01

    Full Text Available Xanthine oxidoreductase (XOR is the enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is widely distributed among species. In addition to this housekeeping function, mammalian XOR is a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various pathways. This review intends to address the physiological and pathological roles of XOR-derived oxidant molecules. The cytocidal action of XOR products has been claimed in relation to tissue damage, in particular damage induced by hypoxia and ischemia. Attempts to exploit this activity to eliminate unwanted cells via the construction of conjugates have also been reported. Moreover, different aspects of XOR activity related to phlogosis, endothelial activation, leukocyte activation, and vascular tone regulation, have been taken into consideration. Finally, the positive and negative outcomes concerning cancer pathology have been analyzed because XOR products may induce mutagenesis, cell proliferation, and tumor progression, but they are also associated with apoptosis and cell differentiation. In conclusion, XOR activity generates free radicals and other oxidant reactive species that may result in either harmful or beneficial outcomes.

  2. Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects.

    Science.gov (United States)

    Battelli, Maria Giulia; Polito, Letizia; Bortolotti, Massimo; Bolognesi, Andrea

    2016-01-01

    Xanthine oxidoreductase (XOR) is the enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is widely distributed among species. In addition to this housekeeping function, mammalian XOR is a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various pathways. This review intends to address the physiological and pathological roles of XOR-derived oxidant molecules. The cytocidal action of XOR products has been claimed in relation to tissue damage, in particular damage induced by hypoxia and ischemia. Attempts to exploit this activity to eliminate unwanted cells via the construction of conjugates have also been reported. Moreover, different aspects of XOR activity related to phlogosis, endothelial activation, leukocyte activation, and vascular tone regulation, have been taken into consideration. Finally, the positive and negative outcomes concerning cancer pathology have been analyzed because XOR products may induce mutagenesis, cell proliferation, and tumor progression, but they are also associated with apoptosis and cell differentiation. In conclusion, XOR activity generates free radicals and other oxidant reactive species that may result in either harmful or beneficial outcomes. PMID:26823950

  3. Characterization of apoptosis-related oxidoreductases from Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Patrícia Carneiro

    Full Text Available The genome from Neurospora crassa presented three open reading frames homologous to the genes coding for human AIF and AMID proteins, which are flavoproteins with oxidoreductase activities implicated in caspase-independent apoptosis. To investigate the role of these proteins, namely within the mitochondrial respiratory chain, we studied their cellular localization and characterized the respective null mutant strains. Efficiency of the respiratory chain was analyzed by oxygen consumption studies and supramolecular organization of the OXPHOS system was assessed through BN-PAGE analysis in the respective null mutant strains. The results demonstrate that, unlike in mammalian systems, disruption of AIF in Neurospora does not affect either complex I assembly or function. Furthermore, the mitochondrial respiratory chain complexes of the mutant strains display a similar supramolecular organization to that observed in the wild type strain. Further characterization revealed that N. crassa AIF appears localized to both the mitochondria and the cytoplasm, whereas AMID was found exclusively in the cytoplasm. AMID2 was detected in both mitochondria and cytoplasm of the amid mutant strain, but was barely discernible in wild type extracts, suggesting overlapping functions for the two proteins.

  4. Dual targeted poplar ferredoxin NADP(+) oxidoreductase interacts with hemoglobin 1.

    Science.gov (United States)

    Jokipii-Lukkari, Soile; Kastaniotis, Alexander J; Parkash, Vimal; Sundström, Robin; Leiva-Eriksson, Nélida; Nymalm, Yvonne; Blokhina, Olga; Kukkola, Eija; Fagerstedt, Kurt V; Salminen, Tiina A; Läärä, Esa; Bülow, Leif; Ohlmeier, Steffen; Hiltunen, J Kalervo; Kallio, Pauli T; Häggman, Hely

    2016-06-01

    Previous reports have connected non-symbiotic and truncated hemoglobins (Hbs) to metabolism of nitric oxide (NO), an important signalling molecule involved in wood formation. We have studied the capability of poplar (Populus tremula × tremuloides) Hbs PttHb1 and PttTrHb proteins alone or with a flavin-protein reductase to relieve NO cytotoxicity in living cells. Complementation tests in a Hb-deficient, NO-sensitive yeast (Saccharomyces cerevisiae) Δyhb1 mutant showed that neither PttHb1 nor PttTrHb alone protected cells against NO. To study the ability of Hbs to interact with a reductase, ferredoxin NADP(+) oxidoreductase PtthFNR was characterized by sequencing and proteomics. To date, by far the greatest number of the known dual-targeted plant proteins are directed to chloroplasts and mitochondria. We discovered a novel variant of hFNR that lacks the plastid presequence and resides in cytosol. The coexpression of PttHb1 and PtthFNR partially restored NO resistance of the yeast Δyhb1 mutant, whereas PttTrHb coexpressed with PtthFNR failed to rescue growth. YFP fusion proteins confirmed the interaction between PttHb1 and PtthFNR in plant cells. The structural modelling results indicate that PttHb1 and PtthFNR are able to interact as NO dioxygenase. This is the first report on dual targeting of central plant enzyme FNR to plastids and cytosol. PMID:27095407

  5. Alcoholism - resources

    Science.gov (United States)

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon/Alateen -- www.al-anon.org/home National Institute on Alcohol ...

  6. Alcohol Alert

    Science.gov (United States)

    ... Us You are here Home » Alcohol Alert Alcohol Alert The NIAAA Alcohol Alert is a quarterly bulletin that disseminates important research ... text. To order single copies of select Alcohol Alerts, see ordering Information . To view publications in PDF ...

  7. Alcohol Alert: Genetics of Alcoholism

    Science.gov (United States)

    ... and Reports » Alcohol Alert » Alcohol Alert Number 84 Alcohol Alert Number 84 Print Version The Genetics of ... immune defense system. Genes Encoding Enzymes Involved in Alcohol Breakdown Some of the first genes linked to ...

  8. Coordination environment of the active-site metal ion of liver alcohol dehydrogenase.

    OpenAIRE

    Makinen, M W; Yim, M B

    1981-01-01

    The coordination environment of the catalytically active metal ion of horse liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) has been investigated by electron paramagnetic resonance (EPR) methods with use of the active-site-specific Co2+-reconstituted enzyme. The EPR absorption spectrum of the metal-substituted enzyme is characteristic of a rhombically distorted environment. The spectrum of the enzyme--NAD+ complex shows approximate axial symmetry of the metal ion site, i...

  9. Combinatorial application of two aldehyde oxidoreductases on isobutanol production in the presence of furfural.

    Science.gov (United States)

    Seo, Hyung-Min; Jeon, Jong-Min; Lee, Ju Hee; Song, Hun-Suk; Joo, Han-Byul; Park, Sung-Hee; Choi, Kwon-Young; Kim, Yong Hyun; Park, Kyungmoon; Ahn, Jungoh; Lee, Hongweon; Yang, Yung-Hun

    2016-01-01

    Furfural is a toxic by-product formulated from pretreatment processes of lignocellulosic biomass. In order to utilize the lignocellulosic biomass on isobutanol production, inhibitory effect of the furfural on isobutanol production was investigated and combinatorial application of two oxidoreductases, FucO and YqhD, was suggested as an alternative strategy. Furfural decreased cell growth and isobutanol production when only YqhD or FucO was employed as an isobutyraldehyde oxidoreductase. However, combinatorial overexpression of FucO and YqhD could overcome the inhibitory effect of furfural giving higher isobutanol production by 110% compared with overexpression of YqhD. The combinatorial oxidoreductases increased furfural detoxification rate 2.1-fold and also accelerated glucose consumption 1.4-fold. When it compares to another known system increasing furfural tolerance, membrane-bound transhydrogenase (pntAB), the combinatorial aldehyde oxidoreductases were better on cell growth and production. Thus, to control oxidoreductases is important to produce isobutanol using furfural-containing biomass and the combinatorial overexpression of FucO and YqhD can be an alternative strategy. PMID:26660478

  10. Combinatorial application of two aldehyde oxidoreductases on isobutanol production in the presence of furfural.

    Science.gov (United States)

    Seo, Hyung-Min; Jeon, Jong-Min; Lee, Ju Hee; Song, Hun-Suk; Joo, Han-Byul; Park, Sung-Hee; Choi, Kwon-Young; Kim, Yong Hyun; Park, Kyungmoon; Ahn, Jungoh; Lee, Hongweon; Yang, Yung-Hun

    2016-01-01

    Furfural is a toxic by-product formulated from pretreatment processes of lignocellulosic biomass. In order to utilize the lignocellulosic biomass on isobutanol production, inhibitory effect of the furfural on isobutanol production was investigated and combinatorial application of two oxidoreductases, FucO and YqhD, was suggested as an alternative strategy. Furfural decreased cell growth and isobutanol production when only YqhD or FucO was employed as an isobutyraldehyde oxidoreductase. However, combinatorial overexpression of FucO and YqhD could overcome the inhibitory effect of furfural giving higher isobutanol production by 110% compared with overexpression of YqhD. The combinatorial oxidoreductases increased furfural detoxification rate 2.1-fold and also accelerated glucose consumption 1.4-fold. When it compares to another known system increasing furfural tolerance, membrane-bound transhydrogenase (pntAB), the combinatorial aldehyde oxidoreductases were better on cell growth and production. Thus, to control oxidoreductases is important to produce isobutanol using furfural-containing biomass and the combinatorial overexpression of FucO and YqhD can be an alternative strategy.

  11. Directed Molecular Evolution of Nitrite Oxido-reductase by DNA-shuffling

    Institute of Scientific and Technical Information of China (English)

    JUN-WEN LI; JIN-LAI ZHENG; XIN-WEI WANG; MIN JIN; FU-HUAN CHAO

    2007-01-01

    Objective To develtop directly molecular evolution of nitrite oxido-reductase using DNA-shuffling technique because nitrobacteria grow extremely slow and are unable to nitrify effectively inorganic nitrogen in wastewater treatment. Methods The norB gene coding the nitrite oxido-reductase in nitrobacteria was cloned and sequenced. Then, directed molecular evolution of nitrite oxido-reductase was developed by DNA-shuffling of 15 norB genes from different nitrobacteria. Results After DNA-shuffling with sexual PCR and staggered extension process PCR, the sequence was different from its parental DNA fragments and the homology ranged from 98% to 99%. The maximum nitrification rate of the modified bacterium of X16 by modified bacterium had the same characteristics of its parental bacteria of E. coli and could grow rapidly in normal cultures.Conclusion DNA-shuffling was successfully used to engineer E. coli, which had norB gene and could degrade inorganic nitrogen effectively.

  12. Alcoholism and Alcohol Abuse

    Science.gov (United States)

    ... cancers. It can cause damage to the liver, brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the risk of death from car crashes, injuries, homicide, and suicide. If you want to stop ...

  13. 40 CFR 174.524 - Glyphosate Oxidoreductase GOX or GOXv247 in all plants; exemption from the requirement of a...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Glyphosate Oxidoreductase GOX or... REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Tolerances and Tolerance Exemptions § 174.524 Glyphosate... Glyphosate Oxidoreductase GOX or GOXv247 enzyme in all plants are exempt from the requirement of a...

  14. Single molecule activity measurements of cytochrome P450 oxidoreductase reveal the existence of two discrete functional states

    DEFF Research Database (Denmark)

    Laursen, Tomas; Singha, Aparajita; Rantzau, Nicolai;

    2014-01-01

    Electron transfer between membrane spanning oxi-doreductase enzymes crucially controls vital meta-bolic processes. Here we studied for the first time with single molecule resolution the function of P450 oxidoreductase (POR), the canonical membrane spanning activator of all microsomal cytochrome P...

  15. Molecular and biochemical characterization of bifunctional pyruvate decarboxylases and pyruvate ferredoxin oxidoreductases from Thermotoga maritima and Thermotoga hypogea.

    Science.gov (United States)

    Eram, Mohammad S; Wong, Alton; Oduaran, Erica; Ma, Kesen

    2015-12-01

    Hyperthermophilic bacteria Thermotoga maritima and Thermotoga hypogea produce ethanol as a metabolic end product, which is resulted from acetaldehyde reduction catalysed by an alcohol dehydrogenase (ADH). However, the enzyme that is involved in the production of acetaldehyde from pyruvate is not well characterized. An oxygen sensitive and coenzyme A-dependent pyruvate decarboxylase (PDC) activity was found to be present in cell free extracts of T. maritima and T. hypogea. Both enzymes were purified and found to have pyruvate ferredoxin oxidoreductase (POR) activity, indicating their bifunctionality. Both PDC and POR activities from each of the purified enzymes were characterized in regards to their optimal assay conditions including pH dependency, oxygen sensitivity, thermal stability, temperature dependency and kinetic parameters. The close relatedness of the PORs that was shown by sequence analysis could be an indication of the presence of such bifunctionality in other hyperthermophilic bacteria. This is the first report of a bifunctional PDC/POR enzyme in hyperthermophilic bacteria. The PDC and the previously reported ADHs are most likely the key enzymes catalysing the production of ethanol from pyruvate in bacterial hyperthermophiles.

  16. Structural determinants of stereospecificity in yeast alcohol dehydrogenase.

    OpenAIRE

    Weinhold, E G; Glasfeld, A; Ellington, A D; Benner, S A

    1991-01-01

    Replacing Leu-182 by Ala in yeast alcohol dehydrogenase (YADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) yields a mutant that retains 34% of its kcat value and makes one stereochemical "mistake" every 850,000 turnovers (instead of approximately 1 error every 7,000,000,000 turnovers in native YADH) in its selection of the 4-Re hydrogen of NADH. Half of the decrease in stereochemical fidelity comes from an increase in the rate of transfer of the 4-Si hydrogen of NADH. The mutant also accepts 5-m...

  17. Myths about drinking alcohol

    Science.gov (United States)

    ... to. I spend a lot of time getting alcohol, drinking alcohol, or recovering from the effects of alcohol. ... Institute on Alcohol Abuse and Alcoholism. Overview of Alcohol Consumption. www.niaaa.nih.gov/alcohol-health/overview-alcohol- ...

  18. Endoplasmic reticulum (ER Chaperones and Oxidoreductases: Critical Regulators of Tumor Cell Survival and Immunorecognition

    Directory of Open Access Journals (Sweden)

    Thomas eSimmen

    2014-10-01

    Full Text Available Endoplasmic reticulum (ER chaperones and oxidoreductases are abundant enzymes that mediate the production of fully folded secretory and transmembrane proteins. Resisting the Golgi and plasma membrane-directed bulk flow, ER chaperones and oxidoreductases enter retrograde trafficking whenever they are pulled outside of the ER. However, solid tumors are characterized by the increased production of reactive oxygen species (ROS, combined with reduced blood flow that leads to low oxygen supply and ER stress. Under these conditions, hypoxia and the unfolded protein response (UPR upregulate ER chaperones and oxidoreductases. When this occurs, ER oxidoreductases and chaperones become important regulators of tumor growth. However, under these conditions, these proteins not only promote the production of proteins, but also alter the properties of the plasma membrane and hence modulate tumor immune recognition. For instance, high levels of calreticulin serve as an eat-me signal on the surface of tumor cells. Conversely, both intracellular and surface BiP/GRP78 promotes tumor growth. Other ER folding assistants able to modulate the properties of tumor tissue include protein disulfide isomerase (PDI, Ero1α and GRP94. Understanding the roles and mechanisms of ER chaperones in regulating tumor cell functions and immunorecognition will lead to important insight for the development of novel cancer therapies.

  19. An investigation on the quinoprotein nature of some fungal and plant oxidoreductases

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Maccarrone, M.; Veldink, G.A.

    1991-01-01

    The presence of pyrroloquinoline quinone (PQQ) as the organic cofactor of Dactylium dendroides galactose oxidase and lentil (Lens culinaris) seedling amine oxidase, purported PQQ-containing oxidoreductases (Van der Meer, R. A., Jongejan, J. A., and Duine, J. A. (1989) J. Biol. Chem. 264, 7792-7794;

  20. Evolution of NADPH-cytochrome P450 oxidoreductases (POR) in Apiales - POR 1 is missing

    DEFF Research Database (Denmark)

    Andersen, Trine Bundgaard; Hansen, Niels Bjørn; Laursen, Tomas;

    2016-01-01

    The NADPH-dependent cytochrome P450 oxidoreductase (POR) is the obligate electron donor to eukaryotic microsomal cytochromes P450 enzymes. The number of PORs within plant species is limited to one to four isoforms, with the most common being two PORs per plant. These enzymes provide electrons to ...

  1. On the purification and preliminary crystallographic analysis of isoquinoline 1-oxidoreductase from Brevundimonas diminuta 7

    OpenAIRE

    Boer, D. Roeland; Müller, Axel; Fetzner, Susanne; Lowe, David J.; Romão, Maria João

    2004-01-01

    Crystallization of isoquinoline 1-oxidoreductase from B. diminuta was achieved using two different crystallization buffers. Streak-seeding and cross-linking were essential to obtain well diffracting crystals. Suitable cryo-conditions were found and a structure solution was obtained by molecular replacement.

  2. Molecular Cloning and Characterization of a Broad Substrate Terpenoid Oxidoreductase from Artemisia annua

    NARCIS (Netherlands)

    Ryden, Anna-Margareta; Ruyter-Spira, Carolien; Litjens, Ralph; Takahashi, Shunji; Quax, Wim; Osada, Hiroyuki; Bouwmeester, Harro; Kayser, Oliver

    2010-01-01

    From Artemisia annua L., a new oxidoreductase (Red 1) was cloned, sequenced and functionally characterized. Through bioinformatics, heterologous protein expression and enzyme substrate conversion assays, the elucidation of the enzymatic capacities of Red1 was achieved. Red1 acts on monoterpenoids, a

  3. Molecular cloning and characterization of a broad substrate terpenoid oxidoreductase from Artemisia annua.

    NARCIS (Netherlands)

    Ryden, A.M.; Ruyter-Spira, C.P.; Litjens, R.; Takahashi, S.; Quax, W.J.; Osada, H.; Bouwmeester, H.J.; Kayser, O.

    2010-01-01

    From Artemisia annua L., a new oxidoreductase (Red 1) was cloned, sequenced and functionally characterized. Through bioinformatics, heterologous protein expression, and enzyme substrate conversion assays, the elucidation of the enzymatic capacities of Red1 was achieved. Red1 acts on monoterpenoids,

  4. National Institute on Alcohol Abuse and Alcoholism

    Science.gov (United States)

    Skip to main content National Institute on Alcohol Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use ...

  5. Characterization of a new aryl-alcohol oxidase secreted by the phytopathogenic fungus Ustilago maydis.

    Science.gov (United States)

    Couturier, Marie; Mathieu, Yann; Li, Ai; Navarro, David; Drula, Elodie; Haon, Mireille; Grisel, Sacha; Ludwig, Roland; Berrin, Jean-Guy

    2016-01-01

    The discovery of novel fungal lignocellulolytic enzymes is essential to improve the breakdown of plant biomass for the production of second-generation biofuels or biobased materials in green biorefineries. We previously reported that Ustilago maydis grown on maize secreted a diverse set of lignocellulose-acting enzymes including hemicellulases and putative oxidoreductases. One of the most abundant proteins of the secretome was a putative glucose-methanol-choline (GMC) oxidoreductase. The phylogenetic prediction of its function was hampered by the few characterized members within its clade. Therefore, we cloned the gene and produced the recombinant protein to high yield in Pichia pastoris. Functional screening using a library of substrates revealed that this enzyme was able to oxidize several aromatic alcohols. Of the tested aryl-alcohols, the highest oxidation rate was obtained with 4-anisyl alcohol. Oxygen, 1,4-benzoquinone, and 2,6-dichloroindophenol can serve as electron acceptors. This GMC oxidoreductase displays the characteristics of an aryl-alcohol oxidase (E.C.1.1.3.7), which is suggested to act on the lignin fraction in biomass.

  6. Lactic acid-producing yeast cells having nonfunctional L- or D-lactate:ferricytochrome C oxidoreductase cells

    Science.gov (United States)

    Miller, Matthew; Suominen, Pirkko; Aristidou, Aristos; Hause, Benjamin Matthew; Van Hoek, Pim; Dundon, Catherine Asleson

    2012-03-20

    Yeast cells having an exogenous lactate dehydrogenase gene ae modified by reducing L- or D-lactate:ferricytochrome c oxidoreductase activity in the cell. This leads to reduced consumption of lactate by the cell and can increase overall lactate yields in a fermentation process. Cells having the reduced L- or D-lactate:ferricytochrome c oxidoreductase activity can be screened for by resistance to organic acids such as lactic or glycolic acid.

  7. Optimizing Cofactor Specificity of Oxidoreductase Enzymes for the Generation of Microbial Production Strains—OptSwap

    DEFF Research Database (Denmark)

    King, Zachary A.; Feist, Adam

    2013-01-01

    specificities of oxidoreductase enzyme and complementary reaction knockouts. Using the Escherichia coli genome-scale metabolic model iJO1366, OptSwap predicted eight growth-coupled production designs with significantly greater product yields or substrate-specific productivities than designs predicted with gene...... knockouts alone. These designs were identified for the production of L-alanine, succinate, acetate, and D-lactate under modeled conditions. Simulations predicted that production of L-alanine and D-lactate can be strongly coupled to growth by knocking out three reactions and swapping the cofactor specificity...... designs predicted solely with reaction knockouts. The OptSwap formulation can be readily extended to additional organisms, and the constraints enforcing oxidoreductase specificity swaps can be extended to target other specificity sets of interest....

  8. Correlation of Cytochrome P450 Oxidoreductase Expression with the Expression of 10 Isoforms of Cytochrome P450 in Human Liver

    Science.gov (United States)

    Zhang, Hai-Feng; Li, Zhi-Hui; Liu, Jia-Yu; Liu, Ting-Ting; Wang, Ping; Fang, Yan; Zhou, Jun; Cui, Ming-Zhu; Gao, Na; Tian, Xin; Gao, Jie; Wen, Qiang; Jia, Lin-Jing

    2016-01-01

    Human cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (P450s) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 12.8-fold, from 12.59 to 160.97 pmol/mg, with a median value of 67.99 pmol/mg; POR mRNA expression varied by 26.4-fold. POR activity was less variable with a median value of 56.05 nmol/min per milligram. Cigarette smoking and alcohol consumption clearly influenced POR activity. Liver samples with a 2286822 TT genotype had significantly higher POR mRNA expression than samples with CT genotype. Homozygous carriers of POR2286822C>T, 2286823G>A, and 3823884A>C had significantly lower POR protein levels compared with the corresponding heterozygous carriers. Liver samples from individuals homozygous at 286823G>A, 1135612A>G, and 10954732G>A generally had lower POR activity levels than those from heterozygous or wild-type samples, whereas the common variant POR*28 significantly increased POR activity. There was a strong association between POR and the expression of P450 isoforms at the mRNA and protein level, whereas the relationship at the activity level, as well as the effect of POR protein content on P450 activity, was less pronounced. POR transcription was strongly correlated with both hepatocyte nuclear factor 4 alpha and pregnane X receptor mRNA levels. In conclusion, we have elucidated some potentially important correlations between POR single-nucleotide polymorphisms and POR expression in the Chinese population and have developed a database that correlates POR expression with the expression and activity of 10 P450s important in drug metabolism. PMID:27271371

  9. Correlation of Cytochrome P450 Oxidoreductase Expression with the Expression of 10 Isoforms of Cytochrome P450 in Human Liver.

    Science.gov (United States)

    Zhang, Hai-Feng; Li, Zhi-Hui; Liu, Jia-Yu; Liu, Ting-Ting; Wang, Ping; Fang, Yan; Zhou, Jun; Cui, Ming-Zhu; Gao, Na; Tian, Xin; Gao, Jie; Wen, Qiang; Jia, Lin-Jing; Qiao, Hai-Ling

    2016-08-01

    Human cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (P450s) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 12.8-fold, from 12.59 to 160.97 pmol/mg, with a median value of 67.99 pmol/mg; POR mRNA expression varied by 26.4-fold. POR activity was less variable with a median value of 56.05 nmol/min per milligram. Cigarette smoking and alcohol consumption clearly influenced POR activity. Liver samples with a 2286822 TT genotype had significantly higher POR mRNA expression than samples with CT genotype. Homozygous carriers of POR2286822C>T, 2286823G>A, and 3823884A>C had significantly lower POR protein levels compared with the corresponding heterozygous carriers. Liver samples from individuals homozygous at 286823G>A, 1135612A>G, and 10954732G>A generally had lower POR activity levels than those from heterozygous or wild-type samples, whereas the common variant POR*28 significantly increased POR activity. There was a strong association between POR and the expression of P450 isoforms at the mRNA and protein level, whereas the relationship at the activity level, as well as the effect of POR protein content on P450 activity, was less pronounced. POR transcription was strongly correlated with both hepatocyte nuclear factor 4 alpha and pregnane X receptor mRNA levels. In conclusion, we have elucidated some potentially important correlations between POR single-nucleotide polymorphisms and POR expression in the Chinese population and have developed a database that correlates POR expression with the expression and activity of 10 P450s important in drug metabolism. PMID:27271371

  10. Alcohol Test

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The recent alcohol tax increase poses a challenge to China’s white spirits makers Alcohol, rather than wine, is an in-dispensable component to Chinese table culture. The financial crisis has failed to affect white spirits sales, but an alcohol tax increase might.

  11. Xanthine oxidoreductase in cancer: more than a differentiation marker.

    Science.gov (United States)

    Battelli, Maria Giulia; Polito, Letizia; Bortolotti, Massimo; Bolognesi, Andrea

    2016-03-01

    Human xanthine oxidoreductase (XOR) catalyzes the last two steps of purine catabolism and is present in two interconvertible forms, which may utilize O2 or NAD(+) as electron acceptors. In addition to uric acid, XOR products may comprise reactive oxygen and nitrogen species that have many biologic effects, including inflammation, endothelial dysfunction, and cytotoxicity, as well as mutagenesis and induction of proliferation. XOR is strictly modulated at the transcriptional and post-translational levels, and its expression and activity are highly variable in cancer. Xanthine oxidoreductase (XOR) expression has been negatively associated with a high malignity grade and a worse prognosis in neoplasms of the breast, liver, gastrointestinal tract, and kidney, which normally express a high level of XOR protein. However, the level of XOR expression may be associated with a worse outcome in cancer of low XOR-expressing cells, in relation to the inflammatory response elicited through the tissue damage induced by tumor growth. Xanthine oxidoreductase (XOR) has been implicated in the process of oncogenesis either directly because it is able to catalyze the metabolic activation of carcinogenic substances or indirectly through the action of XOR-derived reactive oxygen and nitrogen species. The role of uric acid is characterized by both oxidant and antioxidant action; thus, it is still debatable whether control of uricemia may be helpful to improve the outcomes of tumor illness. PMID:26687331

  12. Alcoholic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Gonzalo; Guzzo-Merello; Marta; Cobo-Marcos; Maria; Gallego-Delgado; Pablo; Garcia-Pavia

    2014-01-01

    Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy(ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM.

  13. Differences in the secretion pattern of oxidoreductases from Bjerkandera adusta induced by a phenolic olive mill extract.

    Science.gov (United States)

    Reina, Rocío; Kellner, Harald; Jehmlich, Nico; Ullrich, René; García-Romera, Inmaculada; Aranda, Elisabet; Liers, Christiane

    2014-11-01

    The secretome of the white-rot fungus Bjerkandera adusta produced in synthetic Kirk medium was compared to that supplemented with an aqueous phenol-rich extract of dry olive mill residues (ADOR). Distinct changes in the protein composition of oxidoreductases, namely diverse class-II peroxidases and aryl alcohol oxidases were found. In the ADOR-supplemented medium (ASC), 157 distinct proteins were identified by the secretome analysis, whereas only 59 of them were identified without ADOR supplementation (Kirk medium culture; KM). Proteome analysis indicated that the number of peroxidases produced in ASC was more than doubled (from 4 to 11) compared to KM. Two short manganese peroxidases (MnP1 and MnP6) and one versatile peroxidase (VP1) represented 29% of the relative abundance (NSAF) in ASC. Two of them (MnP1 and VP1) were also detected in KM at a relative abundance (NSAF) of only 3%. Further peroxidases present in ASC were one lignin peroxidase (LiP2), one generic peroxidase (GP) and three dye-decolorizing peroxidases (DyPs). The relative abundance of DyPs and aryl alcohol oxidases (AAO) were lower in ASC in comparison to KM. In addition to peptide sequence analysis, the secretion of Mn(2+)-oxidizing peroxidases as well as AAOs were followed by enzyme measurement. The Mn(2+)-oxidizing activity increased nearly 30-fold (from 10 to 281Ul(-1)) after ADOR addition. Two enzymes responsible for that activity were successfully purified (BadVPI and BadVPII). To prove a potential involvement of these enzymes in the degradation of aromatic compounds, BadVPI was tested for its ability to degrade the recalcitrant dehydrogenated polymer (DHP, synthetic lignin). These results show that natural phenol-rich materials act as secretome-stimulating additives. Applying these substances enables us to investigate fungal degradation and detoxification processes and gives more insight into the complexity of fungal secretomes, e.g. of white-rot fungi. PMID:25069088

  14. Purification, characterization, and properties of an aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646.

    OpenAIRE

    Li, T.; Rosazza, J P

    1997-01-01

    An aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646 was purified 196-fold by a combination of Mono-Q, Reactive Green 19 agarose affinity, and hydroxyapatite chromatographies. The purified enzyme runs as a single band of 140 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular mass was estimated to be 163 +/- 3.8 kDa by gel filtration, indicating that this enzyme is a monomeric protein. The binding of the enzyme to Reactive Green 19 agarose was Mg2+ de...

  15. Differentially regulated NADPH:cytochrome P450 oxidoreductases in parsley

    OpenAIRE

    Koopmann, Edda; Hahlbrock, Klaus

    1997-01-01

    Two NADPH:cytochrome P450 oxidoreductases (CPRs) from parsley (Petroselinum crispum) were cloned, and the complete proteins were expressed and functionally identified in yeast. The two enzymes, designated CPR1 and CPR2, are 80% identical in amino acid sequence with one another and about 75% identical with CPRs from several other plant species. The mRNA accumulation patterns for CPR1 and CPR2 in fungal elicitor-treated or UV-irradiated cultured parsley cells and in developing or infected parsl...

  16. Neutral metal-bound water is the base catalyst in liver alcohol dehydrogenase.

    OpenAIRE

    Makinen, M W; Maret, W.; Yim, M B

    1983-01-01

    The catalytic role of the active site metal-water complex in horse liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) is investigated on the basis of a comparative analysis of the pH dependence of steady-state kinetic parameters of the native and active-site-specific Co2+-reconstituted enzyme and on the basis of assignment of the coordination environment of the Co2+ by electron paramagnetic resonance methods. The pH dependence of the kinetic parameters for the oxidation of ...

  17. Alcohol Energy Drinks

    Science.gov (United States)

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 17728 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

  18. Alcohol during Pregnancy

    Science.gov (United States)

    ... Home > Pregnancy > Is it safe? > Alcohol during pregnancy Alcohol during pregnancy E-mail to a friend Please ... and fetal alcohol spectrum disorders. How does drinking alcohol during pregnancy affect your baby's health? Drinking alcohol ...

  19. Alcohol and pregnancy

    Science.gov (United States)

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... lead to lifelong damage. DANGERS OF ALCOHOL DURING PREGNANCY Drinking a lot of alcohol during pregnancy can ...

  20. Crystal structures of Pseudomonas syringae pv. tomato DC3000 quinone oxidoreductase and its complex with NADPH

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Xiaowei [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Hongmei; Gao, Yu; Li, Mei [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China); Chang, Wenrui, E-mail: wrchang@sun5.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China)

    2009-12-18

    Zeta-crystallin-like quinone oxidoreductase is NAD(P)H-dependent and catalyzes one-electron reduction of certain quinones to generate semiquinone. Here we present the crystal structures of zeta-crystallin-like quinone oxidoreductase from Pseudomonas syringae pv. tomato DC3000 (PtoQOR) and its complexes with NADPH determined at 2.4 and 2.01 A resolutions, respectively. PtoQOR forms as a homologous dimer, each monomer containing two domains. In the structure of the PtoQOR-NADPH complex, NADPH locates in the groove between the two domains. NADPH binding causes obvious conformational changes in the structure of PtoQOR. The putative substrate-binding site of PtoQOR is wider than that of Escherichia coli and Thermus thermophilus HB8. Activity assays show that PtoQOR has weak 1,4-benzoquinone catalytic activity, and very strong reduction activity towards large substrates such as 9,10-phenanthrenequinone. We propose a model to explain the conformational changes which take place during reduction reactions catalyzed by PtoQOR.

  1. On the purification and preliminary crystallographic analysis of isoquinoline 1-oxidoreductase from Brevundimonas diminuta 7

    Energy Technology Data Exchange (ETDEWEB)

    Boer, D. Roeland; Müller, Axel [REQUIMTE/CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Fetzner, Susanne [Westfälische Wilhelms-Universität Münster, Institut für Molekulare Mikrobiologie und Biotechnologie, Corrensstrasse 3, D-48149 Münster (Germany); Lowe, David J. [Biological Chemistry Department, John Innes Centre, Colney, Norwich NR4 7UH (United Kingdom); Romão, Maria João, E-mail: mromao@dq.fct.unl.pt [REQUIMTE/CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2005-01-01

    Crystallization of isoquinoline 1-oxidoreductase from B. diminuta was achieved using two different crystallization buffers. Streak-seeding and cross-linking were essential to obtain well diffracting crystals. Suitable cryo-conditions were found and a structure solution was obtained by molecular replacement. Isoquinoline 1-oxidoreductase (IOR) from Brevundimonas diminuta is a mononuclear molybdoenzyme of the xanthine-dehydrogenase family of proteins and catalyzes the conversion of isoquinoline to isoquinoline-1-one. Its primary sequence and behaviour, specifically in its substrate specificity and lipophilicity, differ from other members of the family. A crystal structure of the enzyme is expected to provide an explanation for these differences. This paper describes the crystallization and preliminary X-ray diffraction experiments as well as an optimized purification protocol for IOR. Crystallization of IOR was achieved using two different crystallization buffers. Streak-seeding and cross-linking were essential to obtain well diffracting crystals. Suitable cryo-conditions were found and a structure solution was obtained by molecular replacement. However, phases need to be improved in order to obtain a more interpretable electron-density map.

  2. Crystal structures of Pseudomonas syringae pv. tomato DC3000 quinone oxidoreductase and its complex with NADPH

    International Nuclear Information System (INIS)

    Zeta-crystallin-like quinone oxidoreductase is NAD(P)H-dependent and catalyzes one-electron reduction of certain quinones to generate semiquinone. Here we present the crystal structures of zeta-crystallin-like quinone oxidoreductase from Pseudomonas syringae pv. tomato DC3000 (PtoQOR) and its complexes with NADPH determined at 2.4 and 2.01 A resolutions, respectively. PtoQOR forms as a homologous dimer, each monomer containing two domains. In the structure of the PtoQOR-NADPH complex, NADPH locates in the groove between the two domains. NADPH binding causes obvious conformational changes in the structure of PtoQOR. The putative substrate-binding site of PtoQOR is wider than that of Escherichia coli and Thermus thermophilus HB8. Activity assays show that PtoQOR has weak 1,4-benzoquinone catalytic activity, and very strong reduction activity towards large substrates such as 9,10-phenanthrenequinone. We propose a model to explain the conformational changes which take place during reduction reactions catalyzed by PtoQOR.

  3. Mass Transfer in Amperometric Biosensors Based on Nanocomposite Thin Films of Redox Polymers and Oxidoreductases

    Directory of Open Access Journals (Sweden)

    Aleksandr L. Simonian

    2002-03-01

    Full Text Available Mass transfer in nanocomposite hydrogel thin films consisting of alternating layers of an organometallic redox polymer (RP and oxidoreductase enzymes was investigated. Multilayer nanostructures were fabricated on gold surfaces by the deposition of an anionic self-assembled monolayer of 11-mercaptoundecanoic acid, followed by the electrostatic binding of a cationic redox polymer, poly[vinylpyridine Os(bis-bipyridine2Clco-allylamine], and an anionic oxidoreductase. Surface plasmon resonance spectroscopy, Fourier transform infrared external reflection spectroscopy (FTIR-ERS, ellipsometry and electrochemistry were employed to characterize the assembly of these nanocomposite films. Simultaneous SPR/electrochemistry enabled real time observation of the assembly of sensing components, changes in film structure with electrode potential, and the immediate, in situ electrochemical verification of substrate-dependent current upon the addition of enzyme to the multilayer structure. SPR and FTIR-ERS studies also showed no desorption of polymer or enzyme from the nanocomposite structure when stored in aqueous environment occurred over the period of three weeks, suggesting that decreasing in substrate sensitivity were due to loss of enzymatic activity rather than loss of film compounds from the nanostructure.

  4. Homology modeling and in silico site directed mutagenesis of pyruvate ferredoxin oxidoreductase from Clostridium thermocellum.

    Science.gov (United States)

    Saranyah, Kannuchamy; Kalva, Sukesh; Mukund, Nisha; Singh, Sanjeev Kumar; Saleena, Lilly M

    2015-01-01

    Pyruvate ferredoxin oxidoreductase is the crucial enzyme that involves in bioethanol synthesis pathway of Clostridium thermocellum. It is an ethanologenic organism but has been investigated less on its enzyme structure. The amino acid sequence of Pyruvate ferredoxin oxidoreductase was derived from UNIPROT and the screened crystal structure was taken as the template for homology modeling using MODELLER 9V11. The model was loop refined and was validated using RMSD, ProSA and PROCHECK. The docking and per residue interaction studies were carried out to elucidate the interaction energies of amino acid residues with pyruvate. To enhance the binding of pyruvate with the enzyme, mutation studies were carried out by replacing Thr31 as it had a less interaction energy. Out of 10 mutants, T31N, T31Q and T31G were selected using potential energy and the residual energy calculations. Five nanoseconds explicit MD simulations were run for apo, wild type and mutants T31N, T31Q and T31G using Desmond. RMSD, RMSF, distance plots and H-bonds analysis proved T31G to be a favorable mutant for binding of pyruvate. Thus, modeling PFOR would help in profound understanding of its structural clefts and mutation studies would aid in improving the enzyme efficiency. PMID:26369404

  5. Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex.

    Science.gov (United States)

    Dyall, Sabrina D; Yan, Weihong; Delgadillo-Correa, Maria G; Lunceford, Adam; Loo, Joseph A; Clarke, Catherine F; Johnson, Patricia J

    2004-10-28

    Trichomonas vaginalis is a unicellular microaerophilic eukaryote that lacks mitochondria yet contains an alternative organelle, the hydrogenosome, involved in pyruvate metabolism. Pathways between the two organelles differ substantially: in hydrogenosomes, pyruvate oxidation is catalysed by pyruvate:ferredoxin oxidoreductase (PFOR), with electrons donated to an [Fe]-hydrogenase which produces hydrogen. ATP is generated exclusively by substrate-level phosphorylation in hydrogenosomes, as opposed to oxidative phosphorylation in mitochondria. PFOR and hydrogenase are found in eubacteria and amitochondriate eukaryotes, but not in typical mitochondria. Analyses of mitochondrial genomes indicate that mitochondria have a single endosymbiotic origin from an alpha-proteobacterial-type progenitor. The absence of a genome in trichomonad hydrogenosomes precludes such comparisons, leaving the endosymbiotic history of this organelle unclear. Although phylogenetic reconstructions of a few proteins indicate that trichomonad hydrogenosomes share a common origin with mitochondria, others do not. Here we describe a novel NADH dehydrogenase module of respiratory complex I that is coupled to the central hydrogenosomal fermentative pathway to form a hydrogenosomal oxidoreductase complex that seems to function independently of quinones. Phylogenetic analyses of hydrogenosomal complex I-like proteins Ndh51 and Ndh24 reveal that neither has a common origin with mitochondrial homologues. These studies argue against a vertical origin of trichomonad hydrogenosomes from the proto-mitochondrial endosymbiont. PMID:15510149

  6. Tetrazolium-dye-linked alcohol dehydrogenase of the methylotrophic actinomycete Amycolatopsis methanolica is a three-component complex

    OpenAIRE

    Bystrykh, LV; GOVORUKHINA, NI; Dijkhuizen, L.; Duine, JA; Govorukhina, Natalya I.; Duine, Johannis A.

    1997-01-01

    Tetrazolium-dye-linked alcohol dehydrogenase (TD-ADH) of Amycolatopsis methanolica could be resolved into three protein components, which have been purified. Each of the components has the ability to reconstitute TD-ADH activity when combined with the other two. Component I is identical to the previously characterized methanol :N:N'-dimethyl-4-nitrosoaniline oxidoreductase (MNO), a decameric protein with 50-kDa subunits, each carrying a tightly bound NADPH. Component 2 is a high molecular mas...

  7. Alcoholism (image)

    Science.gov (United States)

    ... that interferes with physical or mental health, and social, family or job responsibilities. This addiction can lead to liver, circulatory and neurological problems. Pregnant women who drink alcohol in any amount ...

  8. PURIFICATION AND CHARACTERIZATION OF A BENZYLVIOLOGEN-LINKED, TUNGSTEN-CONTAINING ALDEHYDE OXIDOREDUCTASE FROM DESULFOVIBRIO-GIGAS

    NARCIS (Netherlands)

    HENSGENS, CMH; HAGEN, WR; HANSEN, TA

    1995-01-01

    Desulfovibrio gigas NCIMB 9332 cells grown in ethanol-containing medium with 0.1 mu M tungstate contained a benzylviologen-linked aldehyde oxidoreductase, The enzyme was purified to electrophoretic homogeneity and found to be a homodimer with a subunit M(r) of 62,000, It contained 0.68 a 0.08 W, 4.8

  9. Characteristics of endogenous flavin fluorescence of Photobacterium leiognathi luciferase and Vibrio fisheri NAD(P)H:FMN-oxidoreductase

    NARCIS (Netherlands)

    Vetrova, E.V.; Kudryasheva, N.S.; Visser, A.J.W.G.; Hoek, van A.

    2005-01-01

    The bioluminescent bacterial enzyme system NAD(P)H:FMN-oxidoreductase-luciferase has been used as a test system for ecological monitoring. One of the modes to quench bioluminescence is the interaction of xenobiotics with the enzymes, which inhibit their activity. The use of endogenous flavin fluores

  10. Pyruvate Oxidoreductases Involved in Glycolytic Anaerobic Metabolism of Polychaetes from the Continental Shelf off Central-South Chile

    Science.gov (United States)

    González, R. R.; Quiñones, R. A.

    2000-10-01

    The presence of low oxygen conditions in extensive areas of the continental shelf off central-south Chile has important effects on the biochemical adaptations of the organisms living in this ecosystem. Polychaetes assemblages cohabit on the shelf with an extensively distributed prokaryotic community made up of giant filamentous sulfur bacteria (mainly Thioploca sp.). The aim of this research was to characterize the pyruvate oxidoreductases enzymes involved in the biochemical adaptation of these benthic polychaetes. Nine polychaete species ( Paraprionospio pinnata, Nephtys ferruginea, Glycera americana, Haploscoloplos sp., Lumbrineris composita, Sigambra bassi, Aricidea pigmentata , Cossura chilensis, and Pectinaria chilensis) were assayed for lactic dehydrogenase (LDH), octopine dehydrogenase (OPDH), strombine dehydrogenase (STRDH) and alanopine dehydrogenase (ALPDH). Each species had a characteristic number of the pyruvate oxidoreductases assayed ranging from 4 in Paraprionospio pinnata to 1 in Pectinaria chilensis . The pyruvate saturation curves obtained for the enzymes from all species analysed, except L. composita, suggest that NADH can be oxidized at different rates depending on the amino acid used in the reaction with pyruvate. Our results indicate that organisms having more that one pyruvate oxidoreductase present a greater metabolic capacity to cope with functional and environmental hypoxia because these enzymes would better regulate the pyruvate consumption rate during the transition period. Thus, the dominance of Paraprionospio pinnata in the study area and its worldwide distribution is consistent with its higher number of pyruvate oxidoreductases with different pyruvate consumption rates involved in anaerobic metabolism. Finally, a positive allometric relationship was found between body size and the specific activity of ALPDH, STRDH, and maximum pyruvate oxidoreductase specific activity. This latter result suggests a positive scaling of the specific

  11. Structural domains in NADPH: Protochlorophyllide oxidoreductases involved in catalysis and substrate binding. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Timko, Michael P.

    1999-09-24

    Until recently little direct information was available about specific structural determinants within the light-dependent NADPH: protochlorophyllide oxidoreductases (PORs) required for substrate and cofactor binding, catalytic activity, and thylakoid membrane localization. Based on our previous DOE-funded studies, during the past year we brought to fruition a number of ongoing experiments, initiated several new avenues of investigations, and overall have made considerable progress towards establishing the basic structural parameters governing POR function. Our studies to date have defined residues and domains involved in substrate and cofactor binding and catalysis, and elaborated on the mechanism for membrane localization of POR in developing plastids. Our results and their significance, as well as our work in progress, are detailed.

  12. Regulation of adhE (Encoding Ethanol Oxidoreductase) by the Fis Protein in Escherichia coli

    Science.gov (United States)

    Membrillo-Hernández, Jorge; Kwon, Ohsuk; De Wulf, Peter; Finkel, Steven E.; Lin, E. C. C.

    1999-01-01

    The adhE gene of Escherichia coli encodes a multifunctional ethanol oxidoreductase whose expression is 10-fold higher under anaerobic than aerobic conditions. Transcription of the gene is under the negative control of the Cra (catabolite repressor-activator) protein, whereas translation of the adhE mRNA requires processing by RNase III. In this report, we show that the expression of adhE also depends on the Fis (factor for inversion stimulation) protein. A strain bearing a fis::kan null allele failed to grow anaerobically on glucose solely because of inadequate adhE transcription. However, fis expression itself is not under redox control. Sequence inspection of the adhE promoter revealed three potential Fis binding sites. Electrophoretic mobility shift analysis, using purified Fis protein and adhE promoter DNA, showed three different complexes. PMID:10572146

  13. NADPH: Protochlorophyllide Oxidoreductase-Structure, Catalytic Function, and Role in Prolamellar Body Formation and Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Timko, Michael P

    2013-02-01

    The biosynthesis of chlorophyll is a critical biochemical step in the development of photosynthetic vascular plants and green algae. From photosynthetic bacteria (cyanobacteria) to algae, non-vascular plants, gymnosperms and vascular plants, mechanisms have evolved for protochlorophyllide reduction a key step in chlorophyll synthesis. Protochlorophyllide reduction is carried out by both a light-dependent (POR) and light-independent (LIPOR) mechanisms. NADPH: protochlorophyllide oxidoreductase (EC 1.3.1.33, abbreviated POR) catalyzes the light-dependent reduction of protochlorophyllide (PChlide) to chlorophyllide (Chlide). In contrast, a light-independent protochlorophyllide reductase (LIPOR) involves three plastid gene products (chlL, chlN, and chlB) and several nuclear factors. Our work focused on characterization of both the POR and LIPOR catalyzed processes.

  14. A novel insight into the oxidoreductase activity of Helicobacter pylori HP0231 protein.

    Directory of Open Access Journals (Sweden)

    Paula Roszczenko

    Full Text Available BACKGROUND: The formation of a disulfide bond between two cysteine residues stabilizes protein structure. Although we now have a good understanding of the Escherichia coli disulfide formation system, the machineries at work in other bacteria, including pathogens, are poorly characterized. Thus, the objective of this work was to improve our understanding of the disulfide formation machinery of Helicobacter pylori, a leading cause of ulcers and a risk factor for stomach cancer worldwide. METHODS AND RESULTS: The protein HP0231 from H. pylori, a structural counterpart of E. coli DsbG, is the focus of this research. Its function was clarified by using a combination of biochemical, microbiological and genetic approaches. In particular, we determined the biochemical properties of HP0231 as well as its redox state in H. pylori cells. CONCLUSION: Altogether our results show that HP0231 is an oxidoreductase that catalyzes disulfide bond formation in the periplasm. We propose to call it HpDsbA.

  15. Characterization of a unique Caulobacter crescentus aldose-aldose oxidoreductase having dual activities.

    Science.gov (United States)

    Andberg, Martina; Maaheimo, Hannu; Kumpula, Esa-Pekka; Boer, Harry; Toivari, Mervi; Penttilä, Merja; Koivula, Anu

    2016-01-01

    We describe here the characterization of a novel enzyme called aldose-aldose oxidoreductase (Cc AAOR; EC 1.1.99) from Caulobacter crescentus. The Cc AAOR exists in solution as a dimer, belongs to the Gfo/Idh/MocA family and shows homology with the glucose-fructose oxidoreductase from Zymomonas mobilis. However, unlike other known members of this protein family, Cc AAOR is specific for aldose sugars and can be in the same catalytic cycle both oxidise and reduce a panel of monosaccharides at the C1 position, producing in each case the corresponding aldonolactone and alditol, respectively. Cc AAOR contains a tightly-bound nicotinamide cofactor, which is regenerated in this oxidation-reduction cycle. The highest oxidation activity was detected on D-glucose but significant activity was also observed on D-xylose, L-arabinose and D-galactose, revealing that both hexose and pentose sugars are accepted as substrates by Cc AAOR. The configuration at the C2 and C3 positions of the saccharides was shown to be especially important for the substrate binding. Interestingly, besides monosaccharides, Cc AAOR can also oxidise a range of 1,4-linked oligosaccharides having aldose unit at the reducing end, such as lactose, malto- and cello-oligosaccharides as well as xylotetraose. (1)H NMR used to monitor the oxidation and reduction reaction simultaneously, demonstrated that although D-glucose has the highest affinity and is also oxidised most efficiently by Cc AAOR, the reduction of D-glucose is clearly not as efficient. For the overall reaction catalysed by Cc AAOR, the L-arabinose, D-xylose and D-galactose were the most potent substrates.

  16. Alcohol and Hepatitis C

    Science.gov (United States)

    ... code here Enter ZIP code here Daily Living: Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one ... related to choices you make about your lifestyle . Alcohol and fibrosis Fibrosis is the medical term for ...

  17. Alcohol use disorder

    Science.gov (United States)

    Alcohol use disorder is when your drinking causes serious problems in your life, yet you keep drinking. You may ... alcohol content). If you have a parent with alcohol use disorder, you are more at risk for alcohol problems. ...

  18. Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

    Science.gov (United States)

    Rizzo, William B.

    2014-01-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. PMID:24036493

  19. Increased Furfural Tolerance Due to Overexpression of NADH-Dependent Oxidoreductase FucO in Escherichia coli Strains Engineered for the Production of Ethanol and Lactate▿

    OpenAIRE

    X. Wang; Miller, E. N.; Yomano, L. P.; Zhang, X.; Shanmugam, K. T.; Ingram, L. O.

    2011-01-01

    Furfural is an important fermentation inhibitor in hemicellulose sugar syrups derived from woody biomass. The metabolism of furfural by NADPH-dependent oxidoreductases, such as YqhD (low Km for NADPH), is proposed to inhibit the growth and fermentation of xylose in Escherichia coli by competing with biosynthesis for NADPH. The discovery that the NADH-dependent propanediol oxidoreductase (FucO) can reduce furfural provided a new approach to improve furfural tolerance. Strains that produced eth...

  20. Over-expression of a putative oxidoreductase (UcpA) for increasing furfural or 5-hydroxymethylfurfural tolerance

    Science.gov (United States)

    Wang, Xuan; Miller, Elliot N.; Yomano, Lorraine P.; Shanmugam, Keelnatham T.; Ingram, Lonnie O'Neal

    2016-05-24

    The subject invention pertains to overexpression of a putative oxidoreductase (ucpA) for increasing furfural tolerance in genetically modified microorganisms. Genetically modified microorganisms capable of overexpressing UcpA are also provided. Increased expression of ucpA was shown to increase furfural tolerance by 50%, and to permit the fermentation of sugars to products in the presence of 15 mM furfural.

  1. Over-expression of NADH-dependent oxidoreductase (fucO) for increasing furfural or 5-hydroxymethylfurfural tolerance

    Science.gov (United States)

    Miller, Elliot N.; Zhang, Xueli; Yomano, Lorraine P.; Wang, Xuan; Shanmugam, Keelnatham T.; Ingram, Lonnie O'Neal

    2015-10-13

    The subject invention pertains to the discovery that the NADH-dependent propanediol oxidoreductase (FucO) can reduce furfural. This allows for a new approach to improve furfural tolerance in bacterial and/or yeast cells used to produce desired products. Thus, novel biocatalysts (bacterial, fungal or yeast cells) exhibiting increased tolerance to furfural and 5-hydroxymethylfurfural (5-HMF) are provided as are methods of making and using such biocatalysts for the production of a desired product.

  2. Role of cysteine-58 and cysteine-95 residues in the thiol di-sulfide oxidoreductase activity of Macrophage Migration Inhibitory Factor-2 of Wuchereria bancrofti.

    Science.gov (United States)

    Chauhan, Nikhil; Hoti, S L

    2016-01-01

    Macrophage Migration Inhibitory Factor (MIF) is the first human cytokine reported and was thought to have a central role in the regulation of inflammatory responses. Homologs of this molecule have been reported in bacteria, invertebrates and plants. Apart from cytokine activity, it also has two catalytic activities viz., tautomerase and di-sulfide oxidoreductase, which appear to be involved in immunological functions. The CXXC catalytic site is responsible for di-sulfide oxidoreductase activity of MIF. We have recently reported thiol-disulfide oxidoreductase activity of Macrophage Migration Inhibitory Factor-2 of Wuchereria bancrofti (Wba-MIF-2), although it lacks the CXXC motif. We hypothesized that three conserved cysteine residues might be involved in the formation of di-sulfide oxidoreductase catalytic site. Homology modeling of Wba-MIF-2 showed that among the three cysteine residues, Cys58 and Cys95 residues came in close proximity (3.23Å) in the tertiary structure with pKa value 9, indicating that these residues might play a role in the di-sulfide oxidoreductase catalytic activity. We carried out site directed mutagenesis of these residues (Cys58Ser & Cys95Ser) and expressed mutant proteins in Escherichia coli. The mutant proteins did not show any oxidoreductase activity in the insulin reduction assay, thus indicating that these two cysteine residues are vital for the catalytic activity of Wba-MIF-2. PMID:26432350

  3. Alcohol Consumption and Alcohol Advertising Bans

    OpenAIRE

    Henry Saffer

    2000-01-01

    The purpose of this paper is to empirically examine the relationship between alcohol advertising bans and alcohol consumption. Most prior studies have found no effect of advertising on total alcohol consumption. A simple economic model is provided which explains these prior results. The data set used in this study is a pooled time series of data from 20 countries over 26 years. The empirical model is a simultaneous equations system which treats both alcohol consumption and alcohol advertising...

  4. Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans

    Directory of Open Access Journals (Sweden)

    Takeshi Nishino

    2012-11-01

    Full Text Available Xanthine oxidoreductase (XOR catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD+ or O2. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors.

  5. Assembly of the Escherichia coli NADH:ubiquinone oxidoreductase (respiratory complex I).

    Science.gov (United States)

    Friedrich, Thorsten; Dekovic, Doris Kreuzer; Burschel, Sabrina

    2016-03-01

    Energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, couples the electron transfer from NADH to ubiquinone with the translocation of four protons across the membrane. The Escherichia coli complex I is made up of 13 different subunits encoded by the so-called nuo-genes. The electron transfer is catalyzed by nine cofactors, a flavin mononucleotide and eight iron-sulfur (Fe/S)-clusters. The individual subunits and the cofactors have to be assembled together in a coordinated way to guarantee the biogenesis of the active holoenzyme. Only little is known about the assembly of the bacterial complex compared to the mitochondrial one. Due to the presence of so many Fe/S-clusters the assembly of complex I is intimately connected with the systems responsible for the biogenesis of these clusters. In addition, a few other proteins have been reported to be required for an effective assembly of the complex in other bacteria. The proposed role of known bacterial assembly factors is discussed and the information from other bacterial species is used in this review to draw an as complete as possible model of bacterial complex I assembly. In addition, the supramolecular organization of the complex in E. coli is briefly described. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Prof. Conrad Mullineaux.

  6. Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury

    Institute of Scientific and Technical Information of China (English)

    Lauren M Aleksunes; Michael Goedken; José E Manautou

    2006-01-01

    AIM: To investigate the expression and activity of NAD(P)H quinone oxidoreductase 1 (NQO1) in human liver specimens obtained from patients with liver damage due to acetaminophen (APAP) overdose or primary biliary cirrhosis (PBC).METHODS: NQO1 activity was determined in cytosol from normal, APAP and PBC liver specimens. Western blot and immunohistochemical staining were used to determine patterns of NQO1 expression using a specific antibody against NQO1.RESULTS: NQO1 protein was very low in normal human livers. In both APAP and PBC livers, there was strong induction of NQO1 protein levels on Western blot.Correspondingly, significant up-regulation of enzyme activity (16- and 22-fold, P< 0.05) was also observed in APAP and PBC livers, respectively. Immunohistochemical analysis highlighted injury-specific patterns of NQO1 staining in both APAP and PBC livers.CONCLUSION: These data demonstrate that NQO1 protein and activity are markedly induced in human livers during both APAP overdose and PBC. Up-regulation of this cytoprotective enzyme may represent an adaptive stress response to limit further disease progression by detoxifying reactive species.

  7. GltX from Clostridium saccharobutylicum NCP262: glutamate synthase or oxidoreductase?

    Science.gov (United States)

    Stutz, Helen E; Reid, Sharon J

    2004-01-01

    A full-length gene encoding a homologue of the small subunit of the glutamate synthase (GOGAT) enzyme was isolated from the anaerobic bacterium, Clostridium saccharobutylicum NCP262, which has been used extensively for the commercial production of solvents. Using a screening system designed to isolate genes involved in electron transport, plasmid pMET13C1 was isolated. Analysis of this plasmid identified a gene (1245 bp) with a predicted approximately 46-kDa product, which was associated with reductive activation of the pro-drug metronidazole. The deduced 414-amino-acid sequence was not typical of electron transport proteins, but rather shared striking homology to the small (beta) subunit of the GOGAT enzyme and other beta subunit-like polypeptides, and was thus designated gltX. Although all the functional domains typical of GOGAT beta subunits were conserved in this GltX protein, certain sequence features were not conserved. Furthermore, it was independently transcribed, did not lie adjacent to a GOGAT large subunit (alpha) domain, and its expression was not regulated by nitrogen conditions. These results provide additional support for current theories on the evolutionary relationships of GOGAT beta subunit domains in bacteria, and suggest that GltX belongs to a more general family of oxidoreductases, which is used in a context other than glutamate biosynthesis to transfer electrons to a currently unknown protein domain. PMID:14732492

  8. Untargeted plasma metabolite profiling reveals the broad systemic consequences of xanthine oxidoreductase inactivation in mice.

    Directory of Open Access Journals (Sweden)

    Qiuying Chen

    Full Text Available A major challenge in systems biology is integration of molecular findings for individual enzyme activities into a cohesive high-level understanding of cellular metabolism and physiology/pathophysiology. However, meaningful prediction for how a perturbed enzyme activity will globally impact metabolism in a cell, tissue or intact organisms is precluded by multiple unknowns, including in vivo enzymatic rates, subcellular distribution and pathway interactions. To address this challenge, metabolomics offers the potential to simultaneously survey changes in thousands of structurally diverse metabolites within complex biological matrices. The present study assessed the capability of untargeted plasma metabolite profiling to discover systemic changes arising from inactivation of xanthine oxidoreductase (XOR, an enzyme that catalyzes the final steps in purine degradation. Using LC-MS coupled with a multivariate statistical data analysis platform, we confidently surveyed >3,700 plasma metabolites (50-1,000 Da for differential expression in XOR wildtype vs. mice with inactivated XOR, arising from gene deletion or pharmacological inhibition. Results confirmed the predicted derangements in purine metabolism, but also revealed unanticipated perturbations in metabolism of pyrimidines, nicotinamides, tryptophan, phospholipids, Krebs and urea cycles, and revealed kidney dysfunction biomarkers. Histochemical studies confirmed and characterized kidney failure in xor-nullizygous mice. These findings provide new insight into XOR functions and demonstrate the power of untargeted metabolite profiling for systemic discovery of direct and indirect consequences of gene mutations and drug treatments.

  9. One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography

    Science.gov (United States)

    Chen, Percival Yang-Ting; Johnson, Aileen C.; Pierce, Elizabeth; Can, Mehmet; Ragsdale, Stephen W.; Drennan, Catherine L.

    2016-01-01

    Thiamine pyrophosphate (TPP)-dependent oxalate oxidoreductase (OOR) metabolizes oxalate, generating two molecules of CO2 and two low-potential electrons, thus providing both the carbon and reducing equivalents for operation of the Wood−Ljungdahl pathway of acetogenesis. Here we present structures of OOR in which two different reaction intermediate bound states have been trapped: the covalent adducts between TPP and oxalate and between TPP and CO2. These structures, along with the previously determined structure of substrate-free OOR, allow us to visualize how active site rearrangements can drive catalysis. Our results suggest that OOR operates via a bait-and-switch mechanism, attracting substrate into the active site through the presence of positively charged and polar residues, and then altering the electrostatic environment through loop and side chain movements to drive catalysis. This simple but elegant mechanism explains how oxalate, a molecule that humans and most animals cannot break down, can be used for growth by acetogenic bacteria. PMID:26712008

  10. NAD(P)H:quinone oxidoreductase 1 inducer activity of some novel anilinoquinazoline derivatives

    Science.gov (United States)

    Ghorab, Mostafa M; Alsaid, Mansour S; Higgins, Maureen; Dinkova-Kostova, Albena T; Shahat, Abdelaaty A; Elghazawy, Nehal H; Arafa, Reem K

    2016-01-01

    The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements pathway enables cells to survive oxidative stress conditions through regulating the expression of cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1). This work presents the design and synthesis of novel anilinoquinazoline derivatives (2–16a) and evaluation of their NQO1 inducer activity in murine cells. Molecular docking of the new compounds was performed to assess their ability to inhibit Keap1–Nrf2 protein–protein interaction through occupying the Keap1–Nrf2-binding domain, which leads to Nrf2 accumulation and enhanced gene expression of NQO1. Docking results showed that all compounds can potentially interact with Keap1; however, 1,5-dimethyl-2-phenyl-4-(2-phenylquinazolin-4-ylamino)-1,2-dihydropyrazol-3-one (9), the most potent inducer, showed the largest number of interactions with key amino acids in the binding pocket (Arg483, Tyr525, and Phe478) compared to the native ligand or any other compound in this series. PMID:27540279

  11. Pulsed electron paramagnetic resonance experiments identify the paramagnetic intermediates in the pyruvate ferredoxin oxidoreductase catalytic cycle.

    Science.gov (United States)

    Astashkin, Andrei V; Seravalli, Javier; Mansoorabadi, Steven O; Reed, George H; Ragsdale, Stephen W

    2006-03-29

    Pyruvate ferredoxin oxidoreductase (PFOR) is central to the anaerobic metabolism of many bacteria and amitochondriate eukaryotes. PFOR contains thiamine pyrophosphate (TPP) and three [4Fe-4S] clusters, which link pyruvate oxidation to reduction of ferredoxin. In the PFOR reaction, TPP reacts with pyruvate to form lactyl-TPP, which undergoes decarboxylation to form a hydroxyethyl-TPP (HE-TPP) intermediate. One electron is then transferred from HE-TPP to one of the three [4Fe-4S] clusters to form an HE-TPP radical and a [4Fe-4S]1+ intermediate. Pulsed EPR methods have been used to measure the distance between the HE-TPP radical and the [4Fe-4S]1+ cluster to which it is coupled. Computational analysis including the PFOR crystal structure and the spin distribution in the HE-TPP radical and in the reduced [4Fe-4S] cluster demonstrates that the distance between the HE-TPP radical and the medial cluster B matches the experimentally determined dipolar interaction, while one of the other two clusters is too close and the other is too far away. These results clearly demonstrate that it is the medial cluster (cluster B) that is reduced. Thus, rapid electron transfer occurs through the electron-transfer chain, which leaves an oxidized proximal cluster poised to accept an electron from the HE-TPP radical in the subsequent reaction step. PMID:16551078

  12. Crystal structure of the free radical intermediate of pyruvate:ferredoxin oxidoreductase.

    Science.gov (United States)

    Chabrière, E; Vernède, X; Guigliarelli, B; Charon, M H; Hatchikian, E C; Fontecilla-Camps, J C

    2001-12-21

    In anaerobic organisms, the decarboxylation of pyruvate, a crucial component of intermediary metabolism, is catalyzed by the metalloenzyme pyruvate: ferredoxin oxidoreductase (PFOR) resulting in the generation of low potential electrons and the subsequent acetylation of coenzyme A (CoA). PFOR is the only enzyme for which a stable acetyl thiamine diphosphate (ThDP)-based free radical reaction intermediate has been identified. The 1.87 A-resolution structure of the radical form of PFOR from Desulfovibrio africanus shows that, despite currently accepted ideas, the thiazole ring of the ThDP cofactor is markedly bent, indicating a drastic reduction of its aromaticity. In addition, the bond connecting the acetyl group to ThDP is unusually long, probably of the one-electron type already described for several cation radicals but not yet found in a biological system. Taken together, our data, along with evidence from the literature, suggest that acetyl-CoA synthesis by PFOR proceeds via a condensation mechanism involving acetyl (PFOR-based) and thiyl (CoA-based) radicals. PMID:11752578

  13. Influence of 120 kDa Pyruvate:Ferredoxin Oxidoreductase on Pathogenicity of Trichomonas vaginalis.

    Science.gov (United States)

    Song, Hyun-Ouk

    2016-02-01

    Trichomonas vaginalis is a flagellate protozoan parasite and commonly infected the lower genital tract in women and men. Iron is a known nutrient for growth of various pathogens, and also reported to be involved in establishment of trichomoniasis. However, the exact mechanism was not clarified. In this study, the author investigated whether the 120 kDa protein of T. vaginalis may be involved in pathogenicity of trichomonads. Antibodies against 120 kDa protein of T. vaginalis, which was identified as pyruvate:ferredoxin oxidoreductase (PFOR) by peptide analysis of MALDI-TOF-MS, were prepared in rabbits. Pretreatment of T. vaginalis with anti-120 kDa Ab decreased the proliferation and adherence to vaginal epithelial cells (MS74) of T. vaginalis. Subcutaneous tissue abscess in anti-120 kDa Ab-treated T. vaginalis-injected mice was smaller in size than that of untreated T. vaginalis-infected mice. Collectively, the 120 kDa protein expressed by iron may be involved in proliferation, adhesion to host cells, and abscess formation, thereby may influence on the pathogenicity of T. vaginalis. PMID:26951982

  14. Breath alcohol test

    Science.gov (United States)

    Alcohol test - breath ... There are various brands of breath alcohol tests. Each one uses a different method to test the level of alcohol in the breath. The machine may be electronic or manual. One ...

  15. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  16. Behind the Label "Alcoholic."

    Science.gov (United States)

    Wright, Deborah M.

    1989-01-01

    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  17. Genetics and alcoholism

    OpenAIRE

    Edenberg, Howard J.; Foroud, Tatiana

    2013-01-01

    Alcohol is widely consumed, but excessive use creates serious physical, psychological and social problems and contributes to many diseases. Alcoholism (alcohol dependence, alcohol use disorders) is a maladaptive pattern of excessive drinking leading to serious problems. Abundant evidence indicates that alcoholism is a complex genetic disease, with variations in a large number of genes affecting risk. Some of these genes have been identified, including two genes of alcohol me...

  18. ALCOHOL AND ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2014-01-01

    Full Text Available The article considers the questions of the relationship between the amount of the consumed alcohol, the type of alcoholic beverage, pattern of alcohol consumption and the blood pressure level. The article presents data on the positive effect of alcohol intake restrictions and recommendations for permissible limits of alcohol consumption. New possibilities of drug therapy aimed at limiting alcohol consumption are being reported.

  19. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    DEFF Research Database (Denmark)

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren;

    2008-01-01

    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may...... be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking...... and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men...

  20. Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Chuanwu; Panda, Satya P.; Marohnic, Christopher C.; Martásek, Pavel; Masters, Bettie Sue; Kim, Jung-Ja P. (MCW); (Charles U); (UTSMC)

    2012-03-15

    NADPH-cytochrome P450 oxidoreductase (CYPOR) is essential for electron donation to microsomal cytochrome P450-mediated monooxygenation in such diverse physiological processes as drug metabolism (approximately 85-90% of therapeutic drugs), steroid biosynthesis, and bioactive metabolite production (vitamin D and retinoic acid metabolites). Expressed by a single gene, CYPOR's role with these multiple redox partners renders it a model for understanding protein-protein interactions at the structural level. Polymorphisms in human CYPOR have been shown to lead to defects in bone development and steroidogenesis, resulting in sexual dimorphisms, the severity of which differs significantly depending on the degree of CYPOR impairment. The atomic structure of human CYPOR is presented, with structures of two naturally occurring missense mutations, V492E and R457H. The overall structures of these CYPOR variants are similar to wild type. However, in both variants, local disruption of H bonding and salt bridging, involving the FAD pyrophosphate moiety, leads to weaker FAD binding, unstable protein, and loss of catalytic activity, which can be rescued by cofactor addition. The modes of polypeptide unfolding in these two variants differ significantly, as revealed by limited trypsin digestion: V492E is less stable but unfolds locally and gradually, whereas R457H is more stable but unfolds globally. FAD addition to either variant prevents trypsin digestion, supporting the role of the cofactor in conferring stability to CYPOR structure. Thus, CYPOR dysfunction in patients harboring these particular mutations may possibly be prevented by riboflavin therapy in utero, if predicted prenatally, or rescued postnatally in less severe cases.

  1. Chlamydomonas reinhardtii chloroplasts contain a homodimeric pyruvate:ferredoxin oxidoreductase that functions with FDX1.

    Science.gov (United States)

    van Lis, Robert; Baffert, Carole; Couté, Yohann; Nitschke, Wolfgang; Atteia, Ariane

    2013-01-01

    Eukaryotic algae have long been known to live in anoxic environments, but interest in their anaerobic energy metabolism has only recently gained momentum, largely due to their utility in biofuel production. Chlamydomonas reinhardtii figures remarkably in this respect, because it efficiently produces hydrogen and its genome harbors many genes for anaerobic metabolic routes. Central to anaerobic energy metabolism in many unicellular eukaryotes (protists) is pyruvate:ferredoxin oxidoreductase (PFO), which decarboxylates pyruvate and forms acetyl-coenzyme A with concomitant reduction of low-potential ferredoxins or flavodoxins. Here, we report the biochemical properties of the homodimeric PFO of C. reinhardtii expressed in Escherichia coli. Electron paramagnetic resonance spectroscopy of the recombinant enzyme (Cr-rPFO) showed three distinct [4Fe-4S] iron-sulfur clusters and a thiamine pyrophosphate radical upon reduction by pyruvate. Purified Cr-rPFO exhibits a specific decarboxylase activity of 12 µmol pyruvate min⁻¹ mg⁻¹ protein using benzyl viologen as electron acceptor. Despite the fact that the enzyme is very oxygen sensitive, it localizes to the chloroplast. Among the six known chloroplast ferredoxins (FDX1-FDX6) in C. reinhardtii, FDX1 and FDX2 were the most efficient electron acceptors from Cr-rPFO, with comparable apparent K(m) values of approximately 4 µm. As revealed by immunoblotting, anaerobic conditions that lead to the induction of CrPFO did not increase levels of either FDX1 or FDX2. FDX1, being by far the most abundant ferredoxin, is thus likely the partner of PFO in C. reinhardtii. This finding postulates a direct link between CrPFO and hydrogenase and provides new opportunities to better study and engineer hydrogen production in this protist. PMID:23154536

  2. Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury.

    Science.gov (United States)

    Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Hibi, Chihiro; Nakamura, Takashi; Murase, Takayo; Oikawa, Tsuyoshi; Hoshino, Seiko; Hisamichi, Mikako; Hirata, Kazuaki; Kimura, Kenjiro; Shibagaki, Yugo

    2016-06-01

    The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model. PMID:27029427

  3. Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury.

    Science.gov (United States)

    Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Hibi, Chihiro; Nakamura, Takashi; Murase, Takayo; Oikawa, Tsuyoshi; Hoshino, Seiko; Hisamichi, Mikako; Hirata, Kazuaki; Kimura, Kenjiro; Shibagaki, Yugo

    2016-06-01

    The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.

  4. Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat brain.

    Science.gov (United States)

    Hall, Catherine N; Keynes, Robert G; Garthwaite, John

    2009-04-15

    In low nanomolar concentrations, NO (nitric oxide) functions as a transmitter in brain and other tissues, whereas near-micromolar NO concentrations are associated with toxicity and cell death. Control of the NO concentration, therefore, is critical for proper brain function, but, although its synthesis pathway is well-characterized, the major route of breakdown of NO in brain is unclear. Previous observations indicate that brain cells actively consume NO at a high rate. The mechanism of this consumption was pursued in the present study. NO consumption by a preparation of central glial cells was abolished by cell lysis and recovered by addition of NADPH. NADPH-dependent consumption of NO localized to cell membranes and was inhibited by proteinase K, indicating the involvement of a membrane-bound protein. Purification of this activity yielded CYPOR (cytochrome P450 oxidoreductase). Antibodies against CYPOR inhibited NO consumption by brain membranes and the amount of CYPOR in several cell types correlated with their rate of NO consumption. NO was also consumed by purified CYPOR but this activity was found to depend on the presence of the vitamin E analogue Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), included in the buffer as a precaution against inadvertent NO consumption by lipid peroxidation. In contrast, NO consumption by brain membranes was independent of Trolox. Hence, it appears that, during the purification process, CYPOR becomes separated from a partner needed for NO consumption. Cytochrome P450 inhibitors inhibited NO consumption by brain membranes, making these proteins likely candidates.

  5. Mechanistic reappraisal of early stage photochemistry in the light-driven enzyme protochlorophyllide oxidoreductase.

    Directory of Open Access Journals (Sweden)

    Derren J Heyes

    Full Text Available The light-driven enzyme protochlorophyllide oxidoreductase (POR catalyzes the reduction of protochlorophyllide (Pchlide to chlorophyllide (Chlide. This reaction is a key step in the biosynthesis of chlorophyll. Ultrafast photochemical processes within the Pchlide molecule are required for catalysis and previous studies have suggested that a short-lived excited-state species, known as I675*, is the first catalytic intermediate in the reaction and is essential for capturing excitation energy to drive subsequent hydride and proton transfers. The chemical nature of the I675* excited state species and its role in catalysis are not known. Here, we report time-resolved pump-probe spectroscopy measurements to study the involvement of the I675* intermediate in POR photochemistry. We show that I675* is not unique to the POR-catalyzed photoreduction of Pchlide as it is also formed in the absence of the POR enzyme. The I675* species is only produced in samples that contain both Pchlide substrate and Chlide product and its formation is dependent on the pump excitation wavelength. The rate of formation and the quantum yield is maximized in 50∶50 mixtures of the two pigments (Pchlide and Chlide and is caused by direct energy transfer between Pchlide and neighboring Chlide molecules, which is inhibited in the polar solvent methanol. Consequently, we have re-evaluated the mechanism for early stage photochemistry in the light-driven reduction of Pchlide and propose that I675* represents an excited state species formed in Pchlide-Chlide dimers, possibly an excimer. Contrary to previous reports, we conclude that this excited state species has no direct mechanistic relevance to the POR-catalyzed reduction of Pchlide.

  6. Multiple orientations in a physiological complex: the pyruvate-ferredoxin oxidoreductase-ferredoxin system.

    Science.gov (United States)

    Pieulle, Laetitia; Nouailler, Matthieu; Morelli, Xavier; Cavazza, Christine; Gallice, Philippe; Blanchet, Stéphane; Bianco, Pierre; Guerlesquin, Françoise; Hatchikian, E Claude

    2004-12-14

    Ferredoxin I from Desulfovibrio africanus (Da FdI) is a small acidic [4Fe-4S] cluster protein that exchanges electrons with pyruvate-ferredoxin oxidoreductase (PFOR), a key enzyme in the energy metabolism of anaerobes. The thermodynamic properties and the electron transfer between PFOR and either native or mutated FdI have been investigated by microcalorimetry and steady-state kinetics, respectively. The association constant of the PFOR-FdI complex is 3.85 x 10(5) M(-1), and the binding affinity has been found to be highly sensitive to ionic strength, suggesting the involvement of electrostatic forces in formation of the complex. Surprisingly, the punctual or combined neutralizations of carboxylate residues surrounding the [4Fe-4S] cluster slightly affect the PFOR-FdI interaction. Furthermore, hydrophobic residues around the cluster do not seem to be crucial for the PFOR-FdI system activity; however, some of them play an important role in the stability of the FeS cluster. NMR restrained docking associated with site-directed mutagenesis studies suggested the presence of various interacting sites on Da FdI. The modification of additional acidic residues at the interacting interface, generating a FdI pentamutant, evidenced at least two distinct FdI binding sites facing the distal [4Fe-4S] cluster of the PFOR. We also used a set of various small acidic partners to investigate the specificity of PFOR toward redox partners. The remarkable flexibility of the PFOR-FdI system supports the idea that the specificity of the physiological complex has probably been "sacrificed" to improve the turnover rate and thus the efficiency of bacterial electron transfer. PMID:15581360

  7. Synechococcus sp. strain PCC 7002 nifJ mutant lacking pyruvate:ferredoxin oxidoreductase.

    Science.gov (United States)

    McNeely, Kelsey; Xu, Yu; Ananyev, Gennady; Bennette, Nicholas; Bryant, Donald A; Dismukes, G Charles

    2011-04-01

    The nifJ gene codes for pyruvate:ferredoxin oxidoreductase (PFOR), which reduces ferredoxin during fermentative catabolism of pyruvate to acetyl-coenzyme A (acetyl-CoA). A nifJ knockout mutant was constructed that lacks one of two pathways for the oxidation of pyruvate in the cyanobacterium Synechococcus sp. strain PCC 7002. Remarkably, the photoautotrophic growth rate of this mutant increased by 20% relative to the wild-type (WT) rate under conditions of light-dark cycling. This result is attributed to an increase in the quantum yield of photosystem II (PSII) charge separation as measured by photosynthetic electron turnover efficiency determined using fast-repetition-rate fluorometry (F(v)/F(m)). During autofermentation, the excretion of acetate and lactate products by nifJ mutant cells decreased 2-fold and 1.2-fold, respectively. Although nifJ cells displayed higher in vitro hydrogenase activity than WT cells, H(2) production in vivo was 1.3-fold lower than the WT level. Inhibition of acetate-CoA ligase and pyruvate dehydrogenase complex by glycerol eliminated acetate production, with a resulting loss of reductant and a 3-fold decrease in H(2) production by nifJ cells compared to WT cells. Continuous electrochemical detection of dissolved H(2) revealed two temporally resolved phases of H(2) production during autofermentation, a minor first phase and a major second phase. The first phase was attributed to reduction of ferredoxin, because its level decreased 2-fold in nifJ cells. The second phase was attributed to glycolytic NADH production and decreased 20% in nifJ cells. Measurement of the intracellular NADH/NAD(+) ratio revealed that the reductant generated by PFOR contributing to the first phase of H(2) production was not in equilibrium with bulk NADH/NAD(+) and that the second phase corresponded to the equilibrium NADH-mediated process. PMID:21317262

  8. Health risks of alcohol use

    Science.gov (United States)

    Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... Beer, wine, and liquor all contain alcohol. If you are drinking any of these, you are using alcohol. Your drinking patterns may vary, depending on who you are with ...

  9. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Nordestgaard, Børge; Rasmussen, S.;

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white...... men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence......, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1...

  10. Desenvolupament de biosensors amb enzims oxidoreductases basats en transductors amperomètrics modificats químicament

    OpenAIRE

    Prieto Simón, Beatriu

    2006-01-01

    Consultable des del TDX Títol obtingut de la portada digitalitzada La present tesi doctoral recull l'estudi de diverses modificacions químiques de sensors amperomètrics, adreçades cap a cercar solucions per als problemes típicament implícits en el desenvolupament de biosensors basats en enzims oxidoreductases, alhora que es busca la compatibilitat d'aquestes modificacions amb les estratègies d'immobilització enzimàtica emprades. La primera part del treball inclou el desenvolupament de q...

  11. Noncoupled NADH:Ubiquinone Oxidoreductase of Azotobacter vinelandii Is Required for Diazotrophic Growth at High Oxygen Concentrations

    OpenAIRE

    Bertsova, Yulia V.; Alexander V. Bogachev; Skulachev, Vladimir P.

    2001-01-01

    The gene encoding the noncoupled NADH:ubiquinone oxidoreductase (NDH II) from Azotobacter vinelandii was cloned, sequenced, and used to construct an NDH II-deficient mutant strain. Compared to the wild type, this strain showed a marked decrease in respiratory activity. It was unable to grow diazotrophically at high aeration, while it was fully capable of growth at low aeration or in the presence of NH4+. This result suggests that the role of NDH II is as a vital component of the respiratory p...

  12. The structure of Aquifex aeolicus sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration

    OpenAIRE

    Marcia, Marco; Ermler, Ulrich; Peng, Guohong; Michel, Hartmut

    2009-01-01

    Sulfide:quinone oxidoreductase (SQR) is a flavoprotein with homologues in all domains of life except plants. It plays a physiological role both in sulfide detoxification and in energy transduction. We isolated the protein from native membranes of the hyperthermophilic bacterium Aquifex aeolicus, and we determined its X-ray structure in the “as-purified,” substrate-bound, and inhibitor-bound forms at resolutions of 2.3, 2.0, and 2.9 Å, respectively. The structure is composed of 2 Rossmann doma...

  13. Gmca is a putative glucose-methanol-choline oxidoreductase required for the induction of asexual development in aspergillus nidulans

    OpenAIRE

    Oier Etxebeste; Erika Herrero-García; Cortese, Marc S.; Aitor Garzia; Elixabet Oiartzabal-Arano; Vivian de los Ríos; Unai Ugalde; Espeso, Eduardo A.

    2012-01-01

    Aspergillus nidulans asexual differentiation is induced by Upstream Developmental Activators (UDAs) that include the bZIP-type Transcription Factor (TF) FlbB. A 2D-PAGE/MS-MS-coupled screen for proteins differentially expressed in the presence and absence of FlbB identified 18 candidates. Most candidates belong to GO term classes involved in osmotic and/or oxidative stress response. Among these, we focused on GmcA, a putative glucose-methanol-choline oxidoreductase which is upregulated in a Δ...

  14. Chemical constituents from the submerged plant Potamogeton crispus and their effects on NAD(P)H:quinone oxidoreductase 1

    Institute of Scientific and Technical Information of China (English)

    Miao Ye; Jun Zhi Ma; Juan Xiong; Shu Ting Liu; Dong Wang; Chong Gang Yuan; Ji Yan Ma; Jin Feng Hu

    2012-01-01

    A new isopimarane-type diterpene (liwariverol,1) and eight known compounds were isolated and characterized from the EtOAc extract of the whole plant of Potamogeton crispus.The structure of 1 was elucidated to be 17-hydroxy-8αH-isopimara-9(11),15-diene by means of spectroscopic methods.Among the isolates,crenulatoside A (2),an acyclic sesquiterpene glycoside,was found to have anti-oxidative activity with enhancement of the expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) in human neuroblastoma SH-SY5Y cells at 100 μmol/L after a 24-h incubation.

  15. Nurses' Attitudes towards Alcoholics.

    Science.gov (United States)

    Speer, Rita D.

    Nurses' attitudes toward the alcoholic can have a profound impact on the person suffering from alcoholism. These attitudes can affect the alcoholic's care and even whether the alcoholic chooses to recover. This study investigated attitudes of approximately 68 nurses employed in hospitals, 49 nurses in treatment facilities, 58 nursing students, and…

  16. Internet Alcohol Marketing and Underage Alcohol Use

    Science.gov (United States)

    McClure, Auden C.; Tanski, Susanne E.; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D.

    2016-01-01

    BACKGROUND AND OBJECTIVE Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. METHODS A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. RESULTS At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13–2.78 and odds ratio 2.15; 95% confidence interval, 1.06–4.37 respectively) but not with initiation of ever drinking. CONCLUSIONS Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. PMID:26738886

  17. Effects of 5-azacytidine and methyl-group deficiency on NAD(P)H: quinone oxidoreductase and glutathione S-transferase in liver.

    Science.gov (United States)

    Wagner, G; Pott, U; Bruckschen, M; Sies, H

    1988-01-01

    Treatment with 5-azacytidine or dietary methyl-group deficiency effected DNA hypomethylation in mouse liver. With these treatments, NAD(P)H: quinone oxidoreductase (EC 1.6.99.2) and some glutathione S-transferase (EC 2.5.1.18) activities were over-expressed, lactate dehydrogenase (EC 1.1.1.27) activity was unaffected and the level of cytochrome P-450 was decreased. The 5-azacytidine induction of NAD(P)H: quinone oxidoreductase was significantly suppressed by puromycin, suggesting that increased enzyme activity results from an elevated level of enzyme-protein synthesis. Regulation at the transcriptional level was revealed by a substantial increase in mRNA of NAD(P)H: quinone oxidoreductase, as shown by Northern-blot analysis. The enzyme pattern observed with 5-azacytidine and with the (carcinogenic) dietary methyl-group deficiency resembles that found in hepatic nodules. Images Fig. 3. PMID:2458098

  18. [Alcohol and arrhythmias].

    Science.gov (United States)

    Pfeiffer, D; Jurisch, D; Neef, M; Hagendorff, A

    2016-09-01

    The effects of alcohol on induction of arrhythmias is dose-dependent, independent of preexisting cardiovascular diseases or heart failure and can affect otherwise healthy subjects. While the probability of atrial fibrillation increases with the alcohol dosage, events of sudden cardiac death are less frequent with low and moderate consumption but occur more often in heavy drinkers with alcoholic cardiomyopathy. Men are first affected at higher dosages of alcohol but women can suffer from arrhythmias at lower dosages. Thromboembolisms and ischemic stroke can occur less often at lower dosages of alcohol; however, hemorrhagic stroke and subarachnoid hemorrhage are increased with higher alcohol dosages. Recognizable protective mechanisms of alcohol with respect to cardiovascular diseases only occur with lower amounts of alcohol of less than 10 g per day. Underlying mechanisms explain these controversial effects. Specific therapeutic options for alcohol-related arrhythmias apart from abstinence from alcohol consumption are not known. PMID:27582366

  19. Alcohol and Breastfeeding

    DEFF Research Database (Denmark)

    Haastrup, Maija Bruun; Pottegård, Anton; Damkier, Per

    2014-01-01

    While the harmful effects of alcohol during pregnancy are well-established, the consequences of alcohol intake during lactation have been far less examined. We reviewed available data on the prevalence of alcohol intake during lactation, the influence of alcohol on breastfeeding......, the pharmacokinetics of alcohol in lactating women and nursing infants and the effects of alcohol intake on nursing infants. A systematic search was performed in PubMed from origin to May 2013, and 41 publications were included in the review. Approximately half of all lactating women in Western countries consume...... alcohol while breastfeeding. Alcohol intake inhibits the milk ejection reflex, causing a temporary decrease in milk yield. The alcohol concentrations in breast milk closely resemble those in maternal blood. The amount of alcohol presented to nursing infants through breast milk is approximately 5...

  20. Differential Regulation of Duplicate Light-Dependent Protochlorophyllide Oxidoreductases in the Diatom Phaeodactylum tricornutum.

    Directory of Open Access Journals (Sweden)

    Heather M Hunsperger

    Full Text Available Diatoms (Bacilliariophyceae encode two light-dependent protochlorophyllide oxidoreductases (POR1 and POR2 that catalyze the penultimate step of chlorophyll biosynthesis in the light. Algae live in dynamic environments whose changing light levels induce photoacclimative metabolic shifts, including altered cellular chlorophyll levels. We hypothesized that the two POR proteins may be differentially adaptive under varying light conditions. Using the diatom Phaeodactylum tricornutum as a test system, differences in POR protein abundance and por gene expression were examined when this organism was grown on an alternating light:dark cycles at different irradiances; exposed to continuous light; and challenged by a significant decrease in light availability.For cultures maintained on a 12h light: 12h dark photoperiod at 200μE m-2 s-1 (200L/D, both por genes were up-regulated during the light and down-regulated in the dark, though por1 transcript abundance rose and fell earlier than that of por2. Little concordance occurred between por1 mRNA and POR1 protein abundance. In contrast, por2 mRNA and POR2 protein abundances followed similar diurnal patterns. When 200L/D P. tricornutum cultures were transferred to continuous light (200L/L, the diurnal regulatory pattern of por1 mRNA abundance but not of por2 was disrupted, and POR1 but not POR2 protein abundance dropped steeply. Under 1200μE m-2 s-1 (1200L/D, both por1 mRNA and POR1 protein abundance displayed diurnal oscillations. A compromised diel por2 mRNA response under 1200L/D did not impact the oscillation in POR2 abundance. When cells grown at 1200L/D were then shifted to 50μE m-2 s-1 (50L/D, por1 and por2 mRNA levels decreased swiftly but briefly upon light reduction. Thereafter, POR1 but not POR2 protein levels rose significantly in response to this light stepdown.Given the sensitivity of diatom por1/POR1 to real-time light cues and adherence of por2/POR2 regulation to the diurnal cycle, we suggest

  1. Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production

    Directory of Open Access Journals (Sweden)

    Uesaka Miki

    2008-12-01

    Full Text Available Abstract Background P450 oxidoreductase (POR catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS, and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis. Methods Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcription-polymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells. Results POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for aromatase. Transient expression of POR in COS-7 cells, which expressed a constant amount of aromatase protein, greatly increased the rate of conversion of androstenedione to estrone, in a dose-dependent manner. The expression of mutant POR proteins (R457H or V492E, such as those found in ABS patients, had much less effect on aromatase activity than expression of wild

  2. Enhanced activity of yqhD oxidoreductase in synthesis of 1,3-propanediol by error-prone PCR

    Institute of Scientific and Technical Information of China (English)

    Hongmei Li; Jia Chen; Yinghua Li

    2008-01-01

    yqhD oxidoreductase was determined to be an NADP-dependent dehydrogenase,and was more active toward 3-HPA when compared to 1,3-propanediol oxidoreductase.To further improve enzyme activity towards 3-hydroxypropionaldehyde (3-HPA),error-prone PCR was implemented to mutant yqhD gene.Two mutants,D99QN147H and Q202A with increased catalytic and affinity efficiency,were obtained after one round of error-prone polymerase chain reaction.And the catalytic efficiency of the mutant D99QN147H was up to 4-fold greater than the wild enzyme (0.0375 min-1 mM-1 vs.0.0078 min-1 mM-1).The recombined strain containing pET28yqhD D99QNI47H yielded 28 g L-1 of 1,3-propanediol in the fed-batch LB cultures (1 L volume) with an initial 3-HPA concentration of 40 g L-1,which was higher than the 21 and 17 g L-1 of 1,3-propanediol from the mutant Q202A and the wild-type,respectively.Except for propionaldehyde,the optimal mutant D99QN147H also exhibited higher activity on a range of substituted aldehydes than the wild-type.

  3. Genetic polymorphism of N-acetyltransferases, glutathione S-transferase M1 and NAD(P)H:quinone oxidoreductase in relation to malignant and benign pancreatic disease risk. The International Pancreatic Disease Study Group.

    Science.gov (United States)

    Bartsch, H; Malaveille, C; Lowenfels, A B; Maisonneuve, P; Hautefeuille, A; Boyle, P

    1998-06-01

    Carcinogens present in cigarette smoke and diet have been associated with pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative agents and that therefore genetic variation in enzymes metabolizing these carcinogens could modify the risk of developing malignant and benign pancreatic disease. The effect of the genetic polymorphism of acetyltransferases (NAT1) and NAT2), glutathione S-transferase M1 (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic diseases (cancer, pancreatitis) was examined in a case-control study. PCR-based assays were used for genotype analysis of genomic DNA from whole blood cells. Samples collected from Caucasian patients with diagnosed pancreatic cancer (n = 81), with non-alcoholic (n = 41) and alcoholic pancreatitis (n = 73) and from asymptomatic control subjects (n = 78) were analysed. The prevalence of GSTM1 null genotype and of NAT2 fast and slow acetylator genotypes and the distribution of frequencies for NQO1 genotypes did not differ in subjects with pancreatic diseases vs controls. For NAT1 slow acetylators a non-significant excess (P = 0.18) was found among pancreatic cancer cases vs controls. There was a significant over-representation of the GSTM1 AB or B genotype in all pancreatic disease cases combined (OR = 2.6; P < 0.05). When concurrent controls were pooled with literature controls (n = 1427), OR was 1.4 (P = 0.08). The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic diseases. PMID:9696930

  4. The activity of uridine diphosphate-D-glucose: Nicotinamide-adenine dinucleotide oxidoreductase in cambial tissue and differentiating xylem isolated from sycamore trees.

    Science.gov (United States)

    Rubery, P H

    1972-06-01

    The activity of UDPGlc: NAD oxidoreductase is measured in enzyme preparations obtained from sycamore cambium and xylem tissue. The activity of this enzyme is greater in xylem than in cambium whether expressed on a specific activity basis or on a per-cell basis. It is suggested that, in developing xylem, direct oxidation of UDPGlc may contribute significantly to the biosynthesis of polysaccharide precursors.

  5. The reaction of NADPH with bovine mitochondrial NADH:ubiquinone oxidoreductase revisited: II. Comparison of the proposed working hypothesis with literature data.

    NARCIS (Netherlands)

    S.P.J. Albracht

    2010-01-01

    The first purification of bovine NADH:ubiquinone oxidoreductase (Complex I) was reported nearly half a century ago (Hatefi et al. J Biol Chem 237:1676-1680, 1962). The pathway of electron-transfer through the enzyme is still under debate. A major obstacle is the assignment of EPR signals to the indi

  6. Laboratory Prototype of Bioreactor for Oxidation of Toxic D-Lactate Using Yeast Cells Overproducing D-Lactate Cytochrome c Oxidoreductase.

    Science.gov (United States)

    Karkovska, Maria; Smutok, Oleh; Gonchar, Mykhailo

    2016-01-01

    D-lactate is a natural component of many fermented foods like yogurts, sour milk, cheeses, and pickles vegetable products. D-lactate in high concentrations is toxic for children and people with short bowel syndrome and provokes encephalopathy. These facts convincingly demonstrate a need for effective tools for the D-lactate removal from some food products. The main idea of investigation is focused on application of recombinant thermotolerant methylotrophic yeast Hansenula polymorpha "tr6," overproducing D-lactate: cytochrome c oxidoreductase (EC 1.1.2.4, D-lactate cytochrome c oxidoreductase, D-lactate dehydrogenase (cytochrome), DLDH). In addition to 6-fold overexpression of DLDH under a strong constitutive promoter (prAOX), the strain of H. polymorpha "tr6" (gcr1 catX/Δcyb2, prAOX_DLDH) is characterized by impairment in glucose repression of AOX promoter, devoid of catalase and L-lactate-cytochrome c oxidoreductase activities. Overexpression of DLDH coupling with the deletion of L-lactate-cytochrome c oxidoreductase activity opens possibility for usage of the strain as a base for construction of bioreactor for removing D-lactate from fermented products due to oxidation to nontoxic pyruvate. A laboratory prototype of column-type bioreactor for removing a toxic D-lactate from model solution based on permeabilized cells of the H. polymorpha "tr6" and alginate gel was constructed and efficiency of this process was tested. PMID:27446952

  7. Laboratory Prototype of Bioreactor for Oxidation of Toxic D-Lactate Using Yeast Cells Overproducing D-Lactate Cytochrome c Oxidoreductase

    Directory of Open Access Journals (Sweden)

    Maria Karkovska

    2016-01-01

    Full Text Available D-lactate is a natural component of many fermented foods like yogurts, sour milk, cheeses, and pickles vegetable products. D-lactate in high concentrations is toxic for children and people with short bowel syndrome and provokes encephalopathy. These facts convincingly demonstrate a need for effective tools for the D-lactate removal from some food products. The main idea of investigation is focused on application of recombinant thermotolerant methylotrophic yeast Hansenula polymorpha “tr6,” overproducing D-lactate: cytochrome c oxidoreductase (EC 1.1.2.4, D-lactate cytochrome c oxidoreductase, D-lactate dehydrogenase (cytochrome, DLDH. In addition to 6-fold overexpression of DLDH under a strong constitutive promoter (prAOX, the strain of H. polymorpha “tr6” (gcr1 catX/Δcyb2, prAOX_DLDH is characterized by impairment in glucose repression of AOX promoter, devoid of catalase and L-lactate-cytochrome c oxidoreductase activities. Overexpression of DLDH coupling with the deletion of L-lactate-cytochrome c oxidoreductase activity opens possibility for usage of the strain as a base for construction of bioreactor for removing D-lactate from fermented products due to oxidation to nontoxic pyruvate. A laboratory prototype of column-type bioreactor for removing a toxic D-lactate from model solution based on permeabilized cells of the H. polymorpha “tr6” and alginate gel was constructed and efficiency of this process was tested.

  8. Alcohol homograph priming in alcohol-dependent inpatients

    NARCIS (Netherlands)

    Woud, M.L.; Salemink, E.; Gladwin, T.E.; Wiers, R.W.H.J.; Becker, E.S.; Lindenmeyer, J.; Rinck, M.

    2016-01-01

    Aim: Alcohol dependency is characterized by alcohol-related interpretation biases (IBs): Individuals with high levels of alcohol consumption generate more alcohol-related than alcohol-unrelated interpretations in response to ambiguous alcohol-related cues. However, a response bias could be an altern

  9. Alcohol Use and Older Adults

    Science.gov (United States)

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  10. Alcohol: A Women's Health Issue

    Science.gov (United States)

    ... itself can cause serious long-term health consequences. Alcohol in Women’s Lives: Safe Drinking Over a Lifetime ... much, and how often to drink. What Are Alcohol Abuse and Alcoholism? Alcohol abuse is a pattern ...

  11. Women and Alcohol

    Science.gov (United States)

    ... turn JavaScript on. Feature: Rethinking Drinking Women and Alcohol Past Issues / Spring 2014 Table of Contents Women react differently than men to alcohol and face higher risks from it. Pound for ...

  12. Alcohol and Cancer Risk

    Science.gov (United States)

    ... Overview Cancer Prevention Overview–for health professionals Research Alcohol and Cancer Risk On This Page What is ... in the risk of colorectal cancer. Research on alcohol consumption and other cancers: Numerous studies have examined ...

  13. Alcohol and Migraine

    Science.gov (United States)

    ... on Pinterest Follow us on Instagram DONATE TODAY Alcohol and Migraine Abuse, Maltreatment, and PTSD and Their ... to Migraine Altitude, Acute Mountain Sickness and Headache Alcohol and Migraine Anxiety and Depression Caffeine and Migraine ...

  14. Benzyl Alcohol Topical

    Science.gov (United States)

    Benzyl alcohol lotion is used to treat head lice (small insects that attach themselves to the skin) in adults ... children less than 6 months of age. Benzyl alcohol is in a class of medications called pediculicides. ...

  15. Fetal Alcohol Exposure

    Science.gov (United States)

    ... a woman drinks while pregnant. Alcohol can disrupt fetal development at any stage during a pregnancy—including at ... Clinical Diagnoses IOM Diagnoses Fetal Alcohol Syndrome ... pregnancy can disrupt normal development of the face and the brain. In fact, ...

  16. Children of alcoholics

    Directory of Open Access Journals (Sweden)

    Robert Oravecz

    2002-09-01

    Full Text Available The author briefly interprets the research – results, referring to the phenomenon of children of alcoholics, especially the psychological and psychopathological characteristics of children of alcoholics in adolescence and young adulthood. The author presents a screening study of adolescents. The sample contains 200 high school students at age 18. The aim of the survey was to discover the relationship between alcohol consumption of parents, PTSD - related psychopathological symptoms and reported life quality of their children. The study confirmed the hypothesis about a substantial correlation between high alcohol consumption of parents, higher psychopathological symptom - expression and lower reported life quality score of their children. Higher PTSD-related symptomatology in children of alcoholics is probably resulted by home violence, which is very often present in family of alcoholics. The article also evaluated the results regarding suicide ideation of children of alcoholics, which is definitely more frequent and more intense than in their peers living in non alcohol – dependent families.

  17. Alcohol Alert: Link Between Stress and Alcohol

    Science.gov (United States)

    ... Hodgkinson, C.A.; Yuan, Q.; et al. The influence of GABrA2, childhood trauma, and their interaction on alcohol, heroin, and ... Articles examine different sources of stress, such as childhood abuse and ... stress influences the development of alcohol abuse and dependence, and ...

  18. Alcohol and Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Gao Yinglan; Song Jingyu; Jin Junshuo; Zhong Xiuhong; Ren Xiangshan; Liu Shuangping

    2005-01-01

    Objectives To study the relationship between alcohol and atherosclerosis (AS).Methods The paper reviewed the mechanism of the alcohol leading to AS from four aspects such as the introduction of alcohol and AS, imbalance of oxidationantioxidation system, oxygen free radical (OFR) and endothelium cell (EC) apoptosis, apoptosis and AS.Results Excessive alcohol could lead to imbalance of oxidation-antioxidation system, and increase OFR, in the meanwhile, OFR could lead to EC apoptosis,which could lead to AS.

  19. The Alcoholism Questionnaire.

    Science.gov (United States)

    Ferneau, E.; Mueller, S.

    The alcoholism questionnaire used to survey college student attitudes on the subject is provided. It is identical to the drug-abuse questionnaire except for word changes appropriate to the subject matter. The questionnaire consists of 40 statements about alcoholics and alcoholism, with 7 possible responses: (1) completely disagree; (2) mostly…

  20. Alcoholism and Lesbians

    Science.gov (United States)

    Gedro, Julie

    2014-01-01

    This chapter explores the issues involved in the relationship between lesbianism and alcoholism. It examines the constellation of health and related problems created by alcoholism, and it critically interrogates the societal factors that contribute to the disproportionately high rates of alcoholism among lesbians by exploring the antecedents and…

  1. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna

    2009-01-01

    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  2. Television: Alcohol's Vast Adland.

    Science.gov (United States)

    2002

    Concern about how much television alcohol advertising reaches underage youth and how the advertising influences their attitudes and decisions about alcohol use has been widespread for many years. Lacking in the policy debate has been solid, reliable information about the extent of youth exposure to television alcohol advertising. To address this…

  3. Alcohol and Minority Youth.

    Science.gov (United States)

    Wright, Roosevelt, Jr.; Watts, Thomas D.

    1991-01-01

    Maintains that minority youth who use (or abuse) alcohol in American society deal with using alcohol, being minority, and being young, three dimensions viewed by society with mixed, sometimes hostile and/or fearful reactions. Suggests that examining alcoholism among minority youth involves coming to grips with poverty, education, income, and life…

  4. Application of L-lactate-cytochrome c-oxidoreductase for development of amperometric biosensor for L-lactate determination

    Directory of Open Access Journals (Sweden)

    Dzyadevych S. V.

    2009-06-01

    Full Text Available Aim. Development of amperometric biosensor based on L-lactate-cytochrome c-oxidoreductase (flavocytochrome b2, FC b2 for lactate determination. Methods. All experiments were performed using the amperometric method of detection. The methods of electrochemical polymerization and immobilization in glutaraldehyde vapors were used for FC b2 immobilization on the surface of electrodes. Results. The FC b2 preparation, which demonstrated the best operational characteristics after immobilization in poly (3,4-ethylen dioxythiophene, was selected. The selectivity, operational and storage stability, and pH-optimum for operation of the created biosensor were determined. The analysis of L-lactate in the model solutions and wine samples was carried outusing the developed biosensor. Conclusion. The FC b2-based biosensor due to its high stability can be effectively used for lactate determination in blood and other liquids containing no ethanol. After the selectivity optimization, the devise can be also applied for wine analysis.

  5. Purification and characterization of sulfide:quinone oxidoreductase from an acidophilic iron-oxidizing bacterium, Acidithiobacillus ferrooxidans.

    Science.gov (United States)

    Wakai, Satoshi; Tsujita, Mizuho; Kikumoto, Mei; Manchur, Mohammed A; Kanao, Tadayoshi; Kamimura, Kazuo

    2007-11-01

    Sulfide:quinone oxidoreductase (SQR) was purified from membrane of acidophilic chemolithotrophic bacterium Acidithiobacillus ferrooxidans NASF-1 cells grown on sulfur medium. It was composed of a single polypeptide with an apparent molecular mass of 47 kDa. The apparent K(m) values for sulfide and ubiquinone were 42 and 14 muM respectively. The apparent optimum pH for the SQR activity was about 7.0. A gene encoding a putative SQR of A. ferrooxidans NASF-1 was cloned and sequenced. The gene was expressed in Escherichia coli as a thioredoxin-fusion protein in inclusion bodies in an inactive form. A polyclonal antibody prepared against the recombinant protein reacted immunologically with the purified SQR. Western blotting analysis using the antibody revealed an increased level of SQR synthesis in sulfur-grown A. ferrooxidans NASF-1 cells, implying the involvement of SQR in elemental sulfur oxidation in sulfur-grown A. ferrooxidans NASF-1 cells. PMID:17986789

  6. Mechanism of porcine liver xanthine oxidoreductase mediated N-oxide reduction of cyadox as revealed by docking and mutagenesis studies.

    Directory of Open Access Journals (Sweden)

    Chigang Chen

    Full Text Available Xanthine oxidoreductase (XOR is a cytoplasmic molybdenum-containing oxidoreductase, catalyzing both endogenous purines and exogenous compounds. It is suggested that XOR in porcine hepatocytes catalyzes the N-oxide reduction of quinoxaline 1,4-di-N-oxides (QdNOs. To elucidate the molecular mechanism underlying this metabolism, the cDNA of porcine XOR was cloned and heterologously expressed in Spodoptera frugiperda insect cells. The bovine XOR, showing sequence identity of 91% to porcine XOR, was employed as template for homology modeling. By docking cyadox, a representative compound of QdNOs, into porcine XOR model, eight amino acid residues, Gly47, Asn352, Ser360, Arg427, Asp430, Asp431, Ser1227 and Lys1230, were located at distances of less than 4Å to cyadox. Site-directed mutagenesis was performed to analyze their catalytic functions. Compared with wild type porcine XOR, G47A, S360P, D431A, S1227A, and K1230A displayed altered kinetic parameters in cyadox reduction, similarly to that in xanthine oxidation, indicating these mutations influenced electron-donating process of xanthine before subsequent electron transfer to cyadox to fulfill the N-oxide reduction. Differently, R427E and D430H, both located in the 424-434 loop, exhibited a much lower K(m and a decreased V(max respectively in cyadox reduction. Arg427 may be related to the substrate binding of porcine XOR to cyadox, and Asp430 is suggested to be involved in the transfer of electron to cyadox. This study initially reveals the possible catalytic mechanism of porcine XOR in cyadox metabolism, providing with novel insights into the structure-function relationship of XOR in the reduction of exogenous di-N-oxides.

  7. Inhibitory Effects of Tart Cherry (Prunus cerasus) Juice on Xanthine Oxidoreductase Activity and its Hypouricemic and Antioxidant Effects on Rats.

    Science.gov (United States)

    Haidari, F; Mohammad Shahi, M; Keshavarz, S A; Rashidi, M R

    2009-03-01

    The aim of this study was to investigate the effect of tart cherry juice on serum uric acid levels, hepatic xanthine oxidoreductase activity and two non-invasive biomarkers of oxidative stress (total antioxidant capacity and malondialdehyde concentration), in normal and hyperuricemic rats. Tart cherry juice (5 ml/kg) was given by oral gavage to rats for 2 weeks. Allopurinol (5 mg/kg) was used as a positive control and was also given by oral gavage. Data showed that tart cherry juice treatment did not cause any significant reduction in the serum uric acid levels in normal rats, but significantly reduced (P<0.05) the serum uric acid levels of hyperuricemic rats in a time-dependent manner. Tart cherry juice treatment also inhibited hepatic xanthine oxidase/dehydrogenase activity. Moreover, a significant increase (P<0.05) in serum total antioxidant capacity was observed in tart cherry juice treated-rats in both normal and hyperuricemic groups. The oral administration of tart cherry juice also led to a significant reduction (P<0.05) in MDA concentration in the hyperuricemic rats. Although the hypouricemic effect of allopurinol, as a putative inhibitor of xanthine oxidoreductase, was much higher than that of tart cherry, it could not significantly change anti-oxidative parameters. These features of tart cherry make it an attractive candidate for the prophylactic treatment of hyperuricaemia, particularly if it is to be taken on a long-term basis. Further investigations to define its clinical efficacy would be highly desirable. PMID:22691805

  8. Structural determinants of stereospecificity in yeast alcohol dehydrogenase.

    Science.gov (United States)

    Weinhold, E G; Glasfeld, A; Ellington, A D; Benner, S A

    1991-10-01

    Replacing Leu-182 by Ala in yeast alcohol dehydrogenase (YADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) yields a mutant that retains 34% of its kcat value and makes one stereochemical "mistake" every 850,000 turnovers (instead of approximately 1 error every 7,000,000,000 turnovers in native YADH) in its selection of the 4-Re hydrogen of NADH. Half of the decrease in stereochemical fidelity comes from an increase in the rate of transfer of the 4-Si hydrogen of NADH. The mutant also accepts 5-methylnicotinamide adenine dinucleotide, a cofactor analog not accepted by native YADH. The stereospecificity of the mutant is lower still with analogs of NADH where the carboxamide group of the nicotinamide ring is replaced by groups with weaker hydrogen bonding potential. For example, with thio-NADH, the mutant enzyme makes 1 stereochemical "mistake" every 450 turnovers. Finally, the double mutant T157S/L182A, in which Thr-157 is replaced by Ser and Leu-182 is replaced by Ala, also shows decreased stereochemical fidelity. These results suggest that Si transfer in the mutant enzymes arises from NADH bound in a syn conformation in the active site and that this binding is not obstructed in native YADH by side chains essential for catalysis.

  9. Alcohol and atherosclerosis

    DEFF Research Database (Denmark)

    Tolstrup, Janne; Grønbaek, Morten

    2007-01-01

    (CHD). The cardioprotective effect of alcohol seems to be larger among middle-aged and elderly adults than among young adults, who do not have a net beneficial effect of a light to moderate alcohol intake in terms of reduced all-cause mortality. The levels of alcohol at which the risk of CHD is lowest......Light to moderate alcohol intake is known to have cardioprotective properties; however, the magnitude of protection depends on other factors and may be confined to some subsets of the population. This review focuses on factors that modify the relationship between alcohol and coronary heart disease...... and the levels of alcohol at which the risk of CHD exceeds the risk among abstainers are lower for women than for men. The pattern of drinking seems important for the apparent cardioprotective effect of alcohol, and the risk of CHD is generally lower for steady versus binge drinking. Finally, there is some...

  10. Alcohol disrupts sleep homeostasis.

    Science.gov (United States)

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  11. National Institute on Alcohol Abuse and Alcoholism

    Science.gov (United States)

    ... day 12 hours ago Areas of Interest Scientists & Researchers Certificates of Confidentiality Data and Safety Monitoring Guidelines NIAAA-Funded Research Centers Clinicians Helping Patients Who Drink Too Much Alcohol Screening and Brief Intervention for Youth Clinical Trials ...

  12. Alcohol Advertising and Alcohol Consumption by Adolescents

    OpenAIRE

    Henry Saffer; Dhaval Dave

    2003-01-01

    The purpose of this paper is to empirically estimate the effects of alcohol advertising on adolescent alcohol consumption. The theory of brand capital is used to explain the effects of advertising on consumption. The industry response function and the evidence from prior studies indicate that the empirical strategy should maximize the variance in the advertising data. The approach in this paper to maximizing the variance in advertising data is to employ cross sectional data. The Monitoring th...

  13. Alcohol Expectancies in Young Adult Sons of Alcoholics and Controls.

    Science.gov (United States)

    Brown, Sandra A.; And Others

    Adolescent offspring of alcoholics have been found to have higher alcohol reinforcement expectancies than do teenagers from nonalcoholic families. In particular, those with a positive family history of alcoholism expect more cognitive and motor enhancement with alcohol consumption. This study examined the alcohol expectancies of 58 matched pairs…

  14. [Alcohol and nutrition].

    Science.gov (United States)

    Maillot, F; Farad, S; Lamisse, F

    2001-11-01

    Alcoholism and alcohol-associated organ injury is one of the major health problems worldwide. Alcohol may lead to an alteration in intermediary metabolism and the relation between alcohol intake and body weight is a paradox. The effect of alcohol intake on resting metabolic rate, assessed by indirect calorimetry, and lipid oxidation, is still controversial. Small quantities of ethanol seem to have no effect on body weight. Ingestion of moderate amounts may lead to an increase in body weight, via a lipid-oxidizing suppressive effect. Chronic intake of excessive amounts in alcoholics leads to a decrease in body weight, probably via increased lipid oxidation and energy expenditure. Chronic ethanol abuse alters lipid-soluble (vitamins A, D and E) and water-soluble (B-complex vitamins, vitamin C) vitamins status, and some trace elements status such as magnesium, selenium or zinc.

  15. Alcohol in moderation

    DEFF Research Database (Denmark)

    Mueller, Simone; Lockshin, Larry; Louviere, Jordan J.

    2011-01-01

    Purpose: The study examines the market potential for low and very low alcohol wine products under two different tax regimes. The penetration and market share of low alcohol wine are estimated under both tax conditions. Consumers’ alcoholic beverage purchase portfolios are analysed and those...... products identified, which are jointly purchased with low alcohol wines. The effect of a tax increase on substitution patterns between alcoholic beverages is examined. Methodology: In a discrete choice experiment, based on their last purchase, consumers select one or several different alcoholic beverages...... into a purchase basket. An experimental design controlled the beverages’ price variation. Applying an intra-individual research design, respondents’ purchases were simulated under current and increased taxes. Findings: A market potential for low and very low wine products of up to ten percent of the wine market...

  16. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Murilo Foppa

    2001-02-01

    Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

  17. Fetal Alcohol Spectrum Disorders

    OpenAIRE

    Warren, Kenneth R.; Hewitt, Brenda G.; Thomas, Jennifer D.

    2010-01-01

    The adverse effects of prenatal alcohol consumption have long been known; however, a formal description and clinical diagnosis of these effects was not introduced until 1973. Since then, the distinction of the wide range of effects that can be induced by prenatal alcohol exposure, and, consequently, the terminology to describe these effects has continued to evolve. Although much progress has been made in understanding the consequences of prenatal alcohol exposure, challenges still remain in p...

  18. Children of alcoholics

    OpenAIRE

    Robert Oravecz

    2002-01-01

    The author briefly interprets the research – results, referring to the phenomenon of children of alcoholics, especially the psychological and psychopathological characteristics of children of alcoholics in adolescence and young adulthood. The author presents a screening study of adolescents. The sample contains 200 high school students at age 18. The aim of the survey was to discover the relationship between alcohol consumption of parents, PTSD - related psychopathological symptoms and ...

  19. Alcohol-Induced Blackout

    Directory of Open Access Journals (Sweden)

    Dai Jin Kim

    2009-11-01

    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  20. ADOLESCENTS AND ALCOHOL

    OpenAIRE

    SPEAR, LINDA PATIA

    2013-01-01

    The high levels of alcohol consumption characteristic of adolescence may be in part biologically based, given that elevated consumption levels are also evident during this developmental transition in other mammalian species as well. Studies conducted using a simple animal model of adolescence in the rat has shown adolescents to be more sensitive than adults to social facilitatory and rewarding effects of alcohol, but less sensitive to numerous alcohol effects that may serve as cues to limit i...

  1. Affordability of alcohol and alcohol-related mortality in Belarus.

    Science.gov (United States)

    Razvodovsky, Yury E

    2013-01-01

    Alcohol abuse has numerous adverse health and social consequences. The consumer response to changes in alcohol affordability is an important issue on alcohol policy debates. Studies from many countries have shown an inverse relationship between alcohol prices and alcohol consumption in the population. There are, however, suggestions that increasing the price of alcohol by rising taxes may have limited effect on alcohol-related problems, associated with long-term heavy drinking. The aim of the present study was to evaluate the relationship between alcohol affordability and alcohol-related mortality rates in post-Soviet Belarus. For this purpose trends in alcohol-related mortality rates (mortality from liver cirrhosis, pancreatitis, alcoholism and alcohol psychoses) and affordability of vodka between 1990 and 2010 were compared. The time series analysis revealed that 1% increase in vodka affordability is associated with an increase in liver cirrhosis mortality of 0,77%, an increase in pancreatitis mortality of 0.53%, an increase in mortality from alcoholism and alcohol psychoses of 0,70%. The major conclusion emerging from this study is that affordability of alcohol is one of the most important predictor of alcohol-related problems in a population. These findings provide additional evidence that decreasing in affordability of alcohol is an effective strategy for reducing alcohol consumption and alcohol-related harm.

  2. Recovery of ascorbic oxidoreductase from crude extract with an aqueous two-phase system in a perforated rotating disc contactor

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Figueiredo Porto

    2004-09-01

    Full Text Available A continuous perforated rotating disc contactor was used to extract the enzyme ascorbic oxidoreductase (E.C.1.10.3.3 from crude extract of Curcubita maxima with an aqueous two-phase system of poly (ethylene glycol and phosphate salts. The effect of dispersed phase velocity on either protein mass transfer coefficients or separation efficiency at 1, 2 and 3 mL/min was studied. An increase of the mass transfer coefficients was observed with the dispersed phase velocity, while the separation efficiency showed a small decrease with the increase of this parameter. The experimental results obtained during continuous extraction showed that the ascorbic oxidoreductase activity was partitioned preferentially into the salt-rich phase in all conditions studied. The best recovery of enzyme activity was 236%, with a purification factor of 34 in flow rates of 1 mL/min for dispersed phase.Uma coluna de discos perfurados rotativos foi utilizada na extração da enzima ascorbato oxidorredutase (E.C.1.10.3.3, obtida do extrato bruto de Curcubita maxima, através da utilização do sistema bifásico aquoso Polietilenoglicol-sais de fosfato. Os efeitos da velocidade da fase dispersa nos coeficientes de transferência de massa e na eficiência de separação para valores de 1, 2 e 3 mL/min foram estudados. Observou-se um aumento da transferência de massa com a velocidade da fase dispersa, enquanto que a eficiência de separação demonstrou uma ligeira redução com o aumento deste parâmetro. Os resultados experimentais obtidos durante a extração contínua demonstraram que a atividade da ascorbato oxidorredutase se concentrou preferencialmente na fase rica em sal para todas as condições estudadas. A maior recuperação da atividade enzimática foi de 236%, com um fator de purificação de 34 para o valor de 1 mL/min para a fase dispersa.

  3. Characterization of Saccharomyces cerevisiae CYP51 and a CYP51 fusion protein with NADPH cytochrome P-450 oxidoreductase expressed in Escherichia coli.

    OpenAIRE

    Venkateswarlu, K; Kelly, D. E.; Kelly, S. L.

    1997-01-01

    Saccharomyces cerevisiae CYP51, target of azole antifungal agents, and CYP51 fused with S. cerevisiae cytochrome P-450 oxidoreductase (FUS protein) were expressed in active forms in Escherichia coli by cloning into pET15b. The expression was monitored immunologically, catalytically, and by using reduced carbon monoxide difference and type II binding spectra. CYP51 and FUS enzymes were located in membranes and produced a Soret peak at 448 nm in the reduced CO difference spectrum. The cytochrom...

  4. FastStats: Alcohol Use

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Alcohol Use Recommend on Facebook Tweet Share Compartir Data ... alcoholic liver disease deaths: 18,146 Number of alcohol-induced deaths, excluding accidents and homicides: 29,001 ...

  5. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  6. Alcoholism and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Soo-Jeong Kim

    2012-04-01

    Full Text Available Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM, which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

  7. Fetal Alcohol Spectrum Disorder

    Science.gov (United States)

    Caley, Linda M.; Kramer, Charlotte; Robinson, Luther K.

    2005-01-01

    Fetal alcohol spectrum disorder (FASD) is a serious and widespread problem in this country. Positioned within the community with links to children, families, and healthcare systems, school nurses are a critical element in the prevention and treatment of those affected by fetal alcohol spectrum disorder. Although most school nurses are familiar…

  8. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    DA LUZ PROTASIO L.

    2001-01-01

    Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

  9. Alcohol on wheels.

    Science.gov (United States)

    McDermott, F T

    1986-01-01

    Alcohol misuse remains the single most important contributing factor to road accident deaths and injuries in Australia. The results of compulsory blood alcohol tests on road casualties have shown that probationary licensed drivers have a threefold increased risk of road accident injury compared to fully licensed drivers and are additionally over-represented in alcohol-related crashes. These findings led the Victorian Road Trauma Committee to campaign for a zero blood alcohol limit for learner and probationary drivers and motorcyclists. In May 1984, zero blood alcohol legislation was enacted in Victoria. The present legislation applies to learner and first year probationary licence holders. For the first time we have evidence of a moderate reduction in alcohol-related road trauma in Victoria. Between 1977 and 1983 there has been a significant reduction in the proportion of driver casualties admitted to hospital with illegal blood alcohol concentrations and in the number of driver fatalities with blood alcohol concentrations in excess of 0.15 g%. An evaluation of the following recommended drink driver countermeasures is presented: improved driver education, increased penalties, re-education--rehabilitation programmes for convicted drink drivers, interlock devices and an increase in the legal drinking age. PMID:3461765

  10. Rational proteomics I. Fingerprint identification and cofactor specificity in the short-chain oxidoreductase (SCOR) enzyme family.

    Science.gov (United States)

    Duax, William L; Pletnev, Vladimir; Addlagatta, Anthony; Bruenn, Jeremy; Weeks, Charles M

    2003-12-01

    The short-chain oxidoreductase (SCOR) family of enzymes includes over 2000 members identified in sequenced genomes. Of these enzymes, approximately 200 have been characterized functionally, and the three-dimensional crystal structures of approximately 40 have been reported. Since some SCOR enzymes are involved in hypertension, diabetes, breast cancer, and polycystic kidney disease, it is important to characterize the other members of the family for which the biological functions are currently unknown. Although the SCOR family appears to have only a single fully conserved residue, it was possible, using bioinformatics methods, to determine characteristic fingerprints composed of 30-40 residues that are conserved at the 70% or greater level in SCOR subgroups. These fingerprints permit reliable prediction of several important structure-function features including NAD/NADP cofactor preference. For example, the correlation of aspartate or arginine residues with NAD or NADP binding, respectively, predicts the cofactor preference of more than 70% of the SCOR proteins with unknown function. The analysis of conserved residues surrounding the cofactor has revealed the presence of previously undetected CH em leader O hydrogen bonds in the majority of the SCOR crystal structures, predicts the presence of similar hydrogen bonds in 90% of the SCOR proteins of unknown function, and suggests that these hydrogen bonds may play a critical role in the catalytic functions of these enzymes.

  11. Rational proteomics II: electrostatic nature of cofactor preference in the short-chain oxidoreductase (SCOR) enzyme family.

    Science.gov (United States)

    Pletnev, Vladimir Z; Weeks, Charles M; Duax, William L

    2004-11-01

    The dominant role of long-range electrostatic interatomic interactions in nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD/NADP) cofactor recognition has been shown for enzymes of the short-chain oxidoreductase (SCOR) family. An estimation of cofactor preference based only on the contribution of the electrostatic energy term to the total energy of enzyme-cofactor interaction has been tested for approximately 40 known three-dimensional (3D) crystal complexes and approximately 330 SCOR enzymes, with cofactor preference predicted by the presence of Asp or Arg recognition residues at specific 3D positions in the beta2alpha3 loop (Duax et al., Proteins 2003;53:931-943). The results obtained were found to be consistent with approximately 90% reliable cofactor assignments for those subsets. The procedure was then applied to approximately 170 SCOR enzymes with completely uncertain NAD/NADP dependence, due to the lack of Asp and Arg marker residues. The proposed 3D electrostatic approach for cofactor assignment ("3D_DeltaE(el)") has been implemented in an automatic screening procedure, and together with the use of marker residues proposed earlier (Duax et al., Proteins 2003;53:931-943), increases the level of reliable predictions for the putative SCORs from approximately 70% to approximately 90%. It is expected to be applicable for any NAD/NADP-dependent enzyme subset having at least 25-30% sequence identity, with at least one enzyme of known 3D crystal structure.

  12. Hybrid neural network model for simulating sorbitol synthesis by glucose-fructose oxidoreductase in Zymomonas mobilis CP4

    Directory of Open Access Journals (Sweden)

    Bravo S.

    2004-01-01

    Full Text Available A hybrid neural network model for simulating the process of enzymatic reduction of fructose to sorbitol process catalyzed by glucose-fructose oxidoreductase in Zymomonas mobilis CP4 is presented. Data used to derive and validate the model was obtained from experiments carried out under different conditions of pH, temperature and concentrations of both substrates (glucose and fructose involved in the reaction. Sonicated and lyophilized cells were used as source of the enzyme. The optimal pH for sorbitol synthesis at 30º C is 6.5. For a value of pH of 6, the optimal temperature is 35º C. The neural network in the model computes the value of the kinetic relationship. The hybrid neural network model is able to simulate changes in the substrates and product concentrations during sorbitol synthesis under pH and temperature conditions ranging between 5 and 7.5 and 25 and 40º C, respectively. Under these conditions the rate of sorbitol synthesis shows important differences. Values computed using the hybrid neural network model have an average error of 1.7·10-3 mole.

  13. Crystallization of the NADH-oxidizing domain of the Na+-translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae

    International Nuclear Information System (INIS)

    The FAD domain of the NqrF subunit from the Na+-translocating NADH dehydrogenase from V. cholerae has been purified and crystallized. A complete data set was recorded at 3.1 Å. The Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) from pathogenic and marine bacteria is a respiratory complex that couples the exergonic oxidation of NADH by quinone to the transport of Na+ across the membrane. The NqrF subunit oxidizes NADH and transfers the electrons to other redox cofactors in the enzyme. The FAD-containing domain of NqrF has been expressed, purified and crystallized. The purified NqrF FAD domain exhibited high rates of NADH oxidation and contained stoichiometric amounts of the FAD cofactor. Initial crystallization of the flavin domain was achieved by the sitting-drop technique using a Cartesian MicroSys4000 robot. Optimization of the crystallization conditions yielded yellow hexagonal crystals with dimensions of 30 × 30 × 70 µm. The protein mainly crystallizes in long hexagonal needles with a diameter of up to 30 µm. Crystals diffract to 2.8 Å and belong to space group P622, with unit-cell parameters a = b = 145.3, c = 90.2 Å, α = β = 90, γ = 120°

  14. Overproduction of stromal ferredoxin:NADPH oxidoreductase in H2O 2-accumulating Brassica napus leaf protoplasts.

    Science.gov (United States)

    Tewari, Rajesh Kumar; Satoh, Mamoru; Kado, Sayaka; Mishina, Kohei; Anma, Misato; Enami, Kazuhiko; Hanaoka, Mitsumasa; Watanabe, Masami

    2014-12-01

    The isolation of Brassica napus leaf protoplasts induces reactive oxygen species generation and accumulation in the chloroplasts. An activated isoform of NADPH oxidase-like protein was detected in the protoplasts and the protoplast chloroplasts. The purpose of this study is to define the NADH oxidase-like activities in the H2O2-accumulating protoplast chloroplasts. Proteomic analysis of this protein revealed an isoform of ferredoxin:NADPH oxidoreductase (FNR1). While leaves highly expressed the LFNR1 transcript, protoplasts decreased the expression significantly. The protoplast chloroplasts predominantly expressed soluble FNR1 proteins. While the albino leaves of white kale (Brassica oleracea var. acephala f. tricolor cv. white pigeon) expressed FNR1 protein at the same level as B. napus leaves, the protoplasts of albino leaves displayed reduced FNR1 expression. The albino leaf protoplasts of white kale generated and accumulated H2O2 in the cytoplasm and on the plasma membrane. Intracellular pH showed that the chloroplasts were acidic, which suggest that excess H(+) was generated in chloroplast stroma. NADPH content of the protoplast chloroplasts increased by over sixfold during the isolation of protoplasts. This study reports a possibility of mediating electrons to oxygen by an overproduced soluble FNR, and suggests that the FNR has a function in utilizing any excess reducing power of NADPH.

  15. Central role of the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) in sodium bioenergetics of Vibrio cholerae.

    Science.gov (United States)

    Steuber, Julia; Halang, Petra; Vorburger, Thomas; Steffen, Wojtek; Vohl, Georg; Fritz, Günter

    2014-12-01

    Vibrio cholerae is a Gram-negative bacterium that lives in brackish or sea water environments. Strains of V. cholerae carrying the pathogenicity islands infect the human gut and cause the fatal disease cholera. Vibrio cholerae maintains a Na(+) gradient at its cytoplasmic membrane that drives substrate uptake, motility, and efflux of antibiotics. Here, we summarize the major Na(+)-dependent transport processes and describe the central role of the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR), a primary Na(+) pump, in maintaining a Na(+)-motive force. The Na(+)-NQR is a membrane protein complex with a mass of about 220 kDa that couples the exergonic oxidation of NADH to the transport of Na(+) across the cytoplasmic membrane. We describe the molecular architecture of this respiratory complex and summarize the findings how electron transport might be coupled to Na(+)-translocation. Moreover, recent advances in the determination of the three-dimensional structure of this complex are reported.

  16. Crystallization of the NADH-oxidizing domain of the Na{sup +}-translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Minli [Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland); Türk, Karin [School of Engineering and Science, International University Bremen, 28759 Bremen (Germany); Diez, Joachim [Swiss Light Source at Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Grütter, Markus G. [Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland); Fritz, Günter, E-mail: guenter.fritz@uni-konstanz.de [Fachbereich Biologie, Universität Konstanz, Postfach M665, Universitätsstrasse 10, 78457 Konstanz (Germany); Steuber, Julia, E-mail: guenter.fritz@uni-konstanz.de [Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland)

    2006-02-01

    The FAD domain of the NqrF subunit from the Na{sup +}-translocating NADH dehydrogenase from V. cholerae has been purified and crystallized. A complete data set was recorded at 3.1 Å. The Na{sup +}-translocating NADH:quinone oxidoreductase (Na{sup +}-NQR) from pathogenic and marine bacteria is a respiratory complex that couples the exergonic oxidation of NADH by quinone to the transport of Na{sup +} across the membrane. The NqrF subunit oxidizes NADH and transfers the electrons to other redox cofactors in the enzyme. The FAD-containing domain of NqrF has been expressed, purified and crystallized. The purified NqrF FAD domain exhibited high rates of NADH oxidation and contained stoichiometric amounts of the FAD cofactor. Initial crystallization of the flavin domain was achieved by the sitting-drop technique using a Cartesian MicroSys4000 robot. Optimization of the crystallization conditions yielded yellow hexagonal crystals with dimensions of 30 × 30 × 70 µm. The protein mainly crystallizes in long hexagonal needles with a diameter of up to 30 µm. Crystals diffract to 2.8 Å and belong to space group P622, with unit-cell parameters a = b = 145.3, c = 90.2 Å, α = β = 90, γ = 120°.

  17. Crystallization of the NADH-oxidizing domain of the Na+-translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae

    Science.gov (United States)

    Tao, Minli; Türk, Karin; Diez, Joachim; Grütter, Markus G.; Fritz, Günter; Steuber, Julia

    2006-01-01

    The Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) from pathogenic and marine bacteria is a respiratory complex that couples the exergonic oxidation of NADH by quinone to the transport of Na+ across the membrane. The NqrF subunit oxidizes NADH and transfers the electrons to other redox cofactors in the enzyme. The FAD-containing domain of NqrF has been expressed, purified and crystallized. The purified NqrF FAD domain exhibited high rates of NADH oxidation and contained stoichiometric amounts of the FAD cofactor. Initial crystallization of the flavin domain was achieved by the sitting-drop technique using a Cartesian MicroSys4000 robot. Optimization of the crystallization conditions yielded yellow hexagonal crystals with dimensions of 30 × 30 × 70 µm. The protein mainly crystallizes in long hexagonal needles with a diameter of up to 30 µm. Crystals diffract to 2.8 Å and belong to space group P622, with unit-cell parameters a = b = 145.3, c = 90.2 Å, α = β = 90, γ = 120°. PMID:16511277

  18. Continuous production of gluconic acid and sorbitol from Jerusalem artichoke and glucose using an oxidoreductase of Zymomonas mobilis and inulinase.

    Science.gov (United States)

    Kim, D M; Kim, H S

    1992-02-01

    Gluconic acid and sorbitol were simultaneously produced from glucose and Jerusalem artichoke using a glucose-fructose oxidoreductase of Zymomonas mobilis and inulinase. Inulinase was immobilized on chitin by cross-linking with glutaraldehyde. Cells of Z. mobilis permeabilized with toluene were coimmobilized with chitin-immobilized inulinase in alginate beads. The optimum amounts of both chitin-immobilized inulinase and permeabilized cells for coimmobilization were determined, and operational conditions were optimized. In a continuous stirred tank reactor operation, the maximum productivities for gluconic acid and sorbitol were about 19.2 and 21.3 g/L/h, respectively, at the dilution rate of 0.23 h(-1) and the substrate concentration of 20%, but operational stability was low because of the abrasion of the beads. As an approach to increase the operational stability, a recycle packed-bed reactor (RPBR) was employed. In RPBR operation, the maximum productivities for gluconic acid and sorbitol were found to be 23.4 and 26.0 g/L/h, respectively, at the dilution rate of 0.35 h(-1) and the substrate concentration of 20% when the recirculation rate was fixed at 900 mL/h. Coimmobilized enzymes were stable for 250 h in a recycle packed-bed reactor without any loss of activity, while half-life in a continuous stirred tank reactor (CSTR) was observed to be about 150 h.

  19. Upregulation of NAD(PH:Quinone Oxidoreductase By Radiation Potentiates the Effect of Bioreductive β-Lapachone on Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eun K. Choi

    2007-08-01

    Full Text Available We found that (β-Lapachone ((β-Lap, a novel bioreductive drug, caused rapid apoptosis, clonogenic cell death in A549 human lung epithelial cancer cells in vitro in a dose-dependent manner. The clonogenic cell death caused by (β-Lap could be significantly inhibited by dicoumarol, an inhibitor of NAD(PH:quinone oxidoreductase (NO01, also by siRNA for NO01, demonstrating that N001-induced bioreduction of (β-Lap is an essential step in (β-Lap-induced cell death. Irradiation of A549 cells with 4 Gy caused a long-lasting upregulation of N001, thereby increasing N001mediated (β-Lap-induced cell deaths. Although the direct cause of (β-Lap-induced apoptosis is not yet clear, (β-Lap treatment reduced the expression of p53, NF-κB, whereas it increased cytochrome C release, caspase-3 activity, δ2AX foci formation. Importantly, (β-Lap treatment immediately after irradiation enhanced radiation-induced cell death, indicating that (β-Lap sensitizes cancer cells to radiation, in addition to directly killing some of the cells. The growth of A549 tumors induced in immunocompromised mice could be markedly suppressed by local radiation therapy when followed by (β-Lap treatment. This is the first study to demonstrate that combined radiotherapy, (β-Lap treatment can have a significant effect on human tumor xenografts.

  20. ArxA, a new clade of arsenite oxidase within the DMSO reductase family of molybdenum oxidoreductases

    Science.gov (United States)

    Zargar, Kamrun; Conrad, Alison; Bernick, David L.; Lowe, Todd M.; Stolc, Viktor; Hoeft, Shelley; Oremland, Ronald S.; Stolz, John; Saltikov, Chad W.

    2012-01-01

    Arsenotrophy, growth coupled to autotrophic arsenite oxidation or arsenate respiratory reduction, occurs only in the prokaryotic domain of life. The enzymes responsible for arsenotrophy belong to distinct clades within the DMSO reductase family of molybdenum-containing oxidoreductases: specifically arsenate respiratory reductase, ArrA, and arsenite oxidase, AioA (formerly referred to as AroA and AoxB). A new arsenite oxidase clade, ArxA, represented by the haloalkaliphilic bacterium Alkalilimnicola ehrlichii strain MLHE-1 was also identified in the photosynthetic purple sulfur bacterium Ectothiorhodospira sp. strain PHS-1. A draft genome sequence of PHS-1 was completed and an arx operon similar to MLHE-1 was identified. Gene expression studies showed that arxA was strongly induced with arsenite. Microbial ecology investigation led to the identification of additional arxA-like sequences in Mono Lake and Hot Creek sediments, both arsenic-rich environments in California. Phylogenetic analyses placed these sequences as distinct members of the ArxA clade of arsenite oxidases. ArxA-like sequences were also identified in metagenome sequences of several alkaline microbial mat environments of Yellowstone National Park hot springs. These results suggest that ArxA-type arsenite oxidases appear to be widely distributed in the environment presenting an opportunity for further investigations of the contribution of Arx-dependent arsenotrophy to the arsenic biogeochemical cycle.

  1. Glucose-fructose oxidoreductase, a new enzyme isolated from Zymomonas mobilis that is responsible for sorbitol production.

    Science.gov (United States)

    Zachariou, M; Scopes, R K

    1986-09-01

    The enzymes responsible for sorbitol formation in Zymomonas mobilis were investigated. A previously undescribed enzyme catalyzes the intermolecular oxidation-reduction of glucose and fructose to form gluconolactone and sorbitol. This enzyme has been purified; it had a subunit size of 40,000 daltons and is probably tetrameric at low pH. It contained tightly bound NADP as the hydrogen carrier and did not require any added cofactor for activity. In addition, a gluconolactonase has been isolated, although not completely purified. Together these two enzymes were capable of completely converting a 54% (wt/vol) equimolar mixture of glucose and fructose to sorbitol and sodium gluconate at the optimum pH of close to 6.2. The oxidoreductase had low affinities for its substrates, but natural environmental conditions would expose it to high concentrations of sugars. The amount of the enzyme in Z. mobilis cells was sufficient to account for the rate of sorbitol formation in vivo. However, the enzyme was present in the highest amounts when the cells were grown on glucose alone, and it was repressed by the presence of fructose; this was not the case with the gluconolactonase.

  2. Problematic detoxification of estrogen quinones by NAD(P)H-dependent quinone oxidoreductase and glutathione-S-transferase.

    Science.gov (United States)

    Chandrasena, R Esala P; Edirisinghe, Praneeth D; Bolton, Judy L; Thatcher, Gregory R J

    2008-07-01

    Estrogen exposure through early menarche, late menopause, and hormone replacement therapy increases the risk factor for hormone-dependent cancers. Although the molecular mechanisms are not completely established, DNA damage by quinone electrophilic reactive intermediates, derived from estrogen oxidative metabolism, is strongly implicated. A current hypothesis has 4-hydroxyestrone-o-quinone (4-OQE) acting as the proximal estrogen carcinogen, forming depurinating DNA adducts via Michael addition. One aspect of this hypothesis posits a key role for NAD(P)H-dependent quinone oxidoreductase (NQO1) in the reduction of 4-OQE and protection against estrogen carcinogenesis, despite two reports that 4-OQE is not a substrate for NQO1. 4-OQE is rapidly and efficiently trapped by GSH, allowing measurement of NADPH-dependent reduction of 4-OQE in the presence and absence of NQO1. 4-OQE was observed to be a substrate for NQO1, but the acceleration of NADPH-dependent reduction by NQO1 over the nonenzymic reaction is less than 10-fold and at more relevant nanomolar concentrations of substrate is less than 2-fold. An alternative detoxifying enzyme, glutathione-S-transferase, was observed to be a target for 4-OQE, rapidly undergoing covalent modification. These results indicate that a key role for NQO1 and GST in direct detoxification of 4-hydroxy-estrogen quinones is problematic. PMID:18588320

  3. Involvement of sulfide:quinone oxidoreductase in sulfur oxidation of an acidophilic iron-oxidizing bacterium, Acidithiobacillus ferrooxidans NASF-1.

    Science.gov (United States)

    Wakai, Satoshi; Kikumoto, Mei; Kanao, Tadayoshi; Kamimura, Kazuo

    2004-12-01

    The effects of cyanide, azide, and 2-n-Heptyl-4-hydroxy-quinoline-N-oxide (HQNO) on the oxidation of ferrous ion or elemental sulfur with Acidithiobacillus ferrooxidans NASF-1 cells grown in iron- or sulfur-medium were examined. The iron oxidation of both iron- and sulfur-grown cells was strongly inhibited by cyanide and azide, but not by HQNO. Sulfur oxidation was relatively resistant to cyanide and azide, and inhibited by HQNO. Higher sulfide oxidation, ubiquinol dehydrogenase activity, and sulfide:quinone oxidoreductase (SQR) activity were observed in sulfur-grown cells more than in iron-grown cells. Sulfide oxidation in the presence of ubiquinone with the membrane fraction was inhibited by HQNO, but not by cyanide, azide, antimycin A, and myxothiazol. The transcription of three genes, encoding an aa(3)-type cytochrome c oxidase (coxB), a bd-type ubiquinol oxidase (cydA), and an sqr, were measured by real-time reverse transcription polymerase chain reaction. The transcriptional levels of coxB and cydA genes were similar in sulfur- and iron-grown cells, but that of sqr was 3-fold higher in sulfur-grown cells than in iron-grown cells. A model is proposed for the oxidation of reduced inorganic sulfur compounds in A. ferrooxidans NASF-1 cells. PMID:15618623

  4. Insight Into the Radical Mechanism of Phycocyanobilin-Ferredoxin Oxidoreductase (Pcya) Revealed By X-Ray Crystallography And Biochemical Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Tu, S.-L.; Rockwell, N.; Lagarias, J.C.; Fisher, A.J.; /Inst. Plant Microb. Biol., Taipei /UC, Davis

    2007-07-13

    The X-ray crystal structure of the substrate-free form of phycocyanobilin (PCB)-ferredoxin oxidoreductase (PcyA; EC 1.3.7.5) from the cyanobacterium Nostoc sp. PCC7120 has been solved at 2.5 angstrom resolution. A comparative analysis of this structure with those recently reported for substrate-bound and substrate-free forms of PcyA from the cyanobacterium Synechocystis sp. PCC6803 (Hagiwara et al. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 27-32; Hagiwara et al. (2006) FEBS Lett. 580, 3823-3828) provides a compelling picture of substrate-induced changes in the PcyA enzyme and the chemical basis of PcyA's catalytic activity. On the basis of these structures and the biochemical analysis of site-directed mutants of Nostoc PcyA, including mutants reported in recent studies (Tu et al. (2006) J. Biol. Chem. 281, 3127-3136) as well as mutants described in this study, a revised mechanism for the PcyA-mediated four-electron reduction of biliverdin IX{alpha} to 3E/3Z-phycocyanobilin via enzyme-bound bilin radical intermediates is proposed. The mechanistic insight of these studies, along with homology modeling, have provided new insight into the catalytic mechanisms of other members of the ferredoxin-dependent bilin reductase family that are widespread in oxygenic photosynthetic organisms.

  5. Mitochondrial NADH:ubiquinone oxidoreductase (complex I) in eukaryotes: a highly conserved subunit composition highlighted by mining of protein databases.

    Science.gov (United States)

    Cardol, Pierre

    2011-11-01

    Complex I (NADH:ubiquinone oxidoreductase) is the largest enzyme of the mitochondrial respiratory chain. Compared to its bacterial counterpart which encompasses 14-17 subunits, mitochondrial complex I has almost tripled its subunit composition during evolution of eukaryotes, by recruitment of so-called accessory subunits, part of them being specific to distinct evolutionary lineages. The increasing availability of numerous broadly sampled eukaryotic genomes now enables the reconstruction of the evolutionary history of this large protein complex. Here, a combination of profile-based sequence comparisons and basic structural properties analyses at the protein level enabled to pinpoint homology relationships between complex I subunits from fungi, mammals or green plants, previously identified as "lineage-specific" subunits. In addition, homologs of at least 40 mammalian complex I subunits are present in representatives of all major eukaryote assemblages, half of them having not been investigated so far (Excavates, Chromalveolates, Amoebozoa). This analysis revealed that complex I was subject to a phenomenal increase in size that predated the diversification of extant eukaryotes, followed by very few lineage-specific additions/losses of subunits. The implications of this subunit conservation for studies of complex I are discussed. PMID:21749854

  6. Preliminary crystallographic data of the three homologues of the thiol–disulfide oxidoreductase DsbA in Neisseria meningitidis

    International Nuclear Information System (INIS)

    The Neisseria meningitidis genome possesses three genes encoding active DsbAs. To throw light on the reason for this genetic multiplicity, the three enzymes have been purified and crystallized. Bacterial virulence depends on the correct folding of surface-exposed proteins, a process that is catalyzed by the thiol-disulfide oxidoreductase DsbA, which facilitates the synthesis of disulfide bonds in Gram-negative bacteria. Uniquely among bacteria, the Neisseria meningitidis genome possesses three genes encoding active DsbAs: DsbA1, DsbA2 and DsbA3. DsbA1 and DsbA2 have been characterized as lipoproteins involved in natural competence and in host-interactive biology, while the function of DsbA3 remains unknown. In an attempt to shed light on the reason for this multiplicity of dsbA genes, the three enzymes from N. meningitidis have been purified and crystallized in the presence of high concentrations of ammonium sulfate. The best crystals were obtained using DsbA1 and DsbA3; they belong to the orthorhombic and tetragonal systems and diffract to 1.5 and 2.7 Å resolution, respectively

  7. Disulfide bond-dependent mechanism of protection against oxidative stress in pyruvate-ferredoxin oxidoreductase of anaerobic Desulfovibrio bacteria.

    Science.gov (United States)

    Vita, Nicolas; Hatchikian, E Claude; Nouailler, Matthieu; Dolla, Alain; Pieulle, Laetitia

    2008-01-22

    Oxidative decarboxylation of pyruvate forming acetyl-coenzyme A is a crucial step in many metabolic pathways. In most anaerobes, this reaction is carried out by pyruvate-ferredoxin oxidoreductase (PFOR), an enzyme normally oxygen sensitive except in Desulfovibrio africanus (Da), where it shows an abnormally high oxygen stability. Using site-directed mutagenesis, we have specified a disulfide bond-dependent protective mechanism against oxidative conditions in Da PFOR. Our data demonstrated that the two cysteine residues forming the only disulfide bond in the as-isolated PFOR are crucial for the stability of the enzyme in oxidative conditions. A methionine residue located in the environment of the proximal [4Fe-4S] cluster was also found to be essential for this protective mechanism. In vivo analysis demonstrated unambiguously that PFOR in Da cells as well as two other Desulfovibrio species was efficiently protected against oxidative stress. Importantly, a less active but stable Da PFOR in oxidized cells rapidly reactivated when returned to anaerobic medium. Our work demonstrates the existence of an elegant disulfide bond-dependent reversible mechanism, found in the Desulfovibrio species to protect one of the key enzymes implicated in the central metabolism of these strict anaerobes. This new mechanism could be considered as an adaptation strategy used by sulfate-reducing bacteria to cope with temporary oxidative conditions and to maintain an active dormancy. PMID:18161989

  8. Escherichia coli pyruvate:flavodoxin oxidoreductase, YdbK - regulation of expression and biological roles in protection against oxidative stress.

    Science.gov (United States)

    Nakayama, Takayuki; Yonekura, Shin-Ichiro; Yonei, Shuji; Zhang-Akiyama, Qiu-Mei

    2013-01-01

    E. coli YdbK is predicted to be a pyruvate:flavodoxin oxidoreductase (PFOR). However, enzymatic activity and the regulation of gene expression of it are not well understood. In this study, we found that E. coli cells overexpressing the ydbK gene had enhanced PFOR activity, indicating the product of ydbK to be a PFOR. The PFOR was labile to oxygen. The expression of ydbK was induced by superoxide generators such as methyl viologen (MV) in a SoxS-dependent manner after a lag period. We identified a critical element upstream of ydbK gene required for the induction by MV and proved direct binding of SoxS to the element. E. coli ydbK mutant was highly sensitive to MV, which was enhanced by additional inactivation of fpr gene encoding ferredoxin (flavodoxin):NADP(H) reductase (FPR). Aconitase activity, a superoxide sensor, was more extensively decreased by MV in the E. coli ydbK mutant than in wild-type strain. The induction level of soxS gene was higher in E. coli ydbK fpr double mutant than in wild-type strain. These results indicate that YdbK helps to protect cells from oxidative stress. It is possible that YdbK maintains the cellular redox state together with FPR and is involved in the reduction of oxidized proteins including SoxR in the late stages of the oxidative stress response in E. coli. PMID:24025246

  9. Synthesis and Antimicrobial Evaluation of Amixicile-Based Inhibitors of the Pyruvate-Ferredoxin Oxidoreductases of Anaerobic Bacteria and Epsilonproteobacteria.

    Science.gov (United States)

    Kennedy, Andrew J; Bruce, Alexandra M; Gineste, Catherine; Ballard, T Eric; Olekhnovich, Igor N; Macdonald, Timothy L; Hoffman, Paul S

    2016-07-01

    Amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the Epsilonproteobacteria (Campylobacter and Helicobacter). Amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (PFOR) and related enzymes by inhibiting the function of the vitamin B1 cofactor (thiamine pyrophosphate) by a novel mechanism. Here, we interrogate the amixicile scaffold, guided by docking simulations, direct PFOR inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4'-aminopyrimidine of thiamine pyrophosphate (TPP). The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biological activity against C. difficile Docking simulation results correlate well with mechanistic enzymology and nuclear magnetic resonance (NMR) studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B1 function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance. PMID:27090174

  10. Flexibility of thiamine diphosphate revealed by kinetic crystallographic studies of the reaction of pyruvate-ferredoxin oxidoreductase with pyruvate.

    Science.gov (United States)

    Cavazza, Christine; Contreras-Martel, Carlos; Pieulle, Laetitia; Chabrière, Eric; Hatchikian, E Claude; Fontecilla-Camps, Juan C

    2006-02-01

    Pyruvate-ferredoxin oxidoreductases (PFOR) are unique among thiamine pyrophosphate (ThDP)-containing enzymes in giving rise to a rather stable cofactor-based free-radical species upon the decarboxylation of their first substrate, pyruvate. We have obtained snapshots of unreacted and partially reacted (probably as a tetrahedral intermediate) pyruvate-PFOR complexes at different time intervals. We conclude that pyruvate decarboxylation involves very limited substrate-to-product movements but a significant displacement of the thiazolium moiety of ThDP. In this respect, PFOR seems to differ substantially from other ThDP-containing enzymes, such as transketolase and pyruvate decarboxylase. In addition, exposure of PFOR to oxygen in the presence of pyruvate results in significant inhibition of catalytic activity, both in solution and in the crystals. Examination of the crystal structure of inhibited PFOR suggests that the loss of activity results from oxime formation at the 4' amino substituent of the pyrimidine moiety of ThDP. PMID:16472741

  11. EPR spectroscopic and computational characterization of the hydroxyethylidene-thiamine pyrophosphate radical intermediate of pyruvate:ferredoxin oxidoreductase.

    Science.gov (United States)

    Mansoorabadi, Steven O; Seravalli, Javier; Furdui, Cristina; Krymov, Vladimir; Gerfen, Gary J; Begley, Tadhg P; Melnick, Jonathan; Ragsdale, Stephen W; Reed, George H

    2006-06-13

    The radical intermediate of pyruvate:ferredoxin oxidoreductase (PFOR) from Moorella thermoacetica was characterized using electron paramagnetic resonance (EPR) spectroscopy at X-band and D-band microwave frequencies. EPR spectra, obtained with various combinations of isotopically labeled substrate (pyruvate) and coenzyme (thiamine pyrophosphate (TPP)), were analyzed by spectral simulations. Parameters obtained from the simulations were compared with those predicted from electronic structure calculations on various radical structures. The g-values and 14N/15N-hyperfine splittings obtained from the spectra are consistent with a planar, hydroxyethylidene-thiamine pyrophosphate (HE-TPP) pi-radical, in which spin is delocalized onto the thiazolium sulfur and nitrogen atoms. The 1H-hyperfine splittings from the methyl group of pyruvate and the 13C-hyperfine splittings from C2 of both pyruvate and TPP are consistent with a model in which the pyruvate-derived oxygen atom of the HE-TPP radical forms a hydrogen bond. The hyperfine splitting constants and g-values are not compatible with those predicted for a nonplanar, sigma/n-type cation radical. PMID:16752902

  12. The role of pyruvate ferredoxin oxidoreductase in pyruvate synthesis during autotrophic growth by the Wood-Ljungdahl pathway.

    Science.gov (United States)

    Furdui, C; Ragsdale, S W

    2000-09-15

    Pyruvate:ferredoxin oxidoreductase (PFOR) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA and CO(2). The catalytic proficiency of this enzyme for the reverse reaction, pyruvate synthase, is poorly understood. Conversion of acetyl-CoA to pyruvate links the Wood-Ljungdahl pathway of autotrophic CO(2) fixation to the reductive tricarboxylic acid cycle, which in these autotrophic anaerobes is the stage for biosynthesis of all cellular macromolecules. The results described here demonstrate that the Clostridium thermoaceticum PFOR is a highly efficient pyruvate synthase. The Michaelis-Menten parameters for pyruvate synthesis by PFOR are: V(max) = 1.6 unit/mg (k(cat) = 3.2 s(-1)), K(m)(Acetyl-CoA) = 9 micrometer, and K(m)(CO(2)) = 2 mm. The intracellular concentrations of acetyl-CoA, CoASH, and pyruvate have been measured. The predicted rate of pyruvate synthesis at physiological concentrations of substrates clearly is sufficient to support the role of PFOR as a pyruvate synthase in vivo. Measurements of its k(cat)/K(m) values demonstrate that ferredoxin is a highly efficient electron carrier in both the oxidative and reductive reactions. On the other hand, rubredoxin is a poor substitute in the oxidative direction and is inept in donating electrons for pyruvate synthesis. PMID:10878009

  13. Alcohol and sex.

    Science.gov (United States)

    Vijayasenan, M E

    1981-01-14

    Diminished sexual functioning among individuals dependent upon alcohol has been assessed. Ninety-seven male patients entered the study, all inpatients as the unit for treatment of alcoholism and drug addiction (Villa 6) in Porirua Hospital, Porirua. The sexual ability of these patients before the development of alcoholism was also rated for the same items and this rating was used as a control. Of the 97 patients, 69 (71 percent) suffered from sexual dysfunction for a period more than 12 months prior to admission to hospital. The disturbances noted were diminished sexual desire (58 percent of patients), erectile impotence (16 percent), premature ejaculation (4 percent), ejaculatory in competence (22 percent). A high proportion of the alcoholics showed signs of sexual deviation-19 percent having performed sexual crimes and a further 28 percent having repeated thought of sexual crimes. The possible causes of alcohol induced sexual dysfunction are discussed.

  14. Alcohol consumption in adolescents

    Directory of Open Access Journals (Sweden)

    Ilona Plevová

    2016-03-01

    Full Text Available Aim: To determine the level of alcohol consumption in a selected group of adolescents. Design: A descriptive cross-sectional study. Methods: The data were obtained using a part of the standardized ESPAD questionnaire for assessing consumption of alcoholic beverages. The sample comprised 422 students from seven secondary schools of different types in the city of Ostrava. For statistical analysis, the chi-squared test and Fisher's exact test (for n ≤ 5 were used. The data were processed using Stata v. 10. Results: More than half of respondents first tried alcohol before the age of 15. The most frequent alcohol-related problems were unprotected sex, decreased school performance and problems with parents or friends. Incomplete families were found to be an important factor in adolescents preferring and more frequently drinking beer. Conclusion: The study confirmed results reported by the Europe-wide survey ESPAD, namely that adolescents start to drink alcohol as early as before they turn fifteen.

  15. Pentoxifylline for alcoholic hepatitis

    DEFF Research Database (Denmark)

    Whitfield, Kate; Rambaldi, Andrea; Wetterslev, Jørn;

    2009-01-01

    BACKGROUND: Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic hepatitis. Pentoxifylline is used to treat alcoholic hepatitis, but there has been no systematic review to assess its effects....... OBJECTIVES: To assess the benefits and harms of pentoxifylline in alcoholic hepatitis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS......, clinicaltrials.gov, and full text searches were conducted until August 2009. Manufacturers and authors were contacted. SELECTION CRITERIA: All randomised clinical trials of pentoxifylline in participants with alcoholic hepatitis compared to control were selected for inclusion. DATA COLLECTION AND ANALYSIS: Two...

  16. Phytotherapy of alcoholism.

    Science.gov (United States)

    Tomczyk, Michał; Zovko-Koncić, Marijana; Chrostek, Lech

    2012-02-01

    Alcoholism is a medical, social, and economic problem where treatment methods mostly include difficult and long-lasting psychotherapy and, in some cases, quite controversial pharmacological approaches. A number of medicinal plants and pure natural compounds are reported to have preventive and therapeutic effects on alcoholism and alcohol dependency, but their constituents, efficacy and mechanism of action are mostly unknown so far. Recently, kudzu [Pueraria lobata (Willd.) Ohwi], St. John's wort (Hypericum perforatum L.), danshen (Salvia miltiorrhiza Bge.), ginseng (Panax ginseng C.A. Mey.), Japanese raisin tree (Hovenia dulcis Thunb.), ibogaine (Tabernanthe iboga H. Bn.), evening primrose (Oenothera biennis L.), prickly pear fruit (Opuntia ficus indica (L.) Mill.), purple passionflower (Passiflora incarnata L.), thyme (Thymus vulgaris L.), fenugreek seed (Trigonella foenum-graecum L.), ginger (Zingiber officinale Roscoe) and many others drew the attention of researchers. Can, therefore, drugs of natural origin be helpful in the treatment of alcoholism or in decreasing alcohol consumption? PMID:22474979

  17. Alcohol Expectancies, Alcohol Use, and Hostility as Longitudinal Predictors of Alcohol-Related Aggression

    OpenAIRE

    Kachadourian, Lorig K.; Homish, Gregory G.; Quigley, Brian M; Leonard, Kenneth E.

    2011-01-01

    The direct and interactive effects of alcohol expectancies for aggression, dispositional hostility, and heavy alcohol consumption on alcohol-related physical aggression were examined across the first four years of marriage in a sample of 634 newlywed couples. For husbands, alcohol aggression expectancies predicted increases in alcohol-related aggression; across husbands and wives however, aggression expectancies were not found to interact with hostility or alcohol consumption to predict physi...

  18. 76 FR 26308 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-05-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Scientific Review Administrator, National Institutes On Alcohol Abuse & Alcoholism National, Institutes...

  19. 75 FR 10808 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-09

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, 5635...

  20. 75 FR 10291 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-05

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Initial Review..., MBA, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, Office...

  1. 76 FR 78014 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-15

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review...., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism, National Institutes...

  2. 76 FR 77841 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-14

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism,...

  3. 75 FR 38533 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-02

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Alcohol Abuse and Alcoholism, Office of Extramural Activities, Extramural Project Officer, 5635...

  4. 77 FR 22794 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-04-17

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Ph.D., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism...

  5. 75 FR 57473 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-09-21

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse and Alcoholism, Office of Extramural Activities,...

  6. 78 FR 42529 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-16

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review....D., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism,...

  7. 75 FR 63494 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-15

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis..., Extramural Project Review Branch, EPRB, National Institute on Alcohol Abuse and Alcoholism,...

  8. 75 FR 24961 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meetings

    Science.gov (United States)

    2010-05-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Extramural Activities, National Institutes of Health, National Institute on Alcohol Abuse & Alcoholism,...

  9. 78 FR 42530 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-16

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism,...

  10. Alcoholic Relatives and Their Impact on Alcohol-Related Beliefs.

    Science.gov (United States)

    Johnson, Patrick B.; And Others

    Although research on children of alcoholics indicates that they are at high risk for later problem drinking, the etiological dynamics associated with this heightened risk status are not yet understood. This study compared the alcohol-related beliefs of subjects who possessed close relatives with alcohol problems with alcohol-related beliefs of…

  11. [Genetic variations in alcohol dehydrogenase, drinking habits and alcoholism

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Rasmussen, S.; Tybjaerg-Hansen, A.;

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH), and genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. By genotyping 9,080 white men and women from the general population, we found that men and women with ADH1B slow versus fast alcohol...... degradation drank approximately 30% more alcohol per week and had a higher risk of everyday and heavy drinking, and of alcoholism. Individuals with ADH1C slow versus fast alcohol degradation had a higher risk of heavy drinking Udgivelsesdato: 2008/8/25...

  12. [Alcohol and working life].

    Science.gov (United States)

    Kaarne, Tiina; Aalto, Mauri

    2009-01-01

    Alcohol-related harm constitutes a significant factor decreasing work productivity. Of heavy alcohol users, most participate in working life. According to labour contract law, a person attending the workplace inebriated can be fired. If the employer applies a deferral to treatment practice, the drug- or alcohol-addicted person can be provided with the choice of therapy and rehabilitation instead of terminating the employment. According to the recent recommendation by the trade unions, organizations should have a program for preventing substance abuse. The employer should take care of the worker's intoxicant education and train the foremen to intervene in the situations on time. PMID:19492706

  13. Discovering Genes Involved in Alcohol Dependence and Other Alcohol Responses

    OpenAIRE

    Buck, Kari J.; Milner, Lauren C.; Denmark, Deaunne L.; Grant, Seth G.N.; Kozell, Laura B.

    2012-01-01

    The genetic determinants of alcoholism still are largely unknown, hindering effective treatment and prevention. Systematic approaches to gene discovery are critical if novel genes and mechanisms involved in alcohol dependence are to be identified. Although no animal model can duplicate all aspects of alcoholism in humans, robust animal models for specific alcohol-related traits, including physiological alcohol dependence and associated withdrawal, have been invaluable resources. Using a varie...

  14. Episodic Alcohol Consumption by Youths

    OpenAIRE

    Pereverzev, Vladimir Alexeevich

    2014-01-01

    AbstractThis paper presents evidence that even rare episodic alcohol consumption by young people is not harmless. Unsafe rare episodic alcohol consumption by youths (students) was reflected in the reduced attention concentration and lower academic buoyancy, compared to those who completely abstain from alcohol. Key Words: Alcohol, youth, students, attention concentration, academic buoyancy 

  15. Deletion of P399{sub E}401 in NADPH cytochrome P450 oxidoreductase results in partial mixed oxidase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Flueck, Christa E., E-mail: christa.flueck@dkf.unibe.ch [Pediatric Endocrinology, Diabetology and Metabolism, University Children' s Hospital, Bern (Switzerland); Mallet, Delphine [Service d' Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Hofer, Gaby [Pediatric Endocrinology, Diabetology and Metabolism, University Children' s Hospital, Bern (Switzerland); Samara-Boustani, Dinane [Hopital Necker-Enfants malades, Paris (France); Leger, Juliane [Hopital Robert Debre, Paris (France); Polak, Michel [Hopital Necker-Enfants malades, Paris (France); Morel, Yves [Service d' Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Pandey, Amit V., E-mail: amit@pandeylab.org [Pediatric Endocrinology, Diabetology and Metabolism, University Children' s Hospital, Bern (Switzerland)

    2011-09-09

    Highlights: {yields} Mutations in human POR cause congenital adrenal hyperplasia. {yields} We are reporting a novel 3 amino acid deletion mutation in POR P399{sub E}401del. {yields} POR mutation P399{sub E}401del decreased P450 activities by 60-85%. {yields} Impairment of steroid metabolism may be caused by multiple hits. {yields} Severity of aromatase inhibition is related to degree of in utero virilization. -- Abstract: P450 oxidoreductase (POR) is the electron donor for all microsomal P450s including steroidogenic enzymes CYP17A1, CYP19A1 and CYP21A2. We found a novel POR mutation P399{sub E}401del in two unrelated Turkish patients with 46,XX disorder of sexual development. Recombinant POR proteins were produced in yeast and tested for their ability to support steroid metabolizing P450 activities. In comparison to wild-type POR, the P399{sub E}401del protein was found to decrease catalytic efficiency of 21-hydroxylation of progesterone by 68%, 17{alpha}-hydroxylation of progesterone by 76%, 17,20-lyase action on 17OH-pregnenolone by 69%, aromatization of androstenedione by 85% and cytochrome c reduction activity by 80%. Protein structure analysis of the three amino acid deletion P399{sub E}401 revealed reduced stability and flexibility of the mutant. In conclusion, P399{sub E}401del is a novel mutation in POR that provides valuable genotype-phenotype and structure-function correlation for mutations in a different region of POR compared to previous studies. Characterization of P399{sub E}401del provides further insight into specificity of different P450s for interaction with POR as well as nature of metabolic disruptions caused by more pronounced effect on specific P450s like CYP17A1 and aromatase.

  16. Simultaneous involvement of a tungsten-containing aldehyde:ferredoxin oxidoreductase and a phenylacetaldehyde dehydrogenase in anaerobic phenylalanine metabolism.

    Science.gov (United States)

    Debnar-Daumler, Carlotta; Seubert, Andreas; Schmitt, Georg; Heider, Johann

    2014-01-01

    Anaerobic phenylalanine metabolism in the denitrifying betaproteobacterium Aromatoleum aromaticum is initiated by conversion of phenylalanine to phenylacetate, which is further metabolized via benzoyl-coenzyme A (CoA). The formation of phenylacetate is catalyzed by phenylalanine transaminase, phenylpyruvate decarboxylase, and a phenylacetaldehyde-oxidizing enzyme. The presence of these enzymes was detected in extracts of cells grown with phenylalanine and nitrate. We found that two distinct enzymes are involved in the oxidation of phenylacetaldehyde to phenylacetate, an aldehyde:ferredoxin oxidoreductase (AOR) and a phenylacetaldehyde dehydrogenase (PDH). Based on sequence comparison, growth studies with various tungstate concentrations, and metal analysis of the enriched enzyme, AOR was shown to be a tungsten-containing enzyme, necessitating specific cofactor biosynthetic pathways for molybdenum- and tungsten-dependent enzymes simultaneously. We predict from the genome sequence that most enzymes of molybdopterin biosynthesis are shared, while the molybdate/tungstate uptake systems are duplicated and specialized paralogs of the sulfur-inserting MoaD and the metal-inserting MoeA proteins seem to be involved in dedicating biosynthesis toward molybdenum or tungsten cofactors. We also characterized PDH biochemically and identified both NAD(+) and NADP(+) as electron acceptors. We identified the gene coding for the enzyme and purified a recombinant Strep-tagged PDH variant. The homotetrameric enzyme is highly specific for phenylacetaldehyde, has cooperative kinetics toward the substrate, and shows considerable substrate inhibition. Our data suggest that A. aromaticum utilizes PDH as the primary enzyme during anaerobic phenylalanine degradation, whereas AOR is not essential for the metabolic pathway. We hypothesize a function as a detoxifying enzyme if high aldehyde concentrations accumulate in the cytoplasm, which would lead to substrate inhibition of PDH.

  17. The short-chain oxidoreductase Q9HYA2 from Pseudomonas aeruginosa PAO1 contains an atypical catalytic center.

    Science.gov (United States)

    Huether, Robert; Mao, Qilong; Duax, William L; Umland, Timothy C

    2010-05-01

    The characteristic oxidation or reduction reaction mechanisms of short-chain oxidoreductase (SCOR) enzymes involve a highly conserved Asp-Ser-Tyr-Lys catalytic tetrad. The SCOR enzyme Q9HYA2 from the pathogenic bacterium Pseudomonas aeruginosa was recognized to possess an atypical catalytic tetrad composed of Lys118-Ser146-Thr159-Arg163. Orthologs of Q9HYA2 containing the unusual catalytic tetrad along with conserved substrate and cofactor recognition residues were identified in 27 additional species, the majority of which are bacterial pathogens. However, this atypical catalytic tetrad was not represented within the Protein Data Bank. The crystal structures of unligated and NADPH-complexed Q9HYA2 were determined at 2.3 A resolution. Structural alignment to a polyketide ketoreductase (KR), a typical SCOR, demonstrated that Q9HYA2's Lys118, Ser146, and Arg163 superimposed upon the KR's catalytic Asp114, Ser144, and Lys161, respectively. However, only the backbone of Q9HYA2's Thr159 overlapped KR's catalytic Tyr157. The Thr159 hydroxyl in apo Q9HYA2 is poorly positioned for participating in catalysis. In the Q9HYA2-NADPH complex, the Thr159 side chain was modeled in two alternate rotamers, one of which is positioned to interact with other members of the tetrad and the bound cofactor. A chloride ion is bound at the position normally occupied by the catalytic tyrosine hydroxyl. The putative active site of Q9HYA2 contains a chemical moiety at each catalytically important position of a typical SCOR enzyme. This is the first observation of a SCOR protein with this alternate catalytic center that includes threonine replacing the catalytic tyrosine and an ion replacing the hydroxyl moiety of the catalytic tyrosine.

  18. Cooperation of NAD(P)H:quinone oxidoreductase 1 and UDP-glucuronosyltransferases reduces menadione cytotoxicity in HEK293 cells.

    Science.gov (United States)

    Nishiyama, Takahito; Izawa, Tadashi; Usami, Mami; Ohnuma, Tomokazu; Ogura, Kenichiro; Hiratsuka, Akira

    2010-04-01

    Previous studies have shown that NAD(P)H:quinone oxidoreductase 1 (NQO1) plays an important role in the detoxification of menadione (2-methyl-1,4-naphthoquinone, also known as vitamin K3). However, menadiol (2-methyl-1,4-naphthalenediol) formed from menadione by NQO1-mediated reduction continues to be an unstable substance, which undergoes the reformation of menadione with concomitant formation of reactive oxygen species (ROS). Hence, we focused on the roles of phase II enzymes, with particular attention to UDP-glucuronosyltransferases (UGTs), in the detoxification process of menadione. In this study, we established an HEK293 cell line stably expressing NQO1 (HEK293/NQO1) and HEK293/NQO1 cell lines with doxycycline (DOX)-regulated expression of UGT1A6 (HEK293/NQO1/UGT1A6) and UGT1A10 (HEK293/NQO1/UGT1A10), and evaluated the role of NQO1 and UGTs against menadione-induced cytotoxicity. Our results differed from those of previous studies. HEK293/NQO1 was the most sensitive cell line to menadione cytotoxicity among cell lines established in this study. These phenomena were also observed in HEK293/NQO1/UGT1A6 and HEK293/NQO1/UGT1A10 cells in which the expression of UGT was suppressed by DOX treatment. On the contrary, HEK293/NQO1/UGT1A6 and HEK293/NQO1/UGT1A10 cells without DOX treatment were resistant to menadione-induced cytotoxicity. These results demonstrated that NQO1 is not a detoxification enzyme for menadione and that UGT-mediated glucuronidation of menadiol is the most important detoxification process.

  19. Legionella pneumophila utilizes a Single Player Disulfide-Bond Oxidoreductase System to Manage Disulfide Bond Formation and Isomerization

    Science.gov (United States)

    Kpadeh, Zegbeh Z.; Day, Shandra R.; Mills, Brandy W.; Hoffman, Paul S.

    2015-01-01

    Legionella pneumophila uses a single homodimeric disulfide bond (DSB) oxidoreductase DsbA2 to catalyze extracytoplasmic protein folding and to correct DSB errors through protein-disulfide isomerase (PDI) activity. In Escherichia coli, these functions are separated to avoid futile cycling. In L. pneumophila, DsbA2 is maintained as a mixture of disulfides (S-S) and free thiols (SH), but when expressed in E. coli, only the SH form is observed. We provide evidence to suggest that structural differences in DsbB oxidases (LpDsbB1 and LpDsbB2) and DsbD reductases (LpDsbD1 and LpDsbD2) (compared to E. coli) permit bifunctional activities without creating a futile cycle. LpdsbB1 and LpdsbB2 partially complemented an EcdsbB mutant while neither LpdsbD1 nor LpdsbD2 complemented an EcdsbD mutant unless DsbA2 was also expressed. When the dsb genes of E. coli were replaced with those of L. pneumophila, motility was restored and DsbA2 was present as a mixture of redox forms. A dominant-negative approach to interfere with DsbA2 function in L. pneumophila determined that DSB oxidase activity was necessary for intracellular multiplication and assembly/function of the Dot/Icm Type IVb secretion system. Our studies show that a single-player system may escape the futile cycle trap by limiting transfer of reducing equivalents from LpDsbDs to DsbA2. PMID:25534767

  20. Optimized inhibition assays reveal different inhibitory responses of hydroxylamine oxidoreductases from beta- and gamma-proteobacterial ammonium-oxidizing bacteria.

    Science.gov (United States)

    Nishigaya, Yuki; Fujimoto, Zui; Yamazaki, Toshimasa

    2016-07-29

    Ammonia-oxidizing bacteria (AOB), ubiquitous chemoautotrophic bacteria, convert ammonia (NH3) to nitrite (NO2(-)) via hydroxylamine as energy source. Excessive growth of AOB, enhanced by applying large amounts of ammonium-fertilizer to the farmland, leads to nitrogen leaching and nitrous oxide gas emission. To suppress these unfavorable phenomena, nitrification inhibitors, AOB specific bactericides, are widely used in fertilized farmland. However, new nitrification inhibitors are desired because of toxicity and weak-effects of currently used inhibitors. Toward development of novel nitrification inhibitors that target hydroxylamine oxidoreductase (HAO), a key enzyme of nitrification in AOB, we established inhibitor evaluation systems that include simplified HAO purification procedure and high-throughput HAO activity assays for the purified enzymes and for the live AOB cells. The new assay systems allowed us to observe distinct inhibitory responses of HAOs from beta-proteobacterial AOB (βAOB) Nitrosomonas europaea (NeHAO) and gamma-proteobacterial AOB (γAOB) Nitrosococcus oceani (NoHAO) against phenylhydrazine, a well-known suicide inhibitor for NeHAO. Consistently, the live cells of N. europaea, Nitrosomonas sp. JPCCT2 and Nitrosospira multiformis of βAOB displayed higher responses to phenylhydrazine than those of γAOB N. oceani. Our homology modeling studies suggest that different inhibitory responses of βAOB and γAOB are originated from different local environments around the substrate-binding sites of HAOs in these two classes of bacteria due to substitutions of two residues. The results reported herein strongly recommend inhibitor screenings against both NeHAO of βAOB and NoHAO of γAOB to develop HAO-targeting nitrification inhibitors with wide anti-AOB spectra. PMID:27173879

  1. 黄嘌呤氧化还原酶与代谢综合征%Xanthine oxidoreductase and metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    严天连; 徐承富; 厉有名

    2013-01-01

    黄嘌呤氧化还原酶(XOR)通过将嘌呤分解为尿酸,控制着人体内嘌呤代谢的限速步骤.近年来研究表明XOR活性的异常不仅可导致高尿酸血症和痛风,还积极地参与了代谢综合征的发生、发展.XOR如何影响肥胖、高血压、动脉粥样硬化、糖尿病等代谢综合征相关疾病尚不明确,其可能机制包括调节脂质代谢转录调控因子,影响尿酸、一氧化氮及活性氧簇的生成等.XOR抑制剂如别嘌呤醇和非布索坦对上述疾病有一定的保护效果,这为代谢综合征的防治提供了新思路.%Xanthine oxidoreductase (XOR) controls the rate limiting step of purine catabolism by converting xanthine to uric acid.Recent studies showed that the abnormal activity of XOR not only led to hyperuricemia and gout,but also actively participated in the development of metabolic syndrome.However,how XOR affects obesity,hypertension,atherosclerosis,diabetes and other metabolic syndrome related diseases remains unclear.Its possible mechanism includes regulating the transcription factors of adipogenesis,affecting the synthesis of uric acid,nitric oxide and reactive oxygen species,etc.XOR inhibitor such as allopurinol and febuxostat has a protective effect of the diseases mentioned above.These findings would provide new ideas for treatment of metabolic syndrome.

  2. Application of nanodisc technology for direct electrochemical investigation of plant cytochrome P450s and their NADPH P450 oxidoreductase.

    Science.gov (United States)

    Bavishi, Krutika; Laursen, Tomas; Martinez, Karen L; Møller, Birger Lindberg; Della Pia, Eduardo Antonio

    2016-01-01

    Direct electrochemistry of cytochrome P450 containing systems has primarily focused on investigating enzymes from microbes and animals for bio-sensing applications. Plant P450s receive electrons from NADPH P450 oxidoreductase (POR) to orchestrate the bio-synthesis of a plethora of commercially valuable compounds. In this report, full length CYP79A1, CYP71E1 and POR of the dhurrin pathway in Sorghum bicolor were reconstituted individually in nanoscale lipid patches, "nanodiscs", and directly immobilized on unmodified gold electrodes. Cyclic voltammograms of CYP79A1 and CYP71E1 revealed reversible redox peaks with average midpoint potentials of 80 ± 5 mV and 72 ± 5 mV vs. Ag/AgCl, respectively. POR yielded two pairs of redox peaks with midpoint potentials of 90 ± 5 mV and -300 ± 10 mV, respectively. The average heterogeneous electron transfer rate constant was calculated to be ~1.5 s(-1). POR was electro-catalytically active while the P450s generated hydrogen peroxide (H2O2). These nanodisc-based investigations lay the prospects and guidelines for construction of a simplified platform to perform mediator-free, direct electrochemistry of non-engineered cytochromes P450 under native-like conditions. It is also a prelude for driving plant P450 systems electronically for simplified and cost-effective screening of potential substrates/inhibitors and fabrication of nano-bioreactors for synthesis of high value natural products. PMID:27386958

  3. Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni.

    Science.gov (United States)

    Hoffman, Paul S; Sisson, Gary; Croxen, Matthew A; Welch, Kevin; Harman, W Dean; Cremades, Nunilo; Morash, Michael G

    2007-03-01

    Nitazoxanide (NTZ) exhibits broad-spectrum activity against anaerobic bacteria and parasites and the ulcer-causing pathogen Helicobacter pylori. Here we show that NTZ is a noncompetitive inhibitor (K(i), 2 to 10 microM) of the pyruvate:ferredoxin/flavodoxin oxidoreductases (PFORs) of Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis, Clostridium difficile, Clostridium perfringens, H. pylori, and Campylobacter jejuni and is weakly active against the pyruvate dehydrogenase of Escherichia coli. To further mechanistic studies, the PFOR operon of H. pylori was cloned and overexpressed in E. coli, and the multisubunit complex was purified by ion-exchange chromatography. Pyruvate-dependent PFOR activity with NTZ, as measured by a decrease in absorbance at 418 nm (spectral shift from 418 to 351 nm), unlike the reduction of viologen dyes, did not result in the accumulation of products (acetyl coenzyme A and CO(2)) and pyruvate was not consumed in the reaction. NTZ did not displace the thiamine pyrophosphate (TPP) cofactor of PFOR, and the 351-nm absorbing form of NTZ was inactive. Optical scans and (1)H nuclear magnetic resonance analyses determined that the spectral shift (A(418) to A(351)) of NTZ was due to protonation of the anion (NTZ(-)) of the 2-amino group of the thiazole ring which could be generated with the pure compound under acidic solutions (pK(a) = 6.18). We propose that NTZ(-) intercepts PFOR at an early step in the formation of the lactyl-TPP transition intermediate, resulting in the reversal of pyruvate binding prior to decarboxylation and in coordination with proton transfer to NTZ. Thus, NTZ might be the first example of an antimicrobial that targets the "activated cofactor" of an enzymatic reaction rather than its substrate or catalytic sites, a novel mechanism that may escape mutation-based drug resistance. PMID:17158936

  4. Amixicile, a novel inhibitor of pyruvate: ferredoxin oxidoreductase, shows efficacy against Clostridium difficile in a mouse infection model.

    Science.gov (United States)

    Warren, Cirle A; van Opstal, Edward; Ballard, T Eric; Kennedy, Andrew; Wang, Xia; Riggins, Mary; Olekhnovich, Igor; Warthan, Michelle; Kolling, Glynis L; Guerrant, Richard L; Macdonald, Timothy L; Hoffman, Paul S

    2012-08-01

    Clostridium difficile infection (CDI) is a serious diarrheal disease that often develops following prior antibiotic usage. One of the major problems with current therapies (oral vancomycin and metronidazole) is the high rate of recurrence. Nitazoxanide (NTZ), an inhibitor of pyruvate:ferredoxin oxidoreductase (PFOR) in anaerobic bacteria, parasites, Helicobacter pylori, and Campylobacter jejuni, also shows clinical efficacy against CDI. From a library of ∼250 analogues of NTZ, we identified leads with increased potency for PFOR. MIC screens indicated in vitro activity in the 0.05- to 2-μg/ml range against C. difficile. To improve solubility, we replaced the 2-acetoxy group with propylamine, producing amixicile, a soluble (10 mg/ml), nontoxic (cell-based assay) lead that produced no adverse effects in mice by oral or intraperitoneal (i.p.) routes at 200 mg/kg of body weight/day. In initial efficacy testing in mice treated (20 mg/kg/day, 5 days each) 1 day after receiving a lethal inoculum of C. difficile, amixicile showed slightly less protection than did vancomycin by day 5. However, in an optimized CDI model, amixicile showed equivalence to vancomycin and fidaxomicin at day 5 and there was significantly greater survival produced by amixicile than by the other drugs on day 12. All three drugs were comparable by measures of weight loss/gain and severity of disease. Recurrence of CDI was common for mice treated with vancomycin or fidaxomicin but not for mice receiving amixicile or NTZ. These results suggest that gut repopulation with beneficial (non-PFOR) bacteria, considered essential for protection against CDI, rebounds much sooner with amixicile therapy than with vancomycin or fidaxomicin. If the mouse model is indeed predictive of human CDI disease, then amixicile, a novel PFOR inhibitor, appears to be a very promising new candidate for treatment of CDI. PMID:22585229

  5. Interplay Between the Oxidoreductase PDIA6 and microRNA-322 Controls the Response to Disrupted Endoplasmic Reticulum Calcium Homeostasis

    Science.gov (United States)

    Groenendyk, Jody; Peng, Zhenling; Dudek, Elzbieta; Fan, Xiao; Mizianty, Marcin J.; Dufey, Estefanie; Urra, Hery; Sepulveda, Denisse; Rojas-Rivera, Diego; Lim, Yunki; Kim, Do Han; Baretta, Kayla; Srikanth, Sonal; Gwack, Yousang; Ahnn, Joohong; Kaufman, Randal J.; Lee, Sun-Kyung; Hetz, Claudio; Kurgan, Lukasz; Michalak, Marek

    2016-01-01

    The disruption of the energy or nutrient balance triggers endoplasmic reticulum (ER) stress, a process that mobilizes various strategies, collectively called the unfolded protein response (UPR), which reestablish homeostasis of the ER and cell. Activation of the UPR stress sensor IRE1α (inositol-requiring enzyme 1α) stimulates its endoribonuclease activity, leading to the generation of the mRNA encoding the transcription factor XBP1 (X-box binding protein 1), which regulates the transcription of genes encoding factors involved in controlling the quality and folding of proteins. We found that the activity of IRE1α was regulated by the ER oxidoreductase PDIA6 (protein disulfide isomerase A6) and the microRNA miR-322 in response to disruption of ER Ca2+ homeostasis. PDIA6 interacted with IRE1α and enhanced IRE1α activity as monitored by phosphorylation of IRE1α and XBP1 mRNA splicing, but PDIA6 did not substantially affect the activity of other pathways that mediate responses to ER stress. ER Ca2+ depletion and activation of store operated Ca2+ entry reduced the abundance of the microRNA miR-322, which increased PDIA6 mRNA stability and consequently IRE1α activity during the ER stress response. In vivo experiments with mice and worms showed that the induction of ER stress correlated with decreased miR-322 abundance, increased PDIA6 mRNA abundance, or both. Together these findings demonstrated that ER Ca2+, PDIA6, IRE1α, and miR-322 function in a dynamic feedback loop modulating the UPR under conditions of disrupted ER Ca2+ homeostasis. PMID:24917591

  6. ALCOHOL AND HEART RHYTHM DISORDERS

    Directory of Open Access Journals (Sweden)

    A. O. Yusupova

    2015-01-01

    Full Text Available Alcohol abuse and particularly extension of alcohol consumption in alcohol diseas increases the risk of cardiac arrhythmias development and aggravates existing arrhythmias. Patients do not always receive the necessary specific treatment due to lack of detection of the ethanol genesis of these arrhythmias. Management of patients with alcohol abuse and alcohol dependence, including its cardiac complications among other cardiac arrhythmias should use both antiarrhythmic and anti-alcohol drugs and antidepressants. Such issues as diagnosis and management of patients with alcohol-induced cardiac arrhythmias are presented.

  7. Alcohol Facts and Statistics

    Science.gov (United States)

    ... other persons of the same age. 26 Consequences—Researchers estimate that each year: 1,825 college students between the ages of 18 and 24 die from alcohol-related unintentional injuries, including motor-vehicle crashes. 27 ...

  8. Alcohol and Migraine

    Science.gov (United States)

    ... tension-type headache. Cluster headache patients have higher alcohol sensitivity (about 50-80%). In a forward-looking study (PAMINA) published in 2007 Austrian researchers examined a large number of factors related to ...

  9. Alcohol Facts and Statistics

    Science.gov (United States)

    ... deaths (31 percent of overall driving fatalities). 11 Economic Burden: In 2010, alcohol misuse problems cost the ... 18–24: Changes from 1998 to 2001. Annual Review of Public Health 26: 259–279, 2005. PMID: ...

  10. Fetal Alcohol Spectrum Disorders

    Science.gov (United States)

    ... can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Effects can include physical and behavioral problems such as trouble with Learning and remembering Understanding and following directions Controlling emotions Communicating and socializing Daily life skills, such as ...

  11. [Prevention of alcohol dependence].

    Science.gov (United States)

    Trova, A C; Paparrigopoulos, Th; Liappas, I; Ginieri-Coccossis, M

    2015-01-01

    With the exception of cardiovascular diseases, no other medical condition causes more serious dysfunction or premature deaths than alcohol-related problems. Research results indicate that alcohol dependent individuals present an exceptionally poor level of quality of life. This is an outcome that highlights the necessity of planning and implementing preventive interventions on biological, psychological or social level, to be provided to individuals who make alcohol abuse, as well as to their families. Preventive interventions can be considered on three levels of prevention: (a) primary prevention, which is focused on the protection of healthy individuals from alcohol abuse and dependence, and may be provided on a universal, selective or indicated level, (b) secondary prevention, which aims at the prevention of deterioration regarding alcoholic dependence and relapse, in the cases of individuals already diagnosed with the condition and (c) tertiary prevention, which is focused at minimizing deterioration of functioning in chronically sufferers from alcoholic dependence. The term "quaternary prevention" can be used for the prevention of relapse. As for primary prevention, interventions focus on assessing the risk of falling into problematic use, enhancing protective factors and providing information and health education in general. These interventions can be delivered in schools or in places of work and recreation for young people. In this context, various programs have been applied in different countries, including Greece with positive results (Preventure, Alcolocks, LST, SFP, Alcohol Ignition Interlock Device). Secondary prevention includes counseling and structured help with the delivery of programs in schools and in high risk groups for alcohol dependence (SAP, LST). These programs aim at the development of alcohol refusal skills and behaviors, the adoption of models of behaviors resisting alcohol use, as well as reinforcement of general social skills. In the

  12. Alcohol and Pregnancy

    Medline Plus

    Full Text Available ... and premature birth Zika virus and pregnancy Microcephaly Medicine safety and pregnancy Birth defects prevention Learn how ... a healthy weight and avoiding alcohol and street drugs . Featured articles March of Dimes Premature Birth Report ...

  13. Alcohol advertising and youth.

    Science.gov (United States)

    Martin, Susan E; Snyder, Leslie B; Hamilton, Mark; Fleming-Milici, Fran; Slater, Michael D; Stacy, Alan; Chen, Meng-Jinn; Grube, Joel W

    2002-06-01

    This article presents the proceedings of a symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. The symposium was organized and chaired by Joel W. Grube. The presentations and presenters were (1) Introduction and background, by Susan E. Martin; (2) The effect of alcohol ads on youth 15-26 years old, by Leslie Snyder, Mark Hamilton, Fran Fleming-Milici, and Michael D. Slater; (3) A comparison of exposure to alcohol advertising and drinking behavior in elementary versus middle school children, by Phyllis L. Ellickson and Rebecca L. Collins; (4) USC health and advertising project: assessment study on alcohol advertisement memory and exposure, by Alan Stacy; and (5) TV beer and soft drink advertising: what young people like and what effects? by Meng-Jinn Chen and Joel W. Grube. PMID:12068260

  14. Fetal alcohol syndrome

    Science.gov (United States)

    ... development. There also may be problems with the face and bones. Tests include: Blood alcohol level in pregnant women who show signs of being drunk (intoxicated) Brain imaging studies (CT or MRI) after the child is born Pregnancy ultrasound

  15. When alcohol acts

    DEFF Research Database (Denmark)

    Demant, Jakob

    2009-01-01

      Sociological studies into alcohol use seem to find it difficult to deal with the substance itself. Alcohol tends to be reduced to a symbol of a social process and in this way the sociological research loses sight of effects beyond the social. This paper suggests a new theoretical approach...... to the study of alcohol and teenagers' (romantic) relationships, inspired by actor-network theory (ANT). The central feature of ANT is to search for relationships, or rather networks, between all things relevant to the phenomenon. All material and semantic structures, things, persons, discourses, etc....... that influence a given situation are described as actants and are entered into the analysis. The aim of this paper is to propose a way of including materiality in sociological analyses of alcohol and to explore ways of using focus group interview material in ANT-inspired analysis. By analyzing a girl...

  16. Alcohol and Heart Health

    Science.gov (United States)

    ... Restaurant Deciphering the Menu Ordering Your Meal Eating Fast Food Dining Out Tips by Cuisine Physical Activity Fitness ... other things. For example, excessive amounts of alcoholic consumption could be harmful by increasing the risk of ...

  17. Advances in Alcoholism Treatment

    OpenAIRE

    Huebner, Robert B.; Kantor, Lori Wolfgang

    2011-01-01

    Researchers are working on numerous and varied approaches to improving the accessibility, quality, effectiveness, and cost-effectiveness of treatment for alcohol use disorders (AUDs). This overview article summarizes the approaches reviewed in this issue, including potential future developments for alcoholism treatment, such as medications development, behavioral therapy, advances in technology that are being used to improve treatment, integrated care of patients with AUDs and co-occurring di...

  18. Alcohol and Sexual Assault

    OpenAIRE

    Abbey, Antonia; Zawacki, Tina; Buck, Philip O; Clinton, A. Monique; McAuslan, Pam

    2001-01-01

    Conservative estimates of sexual assault prevalence suggest that 25 percent of American women have experienced sexual assault, including rape. Approximately one-half of those cases involve alcohol consumption by the perpetrator, victim, or both. Alcohol contributes to sexual assault through multiple pathways, often exacerbating existing risk factors. Beliefs about alcohol’s effects on sexual and aggressive behavior, stereotypes about drinking women, and alcohol’s effects on cognitive and moto...

  19. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  20. Alcohol: Pleasures and Problems.

    Science.gov (United States)

    Finn, Peter; Lawson, Jane

    This student booklet is to be used in conjunction with the Teacher Manual and films of the DIAL A-L-C-O-H-O-L series. It presents facts and illustrations on the use of alcohol, and is intended to aid young people in deciding whether or not to drink. This booklet is divided into the following parts: (1) Introduction; (2) The Enjoyment of Drinking;…

  1. Alcohol-attributable and alcohol-preventable mortality in Denmark

    DEFF Research Database (Denmark)

    Eliasen, Marie; Becker, Ulrik; Grønbæk, Morten;

    2014-01-01

    The aim of the study was to quantify alcohol-attributable and -preventable mortality, totally and stratified on alcohol consumption in Denmark 2010, and to estimate alcohol-related mortality assuming different scenarios of changes in alcohol distribution in the population. We estimated alcohol......-attributable and -preventable fractions based on relative risks of conditions causally associated with alcohol from meta-analyses and information on alcohol consumption in Denmark obtained from 14,458 participants in the Danish National Health Survey 2010 and corrected for adult per capita consumption. Cause-specific mortality...... data were obtained from the Danish Register of Causes of Death. In total, 1,373 deaths among women (5.0 % of all deaths) and 2,522 deaths among men (9.5 % of all deaths) were attributable to alcohol, while an estimated number of 765 (2.8 %) and 583 (2.2 %) deaths were prevented by alcohol...

  2. Alcohol drinking pattern and risk of alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Askgaard, Gro; Grønbæk, Morten; Kjær, Mette Skalshøi;

    2015-01-01

    BACKGROUND & AIMS: Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. METHODS: We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993......-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. RESULTS......: We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4 days/week. Alcohol amount in recent age periods (40-49 and 50...

  3. Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

    Science.gov (United States)

    Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

    2014-01-01

    Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented.

  4. FaQR, required for the biosynthesis of the strawberry flavor compound 4-hydroxy-2,5-dimethyl-3(2H)-furanone, encodes an enone oxidoreductase.

    Science.gov (United States)

    Raab, Thomas; López-Ráez, Juan Antonio; Klein, Dorothée; Caballero, Jose Luis; Moyano, Enriqueta; Schwab, Wilfried; Muñoz-Blanco, Juan

    2006-04-01

    The flavor of strawberry (Fragaria x ananassa) fruit is dominated by an uncommon group of aroma compounds with a 2,5-dimethyl-3(H)-furanone structure. We report the characterization of an enzyme involved in the biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF; Furaneol), the key flavor compound in strawberries. Protein extracts were partially purified, and the observed distribution of enzymatic activity correlated with the presence of a single polypeptide of approximately 37 kD. Sequence analysis of two peptide fragments showed total identity with the protein sequence of a strongly ripening-induced, auxin-dependent putative quinone oxidoreductase, Fragaria x ananassa quinone oxidoreductase (FaQR). The open reading frame of the FaQR cDNA consists of 969 bp encoding a 322-amino acid protein with a calculated molecular mass of 34.3 kD. Laser capture microdissection followed by RNA extraction and amplification demonstrated the presence of FaQR mRNA in parenchyma tissue of the strawberry fruit. The FaQR protein was functionally expressed in Escherichia coli, and the monomer catalyzed the formation of HDMF. After chemical synthesis and liquid chromatography-tandem mass spectrometry analysis, 4-hydroxy-5-methyl-2-methylene-3(2H)-furanone was confirmed as a substrate of FaQR and the natural precursor of HDMF. This study demonstrates the function of the FaQR enzyme in the biosynthesis of HDMF as enone oxidoreductase and provides a foundation for the improvement of strawberry flavor and the biotechnological production of HDMF.

  5. Exploring the 49-kDa subunit as part of the catalytic core of complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica

    OpenAIRE

    Grgic, Ljuban

    2004-01-01

    Ligands of Iron-Sulphur Cluster N2: In this work the ubiquinone reducing catalytic core of NADH:ubiquinone oxidoreductase (complex I) from Y. lipolytica was studied by a series of point mutations replacing conserved histidines or arginines in the 49-kDa subunit. Although the missing 4th ligand of cluster N2 could not be found in the 49-kDa subunit of complex I, it was clearly demonstrated that iron-sulphur cluster N2 resides directly on the interface between the PSST and 49-kDa subunits. The ...

  6. ns-μs Time-Resolved Step-Scan FTIR of ba3 Oxidoreductase from Thermus thermophilus: Protonic Connectivity of w941-w946-w927

    Science.gov (United States)

    Nicolaides, Antonis; Soulimane, Tewfik; Varotsis, Constantinos

    2016-01-01

    Time-resolved step-scan FTIR spectroscopy has been employed to probe the dynamics of the ba3 oxidoreductase from Thermus thermophilus in the ns-μs time range and in the pH/pD 6–9 range. The data revealed a pH/pD sensitivity of the D372 residue and of the ring-A propionate of heme a3. Based on the observed transient changes a model in which the protonic connectivity of w941-w946-927 to the D372 and the ring-A propionate of heme a3 is described. PMID:27690021

  7. Alcohol combustion chemistry

    KAUST Repository

    Sarathy, Mani

    2014-10-01

    Alternative transportation fuels, preferably from renewable sources, include alcohols with up to five or even more carbon atoms. They are considered promising because they can be derived from biological matter via established and new processes. In addition, many of their physical-chemical properties are compatible with the requirements of modern engines, which make them attractive either as replacements for fossil fuels or as fuel additives. Indeed, alcohol fuels have been used since the early years of automobile production, particularly in Brazil, where ethanol has a long history of use as an automobile fuel. Recently, increasing attention has been paid to the use of non-petroleum-based fuels made from biological sources, including alcohols (predominantly ethanol), as important liquid biofuels. Today, the ethanol fuel that is offered in the market is mainly made from sugar cane or corn. Its production as a first-generation biofuel, especially in North America, has been associated with publicly discussed drawbacks, such as reduction in the food supply, need for fertilization, extensive water usage, and other ecological concerns. More environmentally friendly processes are being considered to produce alcohols from inedible plants or plant parts on wasteland. While biofuel production and its use (especially ethanol and biodiesel) in internal combustion engines have been the focus of several recent reviews, a dedicated overview and summary of research on alcohol combustion chemistry is still lacking. Besides ethanol, many linear and branched members of the alcohol family, from methanol to hexanols, have been studied, with a particular emphasis on butanols. These fuels and their combustion properties, including their ignition, flame propagation, and extinction characteristics, their pyrolysis and oxidation reactions, and their potential to produce pollutant emissions have been intensively investigated in dedicated experiments on the laboratory and the engine scale

  8. Adaptive hepatic and intestinal alterations in mice after deletion of NADPH-cytochrome P450 Oxidoreductase (Cpr) in hepatocytes.

    Science.gov (United States)

    Cheng, Xingguo; Gu, Jun; Klaassen, Curtis D

    2014-11-01

    Cytochrome P450 enzymes (P450) play an important role in first-pass metabolism in both the intestine and liver. NADPH-cytochrome P450 oxidoreductase (Cpr) is an essential electron transfer protein required for microsomal P450 activity. Mice with conditional knockout of Cpr in hepatocytes develop normally and survive even with complete loss of liver microsomal P450 activity. Our current studies were performed to determine whether alternative drug-metabolizing pathways increase in an attempt to maintain whole-body homeostasis. In addition to the liver, Cpr is mainly expressed in tissues such as lung, kidney, and gastrointestinal tract. In livers of H-Cpr-null mice, there is a marked increase in mRNA expression of phase I enzymes (Aldh1a1, 1a7, 3a2; Ces1b2, 2a6, and 2a12), antioxidant enzymes (Ho-1, Nqo1, and epoxide hydrolase), phase II enzymes (Ugt1a9; Gsta1/2, m3, m4, m6, t1, and t3; and Sult1a1 and 1d1), and drug transporters (Oatp1a4, Oct3, Mate1, Mdr1a, and Mrp3 and 4). In addition, glucuronide-conjugated bilirubin concentrations are doubled in serum of H-Cpr-null mice. Both constitutive androstane receptor (CAR) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein in nuclei are higher in the livers of H-Cpr-null mice, indicating that CAR and Nrf2 are activated. In the small intestine of H-Cpr-null mice, mRNA expression of Cyp3a11 and Mdr1a, two genes critical for intestinal first-pass metabolism, are markedly up-regulated. In addition, nutrient (Pept1) and cholesterol (Npc1l1) transporters are induced in the small intestine of H-Cpr-null mice. In conclusion, in H-Cpr-null mice, adaptive regulation of alternative detoxification genes in liver and small intestine appear to partially compensate for the loss of microsomal P450 function in liver.

  9. Alcohol Alert: Alcohol's Damaging Effects on the Brain

    Science.gov (United States)

    ... R.; et al. Gender differences in moderate drinking effects. Alcohol Research & Health 23:55–64, 1999. (5) Loft, S. ; ... A.; and Sullivan, E. Sex differences in the effects of alcohol on brain structure. American Journal of Psychiatry 158: ...

  10. Alcoholism and Alcohol Abuse - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Alcoholism and Alcohol Abuse URL of this page: https://medlineplus.gov/languages/alcoholismandalcoholabuse.html Other topics A-Z A B ...

  11. 78 FR 21615 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-11

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial ] Review... Foster, Ph.D., Scientific Review Administrator, National Institutes on Alcohol Abuse &...

  12. 78 FR 38353 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-06-26

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis Panel; Review of Applications on HIV- AIDS/Alcohol Comparative Effectiveness & Implementation...

  13. Psychoanalytic Treatment of Psychological Addiction to Alcohol (Alcohol Abuse)

    OpenAIRE

    Johnson, Brian

    2011-01-01

    The DSM-V Committee plans to abolish the distinction between Alcohol Abuse and Alcohol Dependence (dsm5.org). The author presents a case report as a proof of concept that this distinction should be retained. The author has asserted that Alcohol Abuse is a purely psychological addiction, while Alcohol Dependence involves capture of the ventral tegmental dopaminergic SEEKING system (Johnson, 2003). In psychological addiction the brain can be assumed to function normally, and ordinary psychoanal...

  14. A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence

    Science.gov (United States)

    Reardon-Robinson, Melissa E.; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2016-01-01

    Summary The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. PMID:26294390

  15. Directed Evolution and Resolution Mechanism of 1, 3-Propanediol Oxidoreductase from Klebsiella pneumoniae toward Higher Activity by Error-Prone PCR and Bioinformatics.

    Directory of Open Access Journals (Sweden)

    Wei Jiang

    Full Text Available 1, 3-propanediol oxidoreductase (PDOR is a key enzyme in glycerol bioconversion to 1,3-propanediol (1, 3-PD which is a valuable chemical and one of the six new petrochemical products. We used error-prone PCR and activity screening to identify mutants of Klebsiella pneumoniae (K. pneumoniae PDOR with improved activity. The activity of one of the identified mutants, PDOR'-24, which includes a single mutation, A199S, was 48 U/mg, 4.9 times that of the wild-type enzyme. Molecular docking was performed to analyze the identified mutants; and amino acids S103, H271, N366, D106, N262 and D364 were predicted to bond with NADH. The origins of the improved activity of PDOR'-24, as well as three other mutants were analyzed by simulating the interaction mechanism of the mutants with the substrate and coenzyme, respectively. This research provides useful information about the use of safranine O plate screening for the directed evolution of oxidoreductases, identifies interesting sites for improving PDOR activity, and demonstrates the utility of using molecular docking to analyze the interaction mechanism of the mutants with the substrate and coenzyme, respectively.

  16. Biotransformation of pineapple juice sugars into dietetic derivatives by using a cell free oxidoreductase from Zymomonas mobilis together with commercial invertase.

    Science.gov (United States)

    Aziz, M G; Michlmayr, H; Kulbe, K D; Del Hierro, A M

    2011-01-01

    An easy procedure for cell free biotransformation of pineapple juice sugars into dietetic derivatives was accomplished using a commercial invertase and an oxidoreductase from Zymomonas mobilis. First, pineapple juice sucrose was quantitatively converted into glucose and fructose by invertase, thus increasing the concentration of each monosaccharide in the original juice to almost twice. In a second step, glucose-fructose oxidoreductase (GFOR) transformed glucose into gluconolactone, and fructose into the low calorie sweetener sorbitol. The advantage of using GFOR is simultaneous reduction of fructose and oxidation of glucose, allowing the continuous regeneration of the essential coenzyme NADP(H), that is tightly bound to the enzyme. The yield of GFOR catalyzed sugar conversion depends on initial pH and control of pH during the reaction. At optimal conditions (pH control at 6.2) a maximum of 80% (w/v) sugar conversion was obtained. Without pH control, GFOR is inactivated rapidly due to gluconic acid formation. Therefore, conversion yields are relatively low at the natural pH of pineapple juice. The application of this process might be more advantageous on juices of other tropical fruits (papaya, jackfruit, mango) due to their naturally given higher pH. PMID:22112775

  17. The Effects of Xanthine Oxidoreductase Inhibitors on Oxidative Stress Markers following Global Brain Ischemia Reperfusion Injury in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Masahiro Yamaguchi

    Full Text Available We demonstrated that 3-nitrotyrosine and 4-hydroxy-2-nonenal levels in mouse brain were elevated from 1 h until 8 h after global brain ischemia for 14 min induced with the 3-vessel occlusion model; this result indicates that ischemia reperfusion injury generated oxidative stress. Reactive oxygen species production was observed not only in the hippocampal region, but also in the cortical region. We further evaluated the neuroprotective effect of xanthine oxidoreductase inhibitors in the mouse 3-vessel occlusion model by analyzing changes in the expression of genes regulated by the transcription factor nuclear factor-kappa B (including pro-inflammatory cytokines interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α, matrix metalloproteinase-9 and intercellular adhesion molecules-1. Administration of allopurinol resulted in a statistically significant decrease in IL-1β and TNF-α mRNA expression, whereas febuxostat had no significant effect on expression of these genes; nevertheless, both inhibitors effectively reduced serum uric acid concentration. It is suggested that the neuroprotective effect of allopurinol is derived not from inhibition of reactive oxygen species production by xanthine oxidoreductase, but rather from a direct free-radical-scavenging effect.

  18. Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3α-Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive of GABAA Receptors Involvement

    Directory of Open Access Journals (Sweden)

    Roberto Yunes

    2015-01-01

    Full Text Available There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegenerative diseases. By using a model of hemiparkinsonism in male rats, injection of the neurotoxic 6-OHDA in left striatum, we studied progesterone’s effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to find potential explanatory mechanisms, we studied expression and activity of nigrostriatal 3α-hydroxysteroid oxidoreductase, the enzyme that catalyzes progesterone to its active metabolite allopregnanolone. Coherently, we tested allopregnanolone for a possible neuromodulatory effect on rotational behavior. Also, since allopregnanolone is known as a GABAA modulator, we finally examined the action of GABAA antagonist bicuculline. We found that progesterone, in addition to an apparent neuroprotective effect, also increased ipsilateral expression and activity of 3α-hydroxysteroid oxidoreductase. It was interesting to note that ipsilateral administration of allopregnanolone reversed a clear sign of motor neurodegeneration, that is, contralateral rotational behavior. A possible GABAA involvement modulated by allopregnanolone was shown by the blocking effect of bicuculline. Our results suggest that early administration of progesterone possibly activates genomic mechanisms that promote neuroprotection subchronically. This, in turn, could be partially mediated by fast, nongenomic, actions of allopregnanolone acting as an acute modulator of GABAergic transmission.

  19. Alcoholic Lung Disease

    OpenAIRE

    Kershaw, Corey D.; Guidot, David M.

    2008-01-01

    In addition to its well-known association with lung infection (i.e., pneumonia), alcohol abuse now is recognized as an independent factor that increases by three- to four-fold the incidence of the acute respiratory distress syndrome, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in...

  20. Alcohol, cannabis y accidentalidad

    OpenAIRE

    Olave Porrua, Leticia; Matos Larrinaga, Jesús; Salguero Noguera, Martín; Ramos Cejudo, Juan; Mae Wood, Cristina; Iruarrizaga Díez, Itziar

    2011-01-01

    Se ha desarrollado este trabajo de revisión con el objetivo de concentrar los últimos avances en investigación del consumo de alcohol y cannabis y su infl uencia en la conducción. Se realizaron tres búsquedas sistemáticas en la base de datos Psycinfo, introduciendo las palabras clave 'alcohol' AND 'traffi c'y 'cannabis' AND 'traffi c', restringida a los últimos cinco años (de enero de 2006 a diciembre de 2010). El presente trabajo incluye los datos más relevantes sobre prevalen...

  1. Information on Blood Alcohol Concentration: Evaluation of Two Alcohol Nomograms.

    Science.gov (United States)

    Werch, Chudley E.

    1988-01-01

    Compared utility of two common alcohol nomograms on impacting decisions regarding drinking, driving after drinking, knowledge of relationship between personal alcohol consumption and the legal level of intoxication, and consumer evaluation measures, to utility of alcohol information warning card. Nomograms were no more effective than cards warning…

  2. Relationship between Alcohol Consumption and Alcohol Problems in Young Adults.

    Science.gov (United States)

    Werch, Chudley E.; And Others

    1987-01-01

    Examined relationship among alcohol problems and alcohol consumption variables in 410 college students. Total alcohol-related problems, drinking and driving problems, and school problems increased significantly when subjects drank moderately. Physical illness problems increased during light drinking, while interpersonal and legal problems…

  3. Alcohol consumption, alcohol dehydrogenase 3 polymorphism, and colorectal adenomas

    NARCIS (Netherlands)

    Tiemersma, E.W.; Wark, P.A.; Ocké, M.C.; Bunschoten, A.; Otten, M.H.; Kok, F.J.; Kampman, E.

    2003-01-01

    Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism.

  4. Men's Health: Alcohol and Drug Abuse

    Science.gov (United States)

    ... This information in Spanish ( en español ) Alcohol and drug abuse More information on alcohol and drug abuse Alcohol ... Return to top More information on Alcohol and drug abuse Explore other publications and websites Consequences of the ...

  5. Alcohol and Public Health: Frequently Asked Questions

    Science.gov (United States)

    ... it okay to drink when pregnant? What is alcohol? Ethyl alcohol, or ethanol, is an intoxicating ingredient ... sugars, and starches. Top of Page How does alcohol affect a person? Alcohol affects every organ in ...

  6. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Fede, Giuseppe; Germani, Giacomo; Gluud, Christian;

    2011-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  7. Alcohol use and safe drinking

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001944.htm Alcohol use and safe drinking To use the sharing features on this page, please enable JavaScript. Alcohol use involves drinking beer, wine, or hard liquor. ...

  8. Alcohol dependence--classificatory considerations.

    Science.gov (United States)

    Lesch, O M; Ades, J; Badawy, A; Pelc, I; Sasz, H

    1993-01-01

    The term alcoholism or alcohol dependence has acquired a broad range of meanings. The Plinius Maior Society herewith presents new classificatory considerations and suggests additional recording of special dimensions according to the individual hypothesis and design of a study.

  9. The bifunctional aldehyde-alcohol dehydrogenase controls ethanol and acetate production in Entamoeba histolytica under aerobic conditions.

    Science.gov (United States)

    Pineda, Erika; Encalada, Rusely; Olivos-García, Alfonso; Néquiz, Mario; Moreno-Sánchez, Rafael; Saavedra, Emma

    2013-01-16

    By applying metabolic control analysis and inhibitor titration we determined the degree of control (flux control coefficient) of pyruvate:ferredoxin oxidoreductase (PFOR) and bifunctional aldehyde-alcohol dehydrogenase (ADHE) over the fluxes of fermentative glycolysis of Entamoeba histolytica subjected to aerobic conditions. The flux-control coefficients towards ethanol and acetate formation determined for PFOR titrated with diphenyleneiodonium were 0.07 and 0.09, whereas for ADHE titrated with disulfiram were 0.33 and -0.19, respectively. ADHE inhibition induced significant accumulation of glycolytic intermediates and lower ATP content. These results indicate that ADHE exerts significant flux-control on the carbon end-product formation of amoebas subjected to aerobic conditions. PMID:23201265

  10. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2002-01-01

    Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease.......Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease....

  11. Photobiomodulation on alcohol induced dysfunction

    Science.gov (United States)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  12. Alcohol and American Indian Students.

    Science.gov (United States)

    Boyce, George A.

    The growing problem of teenage drinking and alcoholism in the United States, especially among Indian segments of society, increases the necessity for adequate education concerning alcoholism. This document is prepared for the Bureau of Indian Affairs (BIA) schools to acquaint Indian students with social concepts of alcohol outside their cultural…

  13. Geriatric Alcoholism and Drug Abuse

    Science.gov (United States)

    Schuckit, Marc A.

    1977-01-01

    This paper reviews the literature and presents new data on alcohol and drug problems in older individuals. Drug abusers include users of opiates, inadvertent misusers, and deliberate abusers of nonopiates. Two to 10 percent of the elderly are alcoholic, and these are usually individuals beginning alcohol abuse after age 40. (Author)

  14. Counseling Young Children of Alcoholics.

    Science.gov (United States)

    Brake, Kathryn J.

    1988-01-01

    Provides a rationale for services to children of alcoholics and describes school-based interventions to help these children. Asserts that schools are the logical setting for providing knowledge, skills, and support to help children of alcoholics understand the dysfunctional effects of familial alcoholism. Offers suggestions for school counselors…

  15. Alcohol, marihuana and youth

    OpenAIRE

    KREJČOVÁ, Iveta

    2012-01-01

    The subject of this work is misusing alcohol and illicit addicting substances (primarily marijuana) by students at high schools. The research was done at specifically chosen high school by questionnaires, that helped to uncover student?s experiences with illicit addicting substances.

  16. Saying No to Alcohol.

    Science.gov (United States)

    Abbey, Nancy; Wagman, Ellen

    This teacher guide is part of a series of three interactive books on tobacco, alcohol, and marijuana; three informational books containing parallel content; and three teacher guides designed to give students in grades five through eight practice in using the information and skills presented in the books. The guide provides teachers with a…

  17. Children of Alcoholics

    Science.gov (United States)

    ... at home: Failure in school; truancy Lack of friends; withdrawal from classmates Delinquent behavior, such as stealing or violence Frequent physical complaints, such as headaches or stomachaches Abuse of drugs or alcohol; or Aggression towards other children Risk taking behaviors Depression or ...

  18. Alcohol use following an alcohol challenge and a brief intervention among alcohol-dependent individuals

    OpenAIRE

    Bacio, GA; Lunny, KF; Webb, JN; Ray, LA

    2014-01-01

    Background and Objectives The study examined the effects of an alcohol challenge on naturalistic drinking among alcohol-dependent individuals and explored brief motivational interviewing (MI) as a potential intervention for these participants. Method Alcohol-dependent individuals (n = 32, eight females) completed the intake assessment, alcohol challenge, one MI session, and 1-month follow-up (87.5% retention) where they completed measures of drinking and motivation for change. Results As expe...

  19. Body composition in detoxified alcoholics.

    Science.gov (United States)

    York, J L; Pendergast, D E

    1990-04-01

    Body composition was evaluated in healthy detoxified alcoholics (aged 20-39) and lifestyle controls, with the expectation that prolonged, excessive consumption of alcohol may bring about nutritional or toxicologic alterations in the relationship between body fat and lean body mass. Body fat was assessed by measurements of skin-fold thickness and by means of bioelectric impedance methodology. No noteworthy differences were observed between alcoholics and controls with regard to the relationship between lean body mass and body fat or in the relationship between extracellular and intracellular water. It would appear that 15-20 years of heavy alcohol consumption does not necessarily alter body composition in healthy, young alcoholics. PMID:2190482

  20. Preoperative alcoholism and postoperative morbidity

    DEFF Research Database (Denmark)

    Tonnesen, H; Kehlet, H

    1999-01-01

    BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

  1. Alcohol and male reproductive health

    DEFF Research Database (Denmark)

    Jensen, Tina Kold; Swan, Shanna; Jørgensen, Niels;

    2014-01-01

    by type of alcohol. However, we found a linear association between total alcohol consumption and total or free testosterone in both groups of men. Young and fertile men who consumed >20 units of alcohol per week had, respectively, 24.6 pmol/l (95% confidence interval 16.3-32.9) and 19.7 pmol/l (7......STUDY QUESTION: Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe? SUMMARY ANSWER: Moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher...... serum testosterone levels. WHAT IS KNOWN ALREADY: High alcohol intake has been associated with a wide range of diseases. However, few studies have examined the correlation between alcohol and reproductive function and most have been conducted in selected populations of infertile men or have a small...

  2. Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis

    Science.gov (United States)

    Baker, Susan S.; Baker, Robert D.; Liu, Wensheng; Nowak, Norma J.; Zhu, Lixin

    2010-01-01

    Background Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals. Methodology/Principal Findings To investigate whether alcohol is involved in the pathogenesis of NASH, the expression of inflammation, fibrosis and alcohol metabolism related genes in the liver tissues of NASH patients and normal controls (NCs) were examined by microarray (NASH, n = 7; NC, n = 4) and quantitative real-time PCR (NASH, n = 6; NC, n = 6). Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1 and ADH4 in NASH livers (NASH, n = 9; NC, n = 4). Conclusions/Significance The augmented activity of all the available genes of the pathways for alcohol catabolism suggest that 1) alcohol concentration was elevated in the circulation of NASH patients; 2) there was a high priority for the NASH livers to scavenge alcohol from the circulation. Our data is the first human evidence that suggests alcohol may contribute to the development of NAFLD. PMID:20221393

  3. Role of alcohol metabolism in non-alcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Susan S Baker

    Full Text Available BACKGROUND: Non-alcoholic steatohepatitis (NASH is a serious form of non-alcoholic fatty liver disease (NAFLD, associated with obesity and insulin resistance. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether alcohol is involved in the pathogenesis of NASH, the expression of inflammation, fibrosis and alcohol metabolism related genes in the liver tissues of NASH patients and normal controls (NCs were examined by microarray (NASH, n = 7; NC, n = 4 and quantitative real-time PCR (NASH, n = 6; NC, n = 6. Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1 and ADH4 in NASH livers (NASH, n = 9; NC, n = 4. CONCLUSIONS/SIGNIFICANCE: The augmented activity of all the available genes of the pathways for alcohol catabolism suggest that 1 alcohol concentration was elevated in the circulation of NASH patients; 2 there was a high priority for the NASH livers to scavenge alcohol from the circulation. Our data is the first human evidence that suggests alcohol may contribute to the development of NAFLD.

  4. Unexpected properties of NADP-dependent secondary alcohol dehydrogenase (ADH-1) in Trichomonas vaginalis and other microaerophilic parasites.

    Science.gov (United States)

    Leitsch, David; Williams, Catrin F; Lloyd, David; Duchêne, Michael

    2013-07-01

    Our previous observation that NADP-dependent secondary alcohol dehydrogenase (ADH-1) is down-regulated in metronidazole-resistant Trichomonas vaginalis isolates prompted us to further characterise the enzyme. In addition to its canonical enzyme activity as a secondary alcohol dehydrogenase, a pronounced, so far unknown, background NADPH-oxidising activity in absence of any added substrate was observed when the recombinant enzyme or T. vaginalis extract were used. This activity was strongly enhanced at low oxygen concentrations. Unexpectedly, all functions of ADH-1 were efficiently inhibited by coenzyme A which is a cofactor of a number of key enzymes in T. vaginalis metabolism, i.e. pyruvate:ferredoxin oxidoreductase (PFOR). These observations could be extended to Entamoeba histolytica and Tritrichomonas foetus, both of which have a homologue of ADH-1, but not to Giardia lamblia which lacks an NADP-dependent secondary alcohol dehydrogenase. Although we could not identify the substrate of the observed background activity, we propose that ADH-1 functions as a major sink for NADPH in microaerophilic parasites at low oxygen tension.

  5. Unexpected properties of NADP-dependent secondary alcohol dehydrogenase (ADH-1) in Trichomonas vaginalis and other microaerophilic parasites.

    Science.gov (United States)

    Leitsch, David; Williams, Catrin F; Lloyd, David; Duchêne, Michael

    2013-07-01

    Our previous observation that NADP-dependent secondary alcohol dehydrogenase (ADH-1) is down-regulated in metronidazole-resistant Trichomonas vaginalis isolates prompted us to further characterise the enzyme. In addition to its canonical enzyme activity as a secondary alcohol dehydrogenase, a pronounced, so far unknown, background NADPH-oxidising activity in absence of any added substrate was observed when the recombinant enzyme or T. vaginalis extract were used. This activity was strongly enhanced at low oxygen concentrations. Unexpectedly, all functions of ADH-1 were efficiently inhibited by coenzyme A which is a cofactor of a number of key enzymes in T. vaginalis metabolism, i.e. pyruvate:ferredoxin oxidoreductase (PFOR). These observations could be extended to Entamoeba histolytica and Tritrichomonas foetus, both of which have a homologue of ADH-1, but not to Giardia lamblia which lacks an NADP-dependent secondary alcohol dehydrogenase. Although we could not identify the substrate of the observed background activity, we propose that ADH-1 functions as a major sink for NADPH in microaerophilic parasites at low oxygen tension. PMID:23578856

  6. Dry alcohol production plant

    Directory of Open Access Journals (Sweden)

    Stanković Mirjana S.

    2003-01-01

    Full Text Available The IGPC Engineering Department designed basic projects for dry alcohol production plant, using technology developed in the IGPC laboratories. Several projects were completed: technological, machine, electrical, automation. On the basis of these projects a production plant with a capacity of 40 m3/y was manufactured, at "Zorka Pharma", Šabac in 1995-1996. The product meets all quality demands, as well as environmental regulations. The dry alcohol production process is fully automatized. There is no waste in the process, neither gaseous, nor liquid. The chosen process provides safe operation according to temperature regime and resistance in the pipes, air purification columns and filters. Working at increased pressure is suitable for evaporation and condensation at increased temperatures. The production process can be controlled manually, which is necessary during start-up, and repairs.

  7. Alcoholism in the Elderly

    OpenAIRE

    Cohen, Saul

    1988-01-01

    This article concentrates on the identification confrontation, and treatment of the elderly with late-onset alcohol-abuse problems. The author reviews signs and symptoms that are common both to the aging process and to late-onset problem drinking. He also provides a list of laboratory “markers” that may be helpful for the diagnosis and follow-up of this not infrequent problem.

  8. Method for recovering alcohol

    Energy Technology Data Exchange (ETDEWEB)

    Dahlstrom, R.A.; Rubin, J.N.

    1980-04-17

    In this method for extraction of alcohol from fermented material, insoluble organic matter is first removed before the ferment enters the distillation column and tried spent grains then recovered by drying under pressure. Excess steam from the drying stage is used to heat the distillation column. In addition, excess water vapour produced as a result of further heating by head vapour from the first distillation column, is drawn off from the evaporation step, condensed and fed into the distillation columns and evaporation step.

  9. Adolescent alcohol use

    DEFF Research Database (Denmark)

    Bendtsen, Pernille; Damsgaard, Mogens Trab; Huckle, Taisia;

    2014-01-01

    AIMS: To analyse how adolescent drunkenness and frequency of drinking were associated with adult drinking patterns and alcohol control policies. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional survey data on 13- and 15-year-olds in 37 countries who participated in the Health Behaviour in School......-Aged Children (HBSC) Study in 2010 (n = 144 788) were linked to national-level indicators on alcohol control policies and adult drinking patterns. MEASUREMENTS: Outcome measures were self-reported weekly drinking and life-time drunkenness (drunk once or more). Data were analysed using multi-level logistic...... regression models. FINDINGS: In the mutually adjusted models, adolescent drunkenness was associated significantly with high adult alcohol consumption [odds ratio (OR) = 3.15 among boys, 95% confidence interval (CI) = 2.13-4.64, OR girls = 2.44, CI = 1.57-3.80] and risky drinking patterns in the adult...

  10. Nanosecond ligand migration and functional protein relaxation in ba3 oxidoreductase: Structures of the B0, B1 and B2 intermediate states.

    Science.gov (United States)

    Nicolaides, Antonis; Soulimane, Tewfik; Varotsis, Constantinos

    2016-09-01

    Nanosecond time-resolved step-scan FTIR spectroscopy (nTRS (2) -FTIR) has been applied to literally probe the active site of the carbon monoxide (CO)-bound thermophilic ba3 heme-copper oxidoreductase as it executes its function. The nTRS (2) - snapshots of the photolysed heme a3 Fe-CO/CuB species captured a "transition state" whose side chains prevent the photolysed CO to enter the docking cavity. There are three sets of ba3 photoproduct bands of docked CO with different orientation exhibiting different kinetics. The trajectories of the "docked" CO at 2122, 2129 and 2137cm(-1) is referred to in the literature as B2, B1 and B0 intermediate states, respectively. The present data provided direct evidence for the role of water in controlling ligand orientation in an intracavity protein environment. PMID:27207588

  11. Wiring of the aldehyde oxidoreductase PaoABC to electrode surfaces via entrapment in low potential phenothiazine-modified redox polymers.

    Science.gov (United States)

    Pinyou, Piyanut; Ruff, Adrian; Pöller, Sascha; Alsaoub, Sabine; Leimkühler, Silke; Wollenberger, Ulla; Schuhmann, Wolfgang

    2016-06-01

    Phenothiazine-modified redox hydrogels were synthesized and used for the wiring of the aldehyde oxidoreductase PaoABC to electrode surfaces. The effects of the pH value and electrode surface modification on the biocatalytic activity of the layers were studied in the presence of vanillin as the substrate. The enzyme electrodes were successfully employed as bioanodes in vanillin/O2 biofuel cells in combination with a high potential bilirubin oxidase biocathode. Open circuit voltages of around 700 mV could be obtained in a two compartment biofuel cell setup. Moreover, the use of a rather hydrophobic polymer with a high degree of crosslinking sites ensures the formation of stable polymer/enzyme films which were successfully used as bioanode in membrane-less biofuel cells. PMID:26775204

  12. Alcohol and the work place

    CERN Multimedia

    2004-01-01

    The CERN Medical Service has observed an increase in the number of personnel suffering from alcohol-related problems in recent years, in spite of the implementation of stricter regulations concerning the consumption of alcohol on the site. The causes of alcohol-related problems are often complex and many-faceted. A family history of alcohol abuse can be a cofactor in excessive drinking. The effects on a person's work are not negligible and should not be ignored. "Alcohol and the work place" is the third part of a campaign designed to raise awareness of the risks of alcohol consumption, which has already dealt with "alcohol and health" and "alcohol and road safety".Many employers have taken steps to confront the problem, and CERN launched a campaign to help its employees suffering from alcohol-related problems over ten years ago. A standing SCC sub-group on the prevention of alcoholism has been set up and Operational Circular No. 8, which defines the role and responsibilities of all parties concerned in the m...

  13. [Current peculiarities of alcoholic psychosis].

    Science.gov (United States)

    Aleksin, D S; Egorov, A Iu

    2011-01-01

    The follow-up study of alcoholic psychoses in male patients admitted to a clinical department of a psychiatric hospital in 2005-2007 was carried out. Patients with alcoholic psychoses made up from 15 to 30% of all patients. The number of psychosis had seasonal variations with the elevations in spring and autumn, peaks in January, lune and October. Alcoholic delirium morbidity made up from 69 to 82% of the total number of alcoholic psychoses, alcoholic hallucinosis varied from 14 to 27%. Other forms were presented by single cases. In alcoholic delirium hallucinations had brighter, sated character. The most specific were visual hallucinations in the form of zoohallucinations, hallucinations of an oral cavity ("sensation of threads, hair etc"). The most often observable characters were "extraneous people, animal, demons". In alcoholic hallucinosis, verbal contrast hallucinations, making comment hallucinations, visual illusions were most frequent. The family history of mental disorders and alcoholism was noted in 30% of patients with alcoholic psychosis. The probability of occurrence of alcoholic psychoses depended on the quality of consumed drinks. The presence of a cranial-brain injury in the anamnesis considerably aggravated the disease forecast and increased the risk of seizure syndrome. PMID:22611692

  14. Roles of the sodium-translocating NADH:quinone oxidoreductase (Na+-NQR) on vibrio cholerae metabolism, motility and osmotic stress resistance.

    Science.gov (United States)

    Minato, Yusuke; Fassio, Sara R; Kirkwood, Jay S; Halang, Petra; Quinn, Matthew J; Faulkner, Wyatt J; Aagesen, Alisha M; Steuber, Julia; Stevens, Jan F; Häse, Claudia C

    2014-01-01

    The Na+ translocating NADH:quinone oxidoreductase (Na+-NQR) is a unique respiratory enzyme catalyzing the electron transfer from NADH to quinone coupled with the translocation of sodium ions across the membrane. Typically, Vibrio spp., including Vibrio cholerae, have this enzyme but lack the proton-pumping NADH:ubiquinone oxidoreductase (Complex I). Thus, Na+-NQR should significantly contribute to multiple aspects of V. cholerae physiology; however, no detailed characterization of this aspect has been reported so far. In this study, we broadly investigated the effects of loss of Na+-NQR on V. cholerae physiology by using Phenotype Microarray (Biolog), transcriptome and metabolomics analyses. We found that the V. cholerae ΔnqrA-F mutant showed multiple defects in metabolism detected by Phenotype Microarray. Transcriptome analysis revealed that the V. cholerae ΔnqrA-F mutant up-regulates 31 genes and down-regulates 55 genes in both early and mid-growth phases. The most up-regulated genes included the cadA and cadB genes, encoding a lysine decarboxylase and a lysine/cadaverine antiporter, respectively. Increased CadAB activity was further suggested by the metabolomics analysis. The down-regulated genes include sialic acid catabolism genes. Metabolomic analysis also suggested increased reductive pathway of TCA cycle and decreased purine metabolism in the V. cholerae ΔnqrA-F mutant. Lack of Na+-NQR did not affect any of the Na+ pumping-related phenotypes of V. cholerae suggesting that other secondary Na+ pump(s) can compensate for Na+ pumping activity of Na+-NQR. Overall, our study provides important insights into the contribution of Na+-NQR to V. cholerae physiology.

  15. Circulating Cytokines as Biomarkers of Alcohol Abuse and Alcoholism

    OpenAIRE

    Rajeshwara N. Achur; Freeman, Willard M.; Vrana, Kent E.

    2009-01-01

    There are currently no consistent objective biochemical markers of alcohol abuse and alcoholism. Development of reliable diagnostic biomarkers that permit accurate assessment of alcohol intake and patterns of drinking is of prime importance to treatment and research fields. Diagnostic biomarker development in other diseases has demonstrated the utility of both open, systems biology, screening for biomarkers and more rational focused efforts on specific biomolecules or families of biomolecules...

  16. Diagnostic challenges in alcohol use disorder and alcoholic liver disease

    OpenAIRE

    Vonghia, Luisa; Michielsen, Peter; Dom, Geert; Francque, Sven

    2014-01-01

    Alcohol use disorders represent a heterogeneous spectrum of clinical manifestations that have been defined by the Diagnostic and Statistical Manual of Mental Disorders-5. Excessive alcohol intake can lead to damage of various organs, including the liver. Alcoholic liver disease includes different injuries ranging from steatosis to cirrhosis and implicates a diagnostic assessment of the liver disease and of its possible complications. There is growing interest in the possible different tools f...

  17. Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

    OpenAIRE

    Branas, Charles C; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

    2011-01-01

    A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurr...

  18. Alcohol-specific parenting, adolescent alcohol use and the mediating effect of adolescent alcohol-related cognitions

    NARCIS (Netherlands)

    Mares, S.H.W.; Lichtwarck-Aschoff, A.; Engels, R.C.M.E.

    2013-01-01

    Objectives : Previous research indicated that alcohol-specific parenting is an important precursor of adolescent alcohol use, but failed to define the underlying mechanism. Based on social cognitive theory, alcohol-related cognitions such as alcohol refusal self-efficacy and alcohol-related expectan

  19. Mortality from alcohol consumption and alcohol use disorder

    DEFF Research Database (Denmark)

    Lundin, Andreas; Mortensen, Laust Hvas

    2015-01-01

    BACKGROUND: To examine the relationship of alcohol consumption, alcohol use disorder and mortality. METHOD: A cohort of 4316 male former Vietnam-era US army personnel participating in telephone survey and medical examination in middle age (mean age 38.3 years) in 1985-1986 was used. Alcohol consu...... the potential confounding effect of alcohol use disorder, which is an established risk factor for mortality. This further highlights the importance of alcohol consumption measures in public health.......BACKGROUND: To examine the relationship of alcohol consumption, alcohol use disorder and mortality. METHOD: A cohort of 4316 male former Vietnam-era US army personnel participating in telephone survey and medical examination in middle age (mean age 38.3 years) in 1985-1986 was used. Alcohol...... consumption was reported in face-to-face interview on medical history and information on DSM-III alcohol use disorder was obtained from structured psychiatric interview (using the Diagnostic Interview Schedule). Mortality hazard during 15 years of follow-up was assessed with Cox proportional hazard regression...

  20. Alcohol abuse and related disorders treatment of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Yu. P. Sivolap

    2014-01-01

    Full Text Available Alcohol abuse and alcoholism are the leading causes of worse health and increased mortality rates. Excessive alcohol consumption is the third leading cause of the global burden of diseases and a leading factor for lower lifespan and higher mortality. Alcohol abuse decreases working capacity and efficiency and requires the increased cost of the treatment of alcohol-induced disorders, which entails serious economic losses. The unfavorable medical and social consequences of excessive alcohol use determine the importance of effective treatment for alcoholism. The goals of rational pharmacotherapy of alcohol dependence are to enhance GABA neurotransmission, to suppress glutamate neurotransmission, to act on serotonin neurotransmission, to correct water-electrolyte balance, and to compensate for thiamine deficiency. Alcoholism treatment consists of two steps: 1 the prevention and treatment of alcohol withdrawal syndrome and its complications (withdrawal convulsions and delirium alcoholicum; 2 antirecurrent (maintenance therapy. Benzodiazepines are the drugs of choice in alleviating alcohol withdrawal and preventing its convulsive attacks and delirium alcoholicum. Diazepam and chlordiazepoxide are most commonly used for this purpose; the safer drugs oxazepam and lorazepam are given to the elderly and patients with severe liver lesions. Anticonvulsants having normothymic properties, such as carbamazepine, valproic acid, topiramate, and lamotrigine, are a definite alternative to benzodiazepines. The traditional Russian clinical practice (clearance detoxification has not a scientific base or significant impact on alcohol withdrawal-related states in addicts. Relapse prevention and maintenance therapy for alcohol dependence are performed using disulfiram, acamprosate, and naltrexone; since 2013 the European Union member countries have been using, besides these agents, nalmefene that is being registered in Russia. Memantine and a number of other

  1. Fuel alcohol opportunities for Indiana

    Energy Technology Data Exchange (ETDEWEB)

    Greenglass, Bert

    1980-08-01

    Prepared at the request of US Senator Birch Bayh, Chairman of the National Alcohol Fuels Commission, this study may be best utilized as a guidebook and resource manual to foster the development of a statewide fuel alcohol plan. It examines sectors in Indiana which will impact or be impacted upon by the fuel alcohol industry. The study describes fuel alcohol technologies that could be pertinent to Indiana and also looks closely at how such a fuel alcohol industry may affect the economic and policy development of the State. Finally, the study presents options for Indiana, taking into account the national context of the developing fuel alcohol industry which, unlike many others, will be highly decentralized and more under the control of the lifeblood of our society - the agricultural community.

  2. Alcoholic cirrhosis and hepatocellular carcinoma.

    Science.gov (United States)

    Stickel, Felix

    2015-01-01

    Hepatocellular carcinoma shows a rising incidence worldwide, and the largest burden of disease in Western countries derives from patients with alcoholic liver disease (ALD) and cirrhosis, the latter being the premier premalignant factor for HCC. The present chapter addresses key issues including the epidemiology of alcohol-associated HCC, and its link to other coexisting non-alcoholic liver diseases, and additional host and environmental risk factors including the underlying genetics. Also discussed are molecular mechanisms of alcohol-associated liver cancer evolution involving the mediators of alcohol toxicity and carcinogenicity, acetaldehyde and reactive oxygen species, as well as the recently described mutagenic adducts which these mediators form with DNA. Specifically, interference of alcohol with retinoids and cofactors of transmethylation processes are outlined. Information presented in this chapter illustrates that the development of HCC in the context of ALD is multifaceted and suggests several molecular targets for prevention and markers for the screening of risk groups. PMID:25427904

  3. Construct validation of the scale of attitudes toward alcohol, alcoholism and individuals with alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Divane de Vargas

    2014-08-01

    Full Text Available Background : The attitudes toward issues related to alcohol and alcoholism have been noted as important predictors of the quantity and quality of care provided to individuals who have problems related to alcohol use. The Scale of Attitudes toward Alcohol, Alcoholism and Alcoholics (EAFAAA (Escala de Atitudes Frente ao Álcool, ao Alcoolismo e à pessoa com transtornos relacionados ao uso do álcool – EAFAAA has been widely used among students in health-related fields. However, the psychometric properties of this instrument have not been tested among professionals. Objective : The goal of this study was to determine the construct validity of the EAFAAA for use among health professionals. Methods : A preliminary version of the EAFAAA was distributed to a sample of health care professionals (n = 1,025. For the construct validation of the scale, the data were subjected to a factorial analysis, and the internal consistency was examined; the cutoff score of the instrument was determined using a receiver operating characteristic (ROC curve. Results : The exploratory factor analysis and the refinement of the EAFAAA items resulted in a final version consisting of 50 items divided into four factors: (1 Work and interpersonal relationships with patients with alcohol use disorders, (2 The individual with an alcohol use disorder, (3 Etiology of alcoholism and (4 Alcoholic beverages and their use. The internal consistency of the scale was considered adequate (Cronbach’s α > 0.80, and the instrument cutoff score was set at 3.15. Discussion : The results suggest that the instrument is valid for identifying attitudes towards alcohol, alcoholism and individuals with alcohol use disorders among health professionals.

  4. Alcohol Use and Abuse: Understanding Alcohol Use Across Your Lifespan | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Alcohol Use and Abuse Understanding Alcohol Use Across Your Lifespan Past Issues / Winter 2013 Table of Contents Alcohol use and the risk for alcohol-related problems ...

  5. Alcohol harm reduction in Europe.

    OpenAIRE

    Herring, Rachel; Thom, Betsy; Beccaria, Franca; Kolind, Torsten; Moskalewicz, Jacek

    2010-01-01

    This chapter provides an overview of harm reduction approaches to alcohol in Europe. First, definitions ascribed to alcohol harm reduction are outlined. Then, evaluated alcohol harm reduction interventions in European countries are described and the evidence for their effectiveness examined. These include multi-component programmes, improvements to the drinking environment, and initiatives to reduce the harms associated with drink-driving. Third, harm reduction activities that have been re...

  6. Decerebrate posturing in alcoholic coma.

    OpenAIRE

    Ireland, A J; Grant, P T

    1994-01-01

    Two cases of alcoholic coma are presented where extensor responses to noxious stimuli are demonstrated. Decerebrate posturing normally indicates severe structural or functional depression of midbrain function but can be caused by depressant drugs. Blood alcohol measurements are a vital test in the comatose patient as the clinical picture may be caused, or temporarily significantly worsened, by severe alcohol intoxication. The preservation of pupillary light reflexes in the presence of deep co...

  7. Suicidal Behavior and Alcohol Abuse

    OpenAIRE

    Maurizio Pompili; Gianluca Serafini; Marco Innamorati; Giovanni Dominici; Stefano Ferracuti; Kotzalidis, Giorgio D.; Giulia Serra; Paolo Girardi; Luigi Janiri; Roberto Tatarelli; Leo Sher; David Lester

    2010-01-01

    Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically...

  8. Alcohol and the Asian Glow

    OpenAIRE

    Young, Brian

    1999-01-01

    Facial flushing is a common hypersensitivity reaction that may be observed in many Asians following low to moderate alcohol consumption. Flushing can be accompanied by other symptoms such as tachycardia, nausea, and dizziness. Recent studies have shown that this flushing reaction is due to the presence of ALDH2*2, an inactive allele for the alcohol dehydrogenase gene found in approximately 50% of Asians. Aldehyde dehydrogenase (ALDH) is an important enzyme in alcohol metabolism, and deficienc...

  9. Alcohol Dependence, Withdrawal, and Relapse

    OpenAIRE

    Howard C Becker

    2008-01-01

    Continued excessive alcohol consumption can lead to the development of dependence that is associated with a withdrawal syndrome when alcohol consumption is ceased or substantially reduced. This syndrome comprises physical signs as well as psychological symptoms that contribute to distress and psychological discomfort. For some people the fear of withdrawal symptoms may help perpetuate alcohol abuse; moreover, the presence of withdrawal symptoms may contribute to relapse after periods of absti...

  10. 27 CFR 21.113 - Isopropyl alcohol.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Isopropyl alcohol. 21.113 Section 21.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants §...

  11. 27 CFR 21.116 - Methyl alcohol.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Methyl alcohol. 21.116 Section 21.116 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants §...

  12. 27 CFR 19.398 - Alcohol.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alcohol. 19.398 Section 19.398 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... Articles Bottling, Packaging, and Removal of Products § 19.398 Alcohol. (a) Containers. Subject to...

  13. Alcohol myopia and goal commitment

    Directory of Open Access Journals (Sweden)

    A. Timur Sevincer

    2014-03-01

    Full Text Available According to alcohol-myopia theory, acute alcohol consumption leads people to disproportionally focus on the salient rather than the peripheral aspects of a situation. We summarize various studies exploring how myopic processes resulting from acute alcohol intake affect goal commitment. After consuming alcohol student participants felt strongly committed to an important personal goal even though they had low expectations of successfully attaining the goal. However, once intoxicated participants were sober again (i.e., not myopic anymore they failed to act on their goal commitment. In line with alcohol-myopia theory, strong goal commitment as a result of alcohol intake was mediated by intoxicated (vs. sober participants disproportionally focusing on the desirability rather than the feasibility of their goal. Further supporting alcohol-myopia theory, when the low feasibility of attaining a particular goal was experimentally made salient (either explicitly or implicitly by subliminal priming, intoxicated participants felt less committed than those who consumed a placebo. We discuss these effects of acute alcohol intake in the context of research on the effects of chronic alcohol consumption on goal commitment.

  14. Alcohol, Athletic Performance and Recovery

    Directory of Open Access Journals (Sweden)

    David Cameron-Smith

    2010-07-01

    Full Text Available Alcohol consumption within elite sport has been continually reported both anecdotally within the media and quantitatively in the literature. The detrimental effects of alcohol on human physiology have been well documented, adversely influencing neural function, metabolism, cardiovascular physiology, thermoregulation and skeletal muscle myopathy. Remarkably, the downstream effects of alcohol consumption on exercise performance and recovery, has received less attention and as such is not well understood. The focus of this review is to identify the acute effects of alcohol on exercise performance and give a brief insight into explanatory factors.

  15. Deciding to quit drinking alcohol

    Science.gov (United States)

    ... Alcoholism - deciding to quit References American Psychiatric Association. Diagnostic and statistical manual of mental disorders . 5th ed. Arlington, VA: American Psychiatric Association, 2013. ...

  16. Selectively tritiated primary alcohols

    International Nuclear Information System (INIS)

    A procedure is suggested for the preparation of aliphatic primary alcohols selectively tritiated in the alpha position. The tritium donor is HTO; out of the catalysts tested, dichlorotris(triphenylphosphine)ruthenium(VI) gave the best results. The isotopic exchange can be performed over the temperature region of 130-200 degC. The amount of side products formed is negligible. The specific activity of the product is determined by the specific activity of HTO used and by the reactant ratio. The method is analogous to the reaction with D2O described by S.L. Regen in 1974. (author). 2 figs., 2 tabs., 17 refs

  17. The alcohol withdrawal syndrome.

    LENUS (Irish Health Repository)

    McKeon, A

    2008-08-01

    The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.

  18. Microstructure of neat alcohols

    CERN Document Server

    Perera, A; Zoranic, L; Perera, Aurelien; Sokolic, Franjo; Zoranic, Larisa

    2007-01-01

    Formation of microstructure in homogeneous associated liquids is analysed through the density-density pair correlation functions, both in direct and reciprocal space, as well as an effective local one-body density function. This is illustrated through a molecular dynamics study of two neat alcohols, namely methanol and \\emph{tert}-butanol, which have a rich microstructure: chain-like molecular association for the former and micelle-like for the latter. The relation to hydrogen bonding interaction is demonstrated. The apparent failure to find microstructure in water -a stronger hydrogen bonding liquid- with the same tools, is discussed.

  19. 77 FR 22795 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-04-17

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane,...

  20. 76 FR 49494 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-08-10

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... intramural programs and projects conducted by the NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM... Neuroimaging. Place: National Institutes of Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Terrance...

  1. 76 FR 69746 - National Institute On Alcohol Abuse And Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-11-09

    ... HUMAN SERVICES National Institutes of Health National Institute On Alcohol Abuse And Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... National Institutes Of Health, National Institute On Alcohol Abuse And Alcoholism, 5635 Fishers Lane,...

  2. 75 FR 69090 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-11-10

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism; Initial Review... Officer, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 5635...

  3. 76 FR 26311 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-05-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville, MD 20852,...

  4. 78 FR 35042 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-06-11

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... intramural programs and projects conducted by the National Institute on Alcohol Abuse and Alcoholism... Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 3061, Rockville, MD 20852, 301- 443-6076....

  5. 78 FR 55088 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-09-09

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... applications. Place: National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Bethesda, MD...

  6. 76 FR 15989 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-03-22

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis..., National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane,...

  7. 77 FR 43603 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-07-25

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Room 2081, Rockville,...

  8. 75 FR 10807 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-09

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis... Gunzerath, PhD, MBA, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism,...

  9. 76 FR 16798 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-03-25

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Room...

  10. 75 FR 10293 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-05

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Initial Review... Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Rm...

  11. 76 FR 26735 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-05-09

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., PhD, Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism, National...

  12. 75 FR 69091 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-11-10

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635...

  13. 75 FR 64733 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-20

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis... Review Branch, EPRB, National Institute on Alcohol Abuse and Alcoholism, National Institutes of...

  14. 78 FR 21616 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-11

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Foster, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism,...

  15. 77 FR 47654 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-08-09

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... intramural programs and projects conducted by the National Institute on Alcohol Abuse and Alcoholism..., National Institute of Health, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane,...

  16. 76 FR 17140 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-03-28

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635...

  17. 77 FR 33477 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Institutes of Health National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Rm 2017,...

  18. 77 FR 1706 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-01-11

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Buzas, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism,...

  19. 76 FR 44599 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-07-26

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review.... Foster, PhD, Scientific Review officer, National Institute on Alcohol Abuse & Alcoholism,...

  20. 76 FR 26308 - National Institute on Alcohol Abuse And Alcoholism; Notice of Meeting.

    Science.gov (United States)

    2011-05-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse And Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The.... Bautista, PhD, Executive Secretary, National Institute on Alcohol Abuse & Alcoholism National Institutes...

  1. 77 FR 39716 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-07-05

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis..., Alcohol Research Career Development Awards for Scientists and Clinicians; 93.272, Alcohol...

  2. 76 FR 39406 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2011-07-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The... Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, 5635 Fishers Lane, RM...

  3. 77 FR 52337 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meetings

    Science.gov (United States)

    2012-08-29

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Foster, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism,...

  4. 78 FR 25755 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-05-02

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville, MD 20852,...

  5. 76 FR 34719 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-06-14

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville, MD 20852,...

  6. 76 FR 59708 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-09-27

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis..., Alcohol Research ] Career Development Awards for Scientists and Clinicians; 93.272, Alcohol...

  7. 75 FR 42451 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-21

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Initial Review... Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Room...

  8. 77 FR 43604 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2012-07-25

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The... Alcohol Abuse & Alcoholism National Institutes of Health, 5635 Fishers Lane, Room 2085, Rockville,...

  9. 75 FR 43534 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-26

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism; Initial Review... Officer, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 5635...

  10. 75 FR 71711 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-11-24

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis..., EPRB, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635...

  11. 76 FR 2128 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-01-12

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review.... Srinivas, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism,...

  12. 75 FR 13293 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-19

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Initial Review... Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Rm. 2019, Bethesda, MD 20892. 301-443-2861....

  13. 77 FR 39713 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meetings

    Science.gov (United States)

    2012-07-05

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis....gov . Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis...

  14. 75 FR 53320 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-08-31

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis... Review Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,...

  15. 76 FR 59709 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-09-27

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville,...

  16. 76 FR 78015 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2011-12-15

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The... Alcohol Abuse & Alcoholism National Institutes of Health, 5635 Fishers Lane, Rm 2085, Rockville, MD...

  17. 77 FR 68135 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2012-11-15

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The... Alcohol Abuse & Alcoholism National Institutes of Health, 5635 Fishers Lane, Room 2085, Rockville,...

  18. 78 FR 41940 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-12

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Health, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, RM 2019, Bethesda,...

  19. 77 FR 22793 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-04-17

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, RM...

  20. 77 FR 64117 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-10-18

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... of personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special..., National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville, MD 20852,...

  1. 78 FR 75929 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-12-13

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... review and evaluate grant applications. Place: National Institute on Alcohol Abuse and Alcoholism,...

  2. 77 FR 2304 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-01-17

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism; Special Emphasis..., Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism,...

  3. 77 FR 43098 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-07-23

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis...., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room...

  4. 78 FR 73552 - National Institute On Alcohol Abuse and Alcoholism; National Institute On Drug Abuse; and...

    Science.gov (United States)

    2013-12-06

    ... HUMAN SERVICES National Institutes of Health National Institute On Alcohol Abuse and Alcoholism... meeting of the National Advisory Council on Alcohol Abuse and Alcoholism, National Advisory Council on... visit. Name of Committees: National Advisory Council on Alcohol Abuse and Alcoholism; National...

  5. 78 FR 20932 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2013-04-08

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The... Alcohol Abuse and Alcoholism. Date: June 12-13, 2013. Closed: June 12, 2013. Time: 5:00 p.m. to 7:30...

  6. 78 FR 45541 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2013-07-29

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The... Alcohol Abuse & Alcoholism, National Institutes of Health, 5635 Fishers Lane, Rm 2085, Rockville, MD...

  7. 76 FR 34718 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-06-14

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville, MD 20852,...

  8. 76 FR 44600 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-07-26

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, RM...

  9. 75 FR 42450 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-21

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review... Gunzerath, PhD, MBA, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism,...

  10. 75 FR 9421 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-02

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis..., National Institute on Alcohol Abuse & Alcoholism, 5635 Fishers Lane, Room 2085, Rockville, MD...

  11. 76 FR 50743 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-08-16

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville, MD 20852,...

  12. 75 FR 20852 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2010-04-21

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The...: Abraham P. Bautista, PhD, Executive Secretary, National Institute on Alcohol Abuse & Alcoholism,...

  13. 75 FR 46949 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2010-08-04

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... conducted by the National Institute on Alcohol Abuse and Alcoholism, including consideration of personnel... Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 3061, Rockville, MD 20852, 301-443-6076....

  14. 75 FR 10489 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-08

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Initial Review..., PhD, Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism, National...

  15. Do premorbid predictors of alcohol dependence also predict the failure to recover from alcoholism?

    DEFF Research Database (Denmark)

    Penick, Elizabeth C; Knop, Joachim; Nickel, Elizabeth J;

    2010-01-01

    In a search for viable endophenotypes of alcoholism, this longitudinal study attempted to identify premorbid predictors of alcohol dependence that also predicted the course of alcoholism.......In a search for viable endophenotypes of alcoholism, this longitudinal study attempted to identify premorbid predictors of alcohol dependence that also predicted the course of alcoholism....

  16. Should we train alcohol-dependent patients to avoid alcohol?

    NARCIS (Netherlands)

    R.W. Wiers; T.E. Gladwin; M. Rinck

    2013-01-01

    Spruyt et al. (2013) report an interesting study in which they compared an alcohol approach-bias, as measured with the Relevant-feature Stimulus Response Compatibility task (R-SRC) in 40 abstaining alcohol-dependent patients and 40 non-dependent controls. While controls had an approach-bias for alco

  17. NEUROBIOLOGICAL BASES OF ALCOHOL ADDICTION.

    Science.gov (United States)

    Matošić, Ana; Marušić, Srđan; Vidrih, Branka; Kovak-Mufić, Ana; Cicin-Šain, Lipa

    2016-03-01

    Alcohol addiction is a heterogeneous psychiatric disorder according to both phenotype and etiology. Difference in phenotype characteristics manifests in the manner the addiction arises, history of the alcoholic and history of drinking, comorbid disorders, and the phenomenon of abstinence difficulties. Concerning the etiology of alcoholism, the disease itself is considered to be a consequence of an interactive influence of the environment and genetic factors. Numerous researches conducted in the last decades discovered many aspects of the biochemical, cell and molecular bases of alcohol addiction, leading to a conclusion that alcoholism is, like many other addictions, a brain disease. By recognizing alcoholism as a disease which basically implies changes of the neurobiological mechanisms, as well as a clear genetic basis, it was supposed that the disease, having its basis solely in the symptomatology, is essentially heterogeneous. By trying to solve the problem of a clinically heterogeneous nature of the disease during the last fifty years, various sub-classifications of such patients have been suggested. According to Cloninger, subtypes of alcoholism differ also according to changes in the brain neurotransmission systems, i.e. it is supposed that patients suffering from alcoholism type 1 have a more pronounced dopaminergic transmission deficit, while dopaminergic transmission is not disturbed significantly in patients diagnosed with alcoholism type 2, who, however, have a significant lack of serotonergic transmission. In such a way, Cloninger actually presented the basis of the so-called neurobiological alcoholism model. Since he has connected differences in neurotransmission with differences in personality characteristics, this model is also known as the psychobiological model of alcoholism. The characteristic of alcoholism type 1 is avoiding damage (Harm Avoidance, HA) decreased dopamine transmission and increased serotonin transmission, while the significant

  18. NEUROBIOLOGICAL BASES OF ALCOHOL ADDICTION.

    Science.gov (United States)

    Matošić, Ana; Marušić, Srđan; Vidrih, Branka; Kovak-Mufić, Ana; Cicin-Šain, Lipa

    2016-03-01

    Alcohol addiction is a heterogeneous psychiatric disorder according to both phenotype and etiology. Difference in phenotype characteristics manifests in the manner the addiction arises, history of the alcoholic and history of drinking, comorbid disorders, and the phenomenon of abstinence difficulties. Concerning the etiology of alcoholism, the disease itself is considered to be a consequence of an interactive influence of the environment and genetic factors. Numerous researches conducted in the last decades discovered many aspects of the biochemical, cell and molecular bases of alcohol addiction, leading to a conclusion that alcoholism is, like many other addictions, a brain disease. By recognizing alcoholism as a disease which basically implies changes of the neurobiological mechanisms, as well as a clear genetic basis, it was supposed that the disease, having its basis solely in the symptomatology, is essentially heterogeneous. By trying to solve the problem of a clinically heterogeneous nature of the disease during the last fifty years, various sub-classifications of such patients have been suggested. According to Cloninger, subtypes of alcoholism differ also according to changes in the brain neurotransmission systems, i.e. it is supposed that patients suffering from alcoholism type 1 have a more pronounced dopaminergic transmission deficit, while dopaminergic transmission is not disturbed significantly in patients diagnosed with alcoholism type 2, who, however, have a significant lack of serotonergic transmission. In such a way, Cloninger actually presented the basis of the so-called neurobiological alcoholism model. Since he has connected differences in neurotransmission with differences in personality characteristics, this model is also known as the psychobiological model of alcoholism. The characteristic of alcoholism type 1 is avoiding damage (Harm Avoidance, HA) decreased dopamine transmission and increased serotonin transmission, while the significant

  19. Parental Alcohol Involvement and Adolescent Alcohol Expectancies Predict Alcohol Involvement in Male Adolescents

    OpenAIRE

    Cranford, James A.; Zucker, Robert A.; Jester, Jennifer M.; Puttler, Leon I.; Fitzgerald, Hiram E.

    2010-01-01

    Current models of adolescent drinking behavior hypothesize that alcohol expectancies mediate the effects of other proximal and distal risk factors. This longitudinal study tested the hypothesis that the effects of parental alcohol involvement on their children’s drinking behavior in mid-adolescence are mediated by the children’s alcohol expectancies in early adolescence. A sample of 148 initially 9–11 year old boys and their parents from a high-risk population and a contrast group of communit...

  20. Physician's information about alcohol problems at hospitalisation of alcohol misusers

    DEFF Research Database (Denmark)

    Nielsen, S D; Gluud, C

    1992-01-01

    Information was gathered on recognition and treatment of alcohol problems in the primary and secondary health sectors, the latter represented by a department of hepatology. The general practitioner finds in most cases (18/26, 69%) that it is relevant to advise about a patient's alcohol misuse...... significantly less often in female compared to male patients (75% vs. 94%; P alcohol misusers were under treatment with thiamine/B-vitamins and/or disulfiram before admission. There was a significant difference (P ... practitioner wrote alcohol misuse on the admission form and when he did not (37% vs. 10%). At admission, treatment was begun in 54%, and by the discharge 78% were under treatment. Further quality assurance in the diagnosis and treatment of patients with alcohol problems is needed....

  1. Microbial alcohol dehydrogenases: identification, characterization and engineering

    NARCIS (Netherlands)

    Machielsen, M.P.

    2007-01-01

    Keywords: alcohol dehydrogenase, laboratory evolution, rational protein engineering, Pyrococcus furiosus, biocatalysis, characterization, computational design, thermostability.   Alcohol dehydrogeases (ADHs) catalyze the interconversion of alcohols, aldehydes and ketones. They display a wide variety

  2. [Influence of alcohol beverage vending machine on alcohol dependence syndrome].

    Science.gov (United States)

    Ino, A; Fujita, S

    1994-12-01

    The vending machines which sell alcohol beverages (AVM) can be found quite easily in front of shops or on the roadside in this country. Although it is easily supposed that these vending machines might have badly influenced on developing alcohol dependence syndrome, no scientific study has been reported in this regard so far. In this study, we analyzed the present status of alcoholics (n = 759) and their family members (n = 512) and of ordinary people (n = 334) in terms of their "relation" and "attitudes" to the vending machines by a questionnaire method. The results obtained show as follows: The majority of alcoholics (60%) had used AVM a couple of times or more often in a week, and 18% of alcoholics had not used AVM at all. It was found that the natures of AVM such as "machine," "long time operation," "easy accessibility," are closely related to the development of their alcohol seeking behavior, resulting in forming unfavorable drinking patterns such as concealed drinking, gulping, early morning drinking or binge drinking. Unusual patterns of using AVM were also noticed among them, such as, go to AVM before 5 a.m. and wait until it starts to work, go to a far away AVM deliberately, or, visiting AVM one after another. It was noticed that these drinking habits affected seriously not only the alcoholics but their families also. The number of the family members who insisted that AVM affected badly on the course of alcohol dependence syndrome is larger than that of alcoholics who admit the same thing. As for the future abolition of AVM, 91% of the family members, 70% of alcoholics and 39% of ordinary persons agreed with. The rate of "agreed with abolition" is higher than that of "disagreed with abolition" among ordinary persons. PMID:7695515

  3. [Adolescence and alcohol].

    Science.gov (United States)

    Giorgi, Pier Luigi

    2005-01-01

    Anna Freud defined adolescence "evolutional disorder", meaning also a compulsory and temporary shift. Corresponding, biologically, to the puberty, it is an age full of expectations and hopes, nevertheless not free from psychological and social risks: because of a changing relation with family, of the searching of new models, of the coming in contact with less protective contexts, of the differentiation of affective expectations. Therefore it can be that the passing from childhood to active subjectivity brings on anxiety, conflicts and deviance; and it can suggest illusory remedies as overindulgence in alcohol, alarming phenomenon denounced by WHO and by many other international and Italian institutions. After these preliminary remarks, the A. reminds as alcohol and its by-products reached Europe, describes its metabolism and its biological effects, the genetic factors which could predispose to the tolerance and/or to the addiction, the environmental and social ones, and the costs, both individual and public. Conclusions want suggest two omens: the reclamation of a new kind of family relation, based on listening and dialogue; and the achievement of a concrete alliance between society and young adult, which could conjugate the expectations of the community with the rights of the new subject for a free and integrated growing up. PMID:16209112

  4. Neural mechanisms of pain and alcohol dependence☆

    OpenAIRE

    Apkarian, A. Vania; Neugebauer, Volker; Koob, George; Edwards, Scott; Levine, Jon D.; Ferrari, Luiz; Egli, Mark; Regunathan, Soundar

    2013-01-01

    An association between chronic pain conditions and alcohol dependence has been revealed in numerous studies with episodes of alcohol abuse antedating chronic pain in some people and alcohol dependence emerging after the onset of chronic pain in others. Alcohol dependence and chronic pain share common neural circuits giving rise to the possibility that chronic pain states could significantly affect alcohol use patterns and that alcohol dependence could influence pain sensitivity. The reward an...

  5. Elderly alcoholics in outpatient treatment

    DEFF Research Database (Denmark)

    Nielsen, Bent; Nielsen, Anette Søgaard; Lolk, Anette;

    2010-01-01

    In Denmark, the treatment of alcoholics is provided by public outpatient alcohol clinics. The purpose of this study was to investigate whether elderly patients differ from younger patients with regards to sociodemographic data, drinking pattern and psychiatric comorbidity which may affect...

  6. Alcohol and Women. Pamphlet Series.

    Science.gov (United States)

    Gomberg, Edith S. Lisansky

    Reasonable and moderate drinking is considered acceptable by the major portion of the population. Although women consume less alcohol than men, alcohol has a greater intoxicating effect for women than for men because of the differences in body water content and proportion of fatty tissue. The prevalence rate of drinking is virtually identical for…

  7. The alcohol patient and surgery

    DEFF Research Database (Denmark)

    Tønnesen, H

    1999-01-01

    Alcohol abusers have a threefold increased risk of post-operative morbidity after surgery. The most frequent complications are infections, cardiopulmonary insufficiency, and bleeding episodes. Pathogenesis is suppressed immune capacity, subclinical cardiac dysfunction, and haemostatic imbalance....... The economic implications of alcohol abuse in surgical patients are tremendous. Interventional studies are required to reduce future increases in post-operative morbidity....

  8. The concept of alcohol craving.

    Directory of Open Access Journals (Sweden)

    Katarzyna Agnieszka Iwanicka

    2015-04-01

    Full Text Available The aim of the article was to assess how the perception of alcohol craving, which is one of the symptoms of alcohol dependence, evolved, as well as how it was reflected in the diagnostic classifications. The purpose of this article was also a discussion of the models of the origins of craving, explaining the etiology of this phenomenon and the tools for measuring this concept. The concept of craving, defined as a strong need or compulsion to drink alcohol, functioned for many years, not only in the clinical practice but also as a concept inherently associated with alcohol dependence. However, among experts and researchers, there was no consensus about the etiology of this phenomenon and its development. Some emphasize the emotional – motivational aspect of it, while in the literature also its cognitive – behavioral nature is highlighted. Craving as a symptom has been recognized as a diagnostic criterion of alcohol dependence in the International Statistical Classification of Diseases and Related Health Problems – ICD 10. In the year 2013, it was also indicated as a symptom of disorder resulting from alcohol abuse in the Diagnostic and Statistical Manual of Mental Disorders – DSM 5. It seems to be significant also to discuss the tools used to measure craving, both in clinical trials and therapeutic practice, among them: the Alcohol Specific Role Play Test, Obsessive Compulsive Drinking Scale (OCDS Lubeck Craving Scale (LCRR and Alcohol Urge Questionnaire (AUQ.

  9. [The concept of alcohol craving].

    Science.gov (United States)

    Iwanicka, Katarzyna Agnieszka; Olajossy, Marcin

    2015-01-01

    The aim of the article was to assess how the perception of alcohol craving, which is one of the symptoms of alcohol dependence, evolved, as well as how it was reflected in the diagnostic classifications. The purpose of this article was also a discussion of the models of the origins of craving, explaining the etiology of this phenomenon and the tools for measuring this concept. The concept of craving, defined as a strong need or compulsion to drink alcohol, functioned for many years, not only in the clinical practice but also as a concept inherently associated with alcohol dependence. However, among experts and researchers, there was no consensus about the etiology of this phenomenon and its development. Some emphasize the emotional - motivational aspect of it, while in the literature also its cognitive - behavioral nature is highlighted. Craving as a symptom has been recognized as a diagnostic criterion of alcohol dependence in the International Statistical Classification of Diseases and Related Health Problems - ICD 10. In the year 2013, it was also indicated as a symptom of disorder resulting from alcohol abuse in the Diagnostic and Statistical Manual of Mental Disorders - DSM 5. It seems to be significant also to discuss the tools used to measure craving, both in clinical trials and therapeutic practice, among them: the Alcohol Specific Role Play Test, Obsessive Compulsive Drinking Scale (OCDS) Lubeck Craving Scale (LCRR) and Alcohol Urge Questionnaire (AUQ).

  10. Job strain and alcohol intake

    DEFF Research Database (Denmark)

    Heikkilä, Katriina; Nyberg, Solja T; Fransson, Eleonor I;

    2012-01-01

    The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job...... strain) and alcohol intake....

  11. From alcohol toxicity to treatment

    NARCIS (Netherlands)

    Seitz, HK; Salaspuro, M; Savolainen, M; Haber, P; Ishii, H; Teschke, R; Moshage, H; Lieber, CS

    2005-01-01

    This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism in Mannheim, Germany, in October 2004. This symposium was dedicated to Charles S. Lieber in recognition of his contribution in alcohol research over the last 50

  12. The alcohol fuels in Guatemala

    International Nuclear Information System (INIS)

    This presentation shows the antecedents of the production of alcohol fuel in Guatemala as an alternative to imported gasoline, also presents current statistics of consumption, importation of liquid fossil fuels, production of alcohol fuel, consumption, and trends of consumption mixed with gasoline and yield data

  13. Alcohol: taking a population perspective.

    Science.gov (United States)

    Gilmore, William; Chikritzhs, Tanya; Stockwell, Tim; Jernigan, David; Naimi, Timothy; Gilmore, Ian

    2016-07-01

    Alcohol consumption is a global phenomenon, as is the resultant health, social and economic harm. The nature of these harms varies with different drinking patterns and with the societal and political responses to the burden of harm; nevertheless, alcohol-related chronic diseases have a major effect on health. Strong evidence exists for the effectiveness of different strategies to minimize this damage and those policies that target price, availability and marketing of alcohol come out best, whereas those using education and information are much less effective. However, these policies can be portrayed as anti-libertarian and so viewing them in the context of alcohol-related harm to those other than the drinker, such as the most vulnerable in society, is important. When this strategy is successful, as in Scotland, it has been possible to pass strong and effective legislation, such as for a minimum unit price for alcohol. PMID:27188823

  14. Breast-feeding and alcoholism

    DEFF Research Database (Denmark)

    Goodwin, D W; Gabrielli, W F; Penick, E C;

    1999-01-01

    OBJECTIVE: The authors' goal was to determine whether early termination of breast-feeding contributes to later alcohol dependence, as proposed more than 200 years ago by the British physician Thomas Trotter. METHOD: In 1959-1961, a multiple-specialty group of physicians studied 9, 182 consecutive...... diagnosed as alcohol dependent at age 30, 13 (48%) came from the group weaned from the breast before the age of 3 weeks; only 33 (19%) of the 173 non-alcohol-dependent subjects came from the early weaning group. When challenged by other perinatal variables in a multiple regression analysis, early weaning...... significantly contributed to the prediction of the severity of alcoholism at age 30. CONCLUSIONS: The data support the hypothesis that early weaning may be associated with a greater risk of alcohol dependence later in life....

  15. Alcohol abuse and postoperative morbidity

    DEFF Research Database (Denmark)

    Tønnesen, Hanne

    2003-01-01

    Patients who drink too much have more complications after surgery. The aim of this thesis was to evaluate the evidence, possible mechanisms, and prevention of the increased postoperative morbidity in alcohol abusers, defined by a consumption of at least five drinks per day. The literature could...... be criticised for several methodological flaws. Nevertheless, the results are in agreement showing moderate to strong evidence of increased postoperative morbidity after surgical procedures on alcohol abusers. There is weak to moderate evidence of increased postoperative mortality, hospital stay, and re......-operation. The personal and economic consequences are tremendous. The incidence of alcohol abusers undergoing surgery was 7% to 49%, according to gender and diagnosis. They have been identified by a self-reported alcohol intake, which implies the possibility of underestimation. Alcohol markers could be used for a more...

  16. Alcohol reduces aversion to ambiguity

    Directory of Open Access Journals (Sweden)

    Tadeusz eTyszka

    2015-01-01

    Full Text Available Several years ago, Cohen, Dearnaley, and Hansel [1] demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly [2]. The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar, where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women.

  17. Alcohol dependency prevention and early intervention.

    OpenAIRE

    Nathan, P E

    1988-01-01

    Current data on efforts to prevent alcoholism indicate that we are better able to prevent some of the consequences of alcohol misuse, such as alcohol-related car crashes and fetal alcohol syndrome, than chronic alcohol dependence itself. A review of data on outcomes of treatment for long-term alcohol dependence indicates that 9 of 10 alcohol dependent persons receive no treatment for the disorder in any given year. When treatment is provided for long-term alcohol dependent persons, it has onl...

  18. Individual susceptibility to alcoholic pancreatitis.

    Science.gov (United States)

    Apte, Minoti V; Pirola, Romano C; Wilson, Jeremy S

    2008-03-01

    The observation that only a minority of heavy drinkers develop pancreatitis has prompted an intensive search for a trigger factor/cofactor/susceptibility factor that may precipitate a clinical attack. Putative susceptibility factors examined so far include diet, smoking, amount and type of alcohol consumed, the pattern of drinking and lipid intolerance. In addition, a range of inherited factors have been assessed including blood group antigens, human leukocyte antigen serotypes, alpha-1-antitrypsin phenotypes and several genotypes. The latter group comprises mutations/polymorphisms in genes related to alcohol-metabolizing enzymes, detoxifying enzymes, pancreatic digestive enzymes, pancreatic enzyme inhibitors, cystic fibrosis and cytokines. Disappointingly, despite this concerted research effort, no clear association has been established between the above factors and alcoholic pancreatitis. Experimentally, the secretagogue cholecystokinin (CCK) has been investigated as a candidate 'trigger' for alcoholic pancreatitis. However, the clinical relevance of CCK as a trigger factor has to be questioned, as it is difficult to envisage a situation in humans where abnormally high levels of CCK would be released into the circulation to trigger pancreatitis in alcoholics. In contrast, bacterial endotoxemia is a candidate cofactor that does have relevance to the clinical situation. Plasma lipopolysaccharide (LPS, an endotoxin) levels are significantly higher in drinkers (either after chronic alcohol intake or a single binge) compared to non-drinkers. We have recently shown that alcohol-fed animals challenged with otherwise innocuous doses of LPS exhibit significant pancreatic injury. Moreover, repeated LPS exposure in alcohol-fed rats leads to progressive injury to the gland characterized by significant pancreatic fibrosis. These studies support the concept that endotoxin may be an important factor in the initiation and progression of alcoholic pancreatitis. Scope remains for

  19. Alcohol ignition interlock programs.

    Science.gov (United States)

    Beirness, D J; Marques, P R

    2004-09-01

    The alcohol ignition interlock is an in-vehicle DWI control device that prevents a car from starting until the operator provides a breath alcohol concentration (BAC) test below a set level, usually .02% (20 mg/dl) to .04% (40 mg/dl). The first interlock program was begun as a pilot test in California 18 years ago; today all but a few US states, and Canadian provinces have interlock enabling legislation. Sweden has recently implemented a nationwide interlock program. Other nations of the European Union and as well as several Australian states are testing it on a small scale or through pilot research. This article describes the interlock device and reviews the development and current status of interlock programs including their public safety benefit and the public practice impediments to more widespread adoption of these DWI control devices. Included in this review are (1) a discussion of the technological breakthroughs and certification standards that gave rise to the design features of equipment that is in widespread use today; (2) a commentary on the growing level of adoption of interlocks by governments despite the judicial and legislative practices that prevent more widespread use of them; (3) a brief overview of the extant literature documenting a high degree of interlock efficacy while installed, and the rapid loss of their preventative effect on repeat DWI once they are removed from the vehicles; (4) a discussion of the representativeness of subjects in the current research studies; (5) a discussion of research innovations, including motivational intervention efforts that may extend the controlling effect of the interlock, and data mining research that has uncovered ways to use the stored interlock data record of BAC tests in order to predict high risk drivers; and (6) a discussion of communication barriers and conceptual rigidities that may be preventing the alcohol ignition interlock from taking a more prominent role in the arsenal of tools used to control

  20. Eyeblink Classical Conditioning in Alcoholism and Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Cheng, Dominic T; Jacobson, Sandra W; Jacobson, Joseph L; Molteno, Christopher D; Stanton, Mark E; Desmond, John E

    2015-01-01

    Alcoholism is a debilitating disorder that can take a significant toll on health and professional and personal relationships. Excessive alcohol consumption can have a serious impact on both drinkers and developing fetuses, leading to long-term learning impairments. Decades of research in laboratory animals and humans have demonstrated the value of eyeblink classical conditioning (EBC) as a well-characterized model system to study the neural mechanisms underlying associative learning. Behavioral EBC studies in adults with alcohol use disorders and in children with fetal alcohol spectrum disorders report a clear learning deficit in these two patient populations, suggesting alcohol-related damage to the cerebellum and associated structures. Insight into the neural mechanisms underlying these learning impairments has largely stemmed from laboratory animal studies. In this mini-review, we present and discuss exemplary animal findings and data from patient and neuroimaging studies. An improved understanding of the neural mechanisms underlying learning deficits in EBC related to alcoholism and prenatal alcohol exposure has the potential to advance the diagnoses, treatment, and prevention of these and other pediatric and adult disorders.

  1. Access to alcohol outlets, alcohol consumption and mental health.

    Directory of Open Access Journals (Sweden)

    Gavin Pereira

    Full Text Available The objective of this study was to investigate residential exposure to alcohol outlets in relation to alcohol consumption and mental health morbidity (anxiety, stress, and depression. This was a cross-sectional study of 6,837 adults obtained from a population representative sample for the period 2006-2009 in Perth, Western Australia. The number of alcohol outlets was ascertained for a 1600 m service area surrounding the residential address. Zero-inflated negative binomial and logistic regression were used to assess associations with total alcohol consumption, harmful alcohol consumption (7-10 drinks containing 10 g of alcohol for men, 5-6 drinks for women and medically diagnosed and hospital contacts (for anxiety, stress, and depression, respectively. The rate ratio for the number of days of harmful consumption of alcohol per month and the number of standard drinks of alcohol consumed per drinking day was 1.06 (95% CI: 1.02, 1.11 and 1.01 (95% CI: 1.00, 1.03 for each additional liquor store within a 1600 m service area, respectively. The odds ratio of hospital contact for anxiety, stress, or depression was 1.56 (95% CI: 0.98, 2.49 for those with a liquor store within the service area compared to those without. We observed strong evidence for a small association between residential exposure to liquor stores and harmful consumption of alcohol, and some support for a moderate-sized effect on hospital contacts for anxiety, stress, and depression.

  2. Parental alcohol use, alcohol-related problems, and alcohol-specific attitudes, alcohol-specific communication, and adolescent excessive alcohol use and alcohol-related problems: An indirect path model

    NARCIS (Netherlands)

    Mares, S.H.W.; Vorst, H. van der; Engels, R.C.M.E.; Lichtwarck-Aschoff, A.

    2011-01-01

    Alcohol-specific parent-child communication has often been studied in relation to regular alcohol use of adolescents. However, it might be as important to focus on adolescent problematic alcohol use. In addition, the way parents communicate with their children about alcohol might depend on their own

  3. A novel aldose-aldose oxidoreductase for co-production of D-xylonate and xylitol from D-xylose with Saccharomyces cerevisiae.

    Science.gov (United States)

    Wiebe, Marilyn G; Nygård, Yvonne; Oja, Merja; Andberg, Martina; Ruohonen, Laura; Koivula, Anu; Penttilä, Merja; Toivari, Mervi

    2015-11-01

    An open reading frame CC1225 from the Caulobacter crescentus CB15 genome sequence belongs to the Gfo/Idh/MocA protein family and has 47 % amino acid sequence identity with the glucose-fructose oxidoreductase from Zymomonas mobilis (Zm GFOR). We expressed the ORF CC1225 in the yeast Saccharomyces cerevisiae and used a yeast strain expressing the gene coding for Zm GFOR as a reference. Cell extracts of strains overexpressing CC1225 (renamed as Cc aaor) showed some Zm GFOR type of activity, producing D-gluconate and D-sorbitol when a mixture of D-glucose and D-fructose was used as substrate. However, the activity in Cc aaor expressing strain was >100-fold lower compared to strains expressing Zm gfor. Interestingly, C. crescentus AAOR was clearly more efficient than the Zm GFOR in converting in vitro a single sugar substrate D-xylose (10 mM) to xylitol without an added cofactor, whereas this type of activity was very low with Zm GFOR. Furthermore, when cultured in the presence of D-xylose, the S. cerevisiae strain expressing Cc aaor produced nearly equal concentrations of D-xylonate and xylitol (12.5 g D-xylonate l(-1) and 11.5 g D-xylitol l(-1) from 26 g D-xylose l(-1)), whereas the control strain and strain expressing Zm gfor produced only D-xylitol (5 g l(-1)). Deletion of the gene encoding the major aldose reductase, Gre3p, did not affect xylitol production in the strain expressing Cc aaor, but decreased xylitol production in the strain expressing Zm gfor. In addition, expression of Cc aaor together with the D-xylonolactone lactonase encoding the gene xylC from C. crescentus slightly increased the final concentration and initial volumetric production rate of both D-xylonate and D-xylitol. These results suggest that C. crescentus AAOR is a novel type of oxidoreductase able to convert the single aldose substrate D-xylose to both its oxidized and reduced product.

  4. A novel aldose-aldose oxidoreductase for co-production of D-xylonate and xylitol from D-xylose with Saccharomyces cerevisiae.

    Science.gov (United States)

    Wiebe, Marilyn G; Nygård, Yvonne; Oja, Merja; Andberg, Martina; Ruohonen, Laura; Koivula, Anu; Penttilä, Merja; Toivari, Mervi

    2015-11-01

    An open reading frame CC1225 from the Caulobacter crescentus CB15 genome sequence belongs to the Gfo/Idh/MocA protein family and has 47 % amino acid sequence identity with the glucose-fructose oxidoreductase from Zymomonas mobilis (Zm GFOR). We expressed the ORF CC1225 in the yeast Saccharomyces cerevisiae and used a yeast strain expressing the gene coding for Zm GFOR as a reference. Cell extracts of strains overexpressing CC1225 (renamed as Cc aaor) showed some Zm GFOR type of activity, producing D-gluconate and D-sorbitol when a mixture of D-glucose and D-fructose was used as substrate. However, the activity in Cc aaor expressing strain was >100-fold lower compared to strains expressing Zm gfor. Interestingly, C. crescentus AAOR was clearly more efficient than the Zm GFOR in converting in vitro a single sugar substrate D-xylose (10 mM) to xylitol without an added cofactor, whereas this type of activity was very low with Zm GFOR. Furthermore, when cultured in the presence of D-xylose, the S. cerevisiae strain expressing Cc aaor produced nearly equal concentrations of D-xylonate and xylitol (12.5 g D-xylonate l(-1) and 11.5 g D-xylitol l(-1) from 26 g D-xylose l(-1)), whereas the control strain and strain expressing Zm gfor produced only D-xylitol (5 g l(-1)). Deletion of the gene encoding the major aldose reductase, Gre3p, did not affect xylitol production in the strain expressing Cc aaor, but decreased xylitol production in the strain expressing Zm gfor. In addition, expression of Cc aaor together with the D-xylonolactone lactonase encoding the gene xylC from C. crescentus slightly increased the final concentration and initial volumetric production rate of both D-xylonate and D-xylitol. These results suggest that C. crescentus AAOR is a novel type of oxidoreductase able to convert the single aldose substrate D-xylose to both its oxidized and reduced product. PMID:26264136

  5. An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo

    Science.gov (United States)

    Gayam, Srivardhan Reddy; Venkatesan, Parthiban; Sung, Yi-Ming; Sung, Shuo-Yuan; Hu, Shang-Hsiu; Hsu, Hsin-Yun; Wu, Shu-Pao

    2016-06-01

    The synthesis and characterization of an NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload ``cargo'' molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.The synthesis and characterization of an NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload ``cargo'' molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this

  6. Degradation of fluorotelomer alcohols

    DEFF Research Database (Denmark)

    Ellis, David A; Martin, Jonathan W; De Silva, Amila O;

    2004-01-01

    Human and animal tissues collected in urban and remote global locations contain persistent and bioaccumulative perfluorinated carboxylic acids (PFCAs). The source of PFCAs was previously unknown. Here we present smog chamber studies that indicate fluorotelomer alcohols (FTOHs) can degrade....... The significance of the gas-phase peroxy radical cross reactions that produce PFCAs has not been recognized previously. Such reactions are expected to occur during the atmospheric degradation of all polyfluorinated materials, necessitating a reexamination of the environmental fate and impact of this important...... in the atmosphere to yield a homologous series of PFCAs. Atmospheric degradation of FTOHs is likely to contribute to the widespread dissemination of PFCAs. After their bioaccumulation potential is accounted for, the pattern of PFCAs yielded from FTOHs could account for the distinct contamination profile of PFCAs...

  7. Mutagenicity of alcoholic beverages.

    Science.gov (United States)

    Nagao, M; Takahashi, Y; Wakabayashi, K; Sugimura, T

    1981-02-01

    The mutagenicities of evaporated residues of alcoholic beverages were tested by the Ames method with the modification of pre-incubation, by using Salmonella typhimurium TA100 and TA98. 12 of 13 brands of whisky were mutagenic to TA100 without S9 mix. Addition of S9 mix decreased or abolished these mutagenicities. 5 brands of brandy and 1 apple brandy were tested, and all showed a similar type of mutagenicity to that of whisky. A fraction of brand-K whisky, containing a major mutagen(s), eluted from XAD-2 column with water, gave 3800 revertants of TA100 per plate at a dose equivalent to 10 ml of whisky. PMID:7012607

  8. Alcohol y otras drogas

    OpenAIRE

    Juan Carlos González Sánchez

    2006-01-01

    En el siguiente artículo hacemos un breve recorrido por la polidependencia que actualmente genera más demanda en la red asistencial específica, hablamos del abuso/dependencia al binomio Alcohol-Cocaína. Realizamos un análisis del mecanismo de acción de su principal metabolito el Cocaetileno y su tratamiento actual. También hacemos un análisis del nivel relacional de estas drogas, y reseñamos la asignación terapéutica como orientación al abordaje bio-psico-social.ción de la adicción al juego....

  9. The alcohol program

    International Nuclear Information System (INIS)

    The rationale for the launching of the Alcohol Program from sugarcane in Brazil in the mid-1970s is described as an answer to the first ''oil crisis'' as well as a solution to the problem of the fluctuating sugar prices in the international market. The technical characteristics of ethanol as a fuel are given as well as a discussion of the evolution of the cost of production, environmental and social consequences. Regarding costs, ethanol production was close to 100 dollars a barrel in the initial stages of the Program in 1980 falling rapidly due to economies of scale and technological progress to half that value in 1990, followed by a slower decline in recent years. Considering the hard currency saved by avoiding oil importation through the significant displacement of gasoline by ethanol and the decrease in the amount of external debt that the displaced oil importation was able to provide it is possible to demonstrate that the Alcohol Program has been an efficient way of exchanging dollar debt by national currency subsidies which are paid by the liquid fossil fuel users. Even with this economic gains for society, the continuity of the Program is difficult to maintain. Two solutions to this problem are discussed: internal expansion of the use of ethanol and exports to industrialized countries where it could be used as an octane enhancer. The main attractiveness of the Program - the reduction of CO2 emissions as compared to fossil fuels - is stressed, mainly as a solution for industrialized countries to fulfill their commitments with the United Nations Framework Climate Change Convention. (Author)

  10. Alcohol references on undergraduate males' Facebook profiles.

    Science.gov (United States)

    Egan, Katie G; Moreno, Megan A

    2011-09-01

    Perceived peer alcohol use is a predictor of consumption in college males; frequent references to alcohol on Facebook may encourage alcohol consumption. Content analysis of college males' Facebook profiles identified references to alcohol. The average age of 225 identified profiles was 19.9 years. Alcohol references were present on 85.3% of the profiles; the prevalence of alcohol was similar across each undergraduate grade. The average number of alcohol references per profile was 8.5 but increased with undergraduate year (p = .003; confidence interval = 1.5, 7.5). Students who were of legal drinking age referenced alcohol 4.5 times more than underage students, and an increase in number of Facebook friends was associated with an increase in displayed alcohol references (p Facebook is widely used in the college population; widespread alcohol displays on Facebook may influence social norms and cause increases in male college students' alcohol use.

  11. Alcohol references on undergraduate males' Facebook profiles.

    Science.gov (United States)

    Egan, Katie G; Moreno, Megan A

    2011-09-01

    Perceived peer alcohol use is a predictor of consumption in college males; frequent references to alcohol on Facebook may encourage alcohol consumption. Content analysis of college males' Facebook profiles identified references to alcohol. The average age of 225 identified profiles was 19.9 years. Alcohol references were present on 85.3% of the profiles; the prevalence of alcohol was similar across each undergraduate grade. The average number of alcohol references per profile was 8.5 but increased with undergraduate year (p = .003; confidence interval = 1.5, 7.5). Students who were of legal drinking age referenced alcohol 4.5 times more than underage students, and an increase in number of Facebook friends was associated with an increase in displayed alcohol references (p Facebook is widely used in the college population; widespread alcohol displays on Facebook may influence social norms and cause increases in male college students' alcohol use. PMID:21406490

  12. Differences of Photographs Inducing Craving Between Alcoholics and Non-alcoholics

    OpenAIRE

    Lee, Eun; Namkoong, Kee; Lee, Choong Heon; An, Suk Kyoon; Lee, Byung Ook

    2006-01-01

    Many researchers have used cue reactivity paradigm to study alcohol craving. But the difference of craving response to drinks between alcoholic patients and social drinkers was little evaluated. To investigate characteristics of alcohol-related visual cues which induce alcohol craving in alcoholism, we examined the response of subjects to alcohol-related cues considering qualitative aspects. The authors developed 27 photographs related to alcohol as candidate visual cues. Thirty five patients...

  13. The cognitive and behavioural impact of alcohol promoting and alcohol warning advertisements: An experimental study

    OpenAIRE

    Brown, Kyle; Stautz, Kaidy; Hollands, Gareth; Winpenny, Eleanor; Marteau, Theresa

    2015-01-01

    Aims: To assess the immediate effect of alcohol promoting and alcohol warning advertisements on implicit and explicit attitudes towards alcohol and on alcohol seeking behaviour. Methods: We conducted a between-participants online experiment in which participants were randomly assigned to view one of three sets of advertisements: i. alcohol promoting, ii. alcohol warning, or iii. unrelated to alcohol. A total of 373 participants (59.5% female) aged 18 to 40 (M = 28.03) living in t...

  14. Effects of alcohol intake on brain structure and function in non-alcohol-dependent drinkers

    OpenAIRE

    Bruin, Eveline Astrid de

    2005-01-01

    About 85% of the adult population in the Netherlands regularly drinks alcohol. Chronic excessive alcohol intake in alcohol-dependent individuals is known to have damaging effects on brain structure and function. Relatives of alcohol-dependent individuals display differences in brain function that are similar to those found in alcoholics, even if they have never been drinking alcohol. This suggests that brain damage in alcohol-dependent individuals is at least partly related to genetic factors...

  15. Alcohol fuels program technical review

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-07-01

    The last issue of the Alcohol Fuels Process R/D Newsletter contained a work breakdown structure (WBS) of the SERI Alcohol Fuels Program that stressed the subcontracted portion of the program and discussed the SERI biotechnology in-house program. This issue shows the WBS for the in-house programs and contains highlights for the remaining in-house tasks, that is, methanol production research, alcohol utilization research, and membrane research. The methanol production research activity consists of two elements: development of a pressurized oxygen gasifier and synthesis of catalytic materials to more efficiently convert synthesis gas to methanol and higher alcohols. A report is included (Finegold et al. 1981) that details the experimental apparatus and recent results obtained from the gasifier. The catalysis research is principally directed toward producing novel organometallic compounds for use as a homogeneous catalyst. The utilization research is directed toward the development of novel engine systems that use pure alcohol for fuel. Reforming methanol and ethanol catalytically to produce H/sub 2/ and CO gas for use as a fuel offers performance and efficiency advantages over burning alcohol directly as fuel in an engine. An application of this approach is also detailed at the end of this section. Another area of utilization is the use of fuel cells in transportation. In-house researchers investigating alternate electrolyte systems are exploring the direct and indirect use of alcohols in fuel cells. A workshop is being organized to explore potential applications of fuel cells in the transportation sector. The membrane research group is equipping to evaluate alcohol/water separation membranes and is also establishing cost estimation and energy utilization figures for use in alcohol plant design.

  16. Fractures and alcohol abuse - patient opinion of alcohol intervention

    DEFF Research Database (Denmark)

    Pedersen, Bolette; Alva-Jørgensen, Peter; Raffing, Rie;

    2011-01-01

    PURPOSE: To clarify patient opinions about alcohol intervention in relation to surgery before investigating the effect in a Scandinavian multi-centre randomized trial. MATERIAL AND METHODS: A qualitative study. Thirteen consecutive alcohol patients with fractures participated after informed consent....... They were interviewed during their hospital stay. The number of participants was based on the criteria of data-saturation. The analysis followed the applied qualitative framework model aimed at evaluation of specific participant needs within a larger overall project. RESULTS: All patients regarded alcohol...... intervention in relation to surgery as a good idea. They did not consider quit drinking as a major problem during their hospital stay and had all remained abstinent in this period. About half of the patients were ready or partly ready to participate in an alcohol intervention. Patient opinions...

  17. The concept of alcohol craving.

    OpenAIRE

    Katarzyna Agnieszka Iwanicka; Marcin Olajossy

    2015-01-01

    The aim of the article was to assess how the perception of alcohol craving, which is one of the symptoms of alcohol dependence, evolved, as well as how it was reflected in the diagnostic classifications. The purpose of this article was also a discussion of the models of the origins of craving, explaining the etiology of this phenomenon and the tools for measuring this concept. The concept of craving, defined as a strong need or compulsion to drink alcohol, functioned for many years, not only ...

  18. Pathogenesis of Alcoholic Liver Disease.

    Science.gov (United States)

    Dunn, Winston; Shah, Vijay H

    2016-08-01

    Alcoholic liver disease includes a broad clinical-histological spectrum from simple steatosis, cirrhosis, acute alcoholic hepatitis with or without cirrhosis to hepatocellular carcinoma as a complication of cirrhosis. The pathogenesis of alcoholic liver disease can be conceptually divided into (1) ethanol-mediated liver injury, (2) inflammatory immune response to injury, (3) intestinal permeability and microbiome changes. Corticosteroids may improve outcomes, but this is controversial and probably only impacts short-term survival. New pathophysiology-based therapies are under study, including antibiotics, caspase inhibition, interleukin-22, anakinra, FXR agonist and others. These studies provide hope for better future outcomes for this difficult disease. PMID:27373608

  19. Alcohol Dependency in Indian Dentists

    Directory of Open Access Journals (Sweden)

    Gaurav Solanki

    2012-04-01

    Full Text Available Alcohol consumption has widely increased through out the world. This all is due to a stressful life style and emotional load on a person. Dentistry is not excluded from the stress phenomenon. Dentists experience stressful situations every day, and have to deal with these in a very professional manner. The dentists participated were told about the hazard and ill-effect of alcohol consumption. There need to be a reduction in consumption of alcohol in dentistry for the upliftment of general masses as well as the dentist.

  20. The economic impact of alcohol abuse and alcoholism.

    OpenAIRE

    Burke, T. R.

    1988-01-01

    The economic effects of alcohol abuse are as damaging to the nation as the health effects, affecting the family, the community, and persons of all ages. Underaged drinking is interfering with children's development, affecting the nation's ability to respond to economic challenge in the future. The college aged may be the most difficult to educate about alcohol abuse because of drinking patterns established at an early age and susceptibility to advertising inducements. Health care costs for fa...

  1. Alcohol Advertising Bans and Alcohol Abuse: An International Perspective

    OpenAIRE

    Henry Saffer

    1989-01-01

    The purpose of this paper is to empirically examine the effect on alcohol abuse of banning broadcast advertising of alcoholic beverages. The effect of a ban cannot be studied using data from one country because the adoption of new advertising bans is an infrequent event and requires many years for adjustment. However, an international data set can be used since there is considerable variation in the use of advertising bans across countries. The data used in this study are a pooled time series...

  2. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.

    Science.gov (United States)

    Moreadith, R W; Batshaw, M L; Ohnishi, T; Kerr, D; Knox, B; Jackson, D; Hruban, R; Olson, J; Reynafarje, B; Lehninger, A L

    1984-09-01

    We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. Enzymatic assays on isolated mitochondria ruled out defects in complexes II, III, and IV of the respiratory chain. Further studies showed that the defect was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I). When ferricyanide was used as an artificial electron acceptor, complex I activity was normal, indicating that electrons from NADH could reduce the flavin mononucleotide cofactor. However, electron paramagnetic resonance spectroscopy performed on liver submitochondrial particles showed an almost total loss of the iron-sulfur clusters characteristic of complex I, whereas normal signals were noted for other mitochondrial iron-sulfur clusters. This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain.

  3. Pro187Ser Polymorphism of NAD(P)H:quinone oxidoreductase 1 and Prognosis of Non-small Cell Lung Cancer after Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Song, Si Yeol; Yoon, Sang Min; Shin, Seong Soo; Ahn, Seung Do; Lee, Jung Shin; Choi, Eun Kyung [University of Ulsan, Seoul (Korea, Republic of); Park, Heon Joo [Inha University, Incheon (Korea, Republic of); Hong, Yun Chul; Kim, Jin Hee; Park, Charn Il and others [Seoul National University, Seoul (Korea, Republic of)

    2005-07-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) has been known to function on reduction of oxidative status as a cytosolic flavoenzyme that catalyzes the electron reduction of substrates. It was reported to play a role in the prognosis of lung cancer patients treated with chemotherapy. Single nucleotide polymorphisms (SNPs) make up about ninety percent of human DNA polymorphisms, and they are a major focus of study about the individual differences for the risk of cancer and for anti-cancer treatment. A point mutation in exon 6 of the NQO1 gene is a C-to-T base pair substitution at position 609 of the NQO1 cDNA, and this codes for a proline-to-serine change at position 187 in the amino acid sequence of the protein. We hypothesized that NQO1 polymorphism could have an adverse influence on the survival of NSCLC patients treated with radiation therapy and/or surgery, and so we tried to discover whether the NQO1 polymorphism could be a predictive or prognostic marker for determining treatment outcome of radiotherapy in nonsmall cell lung cancer (NSCLC) patients.

  4. GmcA is a putative glucose-methanol-choline oxidoreductase required for the induction of asexual development in Aspergillus nidulans.

    Directory of Open Access Journals (Sweden)

    Oier Etxebeste

    Full Text Available Aspergillus nidulans asexual differentiation is induced by Upstream Developmental Activators (UDAs that include the bZIP-type Transcription Factor (TF FlbB. A 2D-PAGE/MS-MS-coupled screen for proteins differentially expressed in the presence and absence of FlbB identified 18 candidates. Most candidates belong to GO term classes involved in osmotic and/or oxidative stress response. Among these, we focused on GmcA, a putative glucose-methanol-choline oxidoreductase which is upregulated in a ΔflbB background. GmcA is not required for growth since no differences were detected in the radial extension upon deletion of gmcA. However, its activity is required to induce conidiation under specific culture conditions. A ΔgmcA strain conidiates profusely under acid conditions but displays a characteristic fluffy aconidial phenotype in alkaline medium. The absence of asexual development in a ΔgmcA strain can be suppressed, on one hand, using high concentrations of non-fermentable carbon sources like glycerol, and on the other hand, when the cMyb-type UDA TF flbD is overexpressed. Overall, the results obtained in this work support a role for GmcA at early stages of conidiophore initiation.

  5. GmcA is a putative glucose-methanol-choline oxidoreductase required for the induction of asexual development in Aspergillus nidulans.

    Science.gov (United States)

    Etxebeste, Oier; Herrero-García, Erika; Cortese, Marc S; Garzia, Aitor; Oiartzabal-Arano, Elixabet; de los Ríos, Vivian; Ugalde, Unai; Espeso, Eduardo A

    2012-01-01

    Aspergillus nidulans asexual differentiation is induced by Upstream Developmental Activators (UDAs) that include the bZIP-type Transcription Factor (TF) FlbB. A 2D-PAGE/MS-MS-coupled screen for proteins differentially expressed in the presence and absence of FlbB identified 18 candidates. Most candidates belong to GO term classes involved in osmotic and/or oxidative stress response. Among these, we focused on GmcA, a putative glucose-methanol-choline oxidoreductase which is upregulated in a ΔflbB background. GmcA is not required for growth since no differences were detected in the radial extension upon deletion of gmcA. However, its activity is required to induce conidiation under specific culture conditions. A ΔgmcA strain conidiates profusely under acid conditions but displays a characteristic fluffy aconidial phenotype in alkaline medium. The absence of asexual development in a ΔgmcA strain can be suppressed, on one hand, using high concentrations of non-fermentable carbon sources like glycerol, and on the other hand, when the cMyb-type UDA TF flbD is overexpressed. Overall, the results obtained in this work support a role for GmcA at early stages of conidiophore initiation. PMID:22792266

  6. DnaK dependence of mutant ethanol oxidoreductases evolved for aerobic function and protective role of the chaperone against protein oxidative damage in Escherichia coli

    Science.gov (United States)

    Echave, Pedro; Esparza-Cerón, M. Angel; Cabiscol, Elisa; Tamarit, Jordi; Ros, Joaquim; Membrillo-Hernández, Jorge; Lin, E. C. C.

    2002-01-01

    The adhE gene of Escherichia coli encodes a multifunctional ethanol oxidoreductase (AdhE) that catalyzes successive reductions of acetyl-CoA to acetaldehyde and then to ethanol reversibly at the expense of NADH. Mutant JE52, serially selected for acquired and improved ability to grow aerobically on ethanol, synthesized an AdhEA267T/E568K with two amino acid substitutions that sequentially conferred improved catalytic properties and stability. Here we show that the aerobic growth ability on ethanol depends also on protection of the mutant AdhE against metal-catalyzed oxidation by the chaperone DnaK (a member of the Hsp70 family). No DnaK protection of the enzyme is evident during anaerobic growth on glucose. Synthesis of DnaK also protected E. coli from H2O2 killing under conditions when functional AdhE is not required. Our results therefore suggest that, in addition to the known role of protecting cells against heat stress, DnaK also protects numerous kinds of proteins from oxidative damage. PMID:11917132

  7. Seasonal dynamics of anammox bacteria in estuarial sediment of the Mai Po Nature Reserve revealed by analyzing the 16S rRNA and hydrazine oxidoreductase (hzo) genes.

    Science.gov (United States)

    Li, Meng; Cao, Huiluo; Hong, Yi-Guo; Gu, Ji-Dong

    2011-01-01

    The community and population dynamics of anammox bacteria in summer (wet) and winter (dry) seasons in estuarial mudflat sediment of the Mai Po Nature Reserve were investigated by 16S rRNA and hydrazine oxidoreductase (hzo) genes. 16S rRNA phylogenetic diversity showed that sequences related to 'Kuenenia' anammox bacteria were presented in summer but not winter while 'Scalindua' anammox bacteria occurred in both seasons and could be divided into six different clusters. Compared to the 16S rRNA genes, the hzo genes revealed a relatively uniform seasonal diversity, with sequences relating to 'Scalindua', 'Anammoxoglobus', and planctomycete KSU-1 found in both seasons. The seasonal specific bacterial groups and diversity based on the 16S rRNA and hzo genes indicated strong seasonal community structures in estuary sediment of this site. Furthermore, the higher abundance of hzo genes in summer than winter indicates clear seasonal population dynamics. Combining the physicochemical characteristics of estuary sediment in the two seasons and their correlations with anammox bacteria community structure, we proposed the strong seasonal dynamics in estuary sediment of Mai Po to be due to the anthropogenic and terrestrial inputs, especially in summer, which brings in freshwater anammox bacteria, such as 'Kuenenia', interacting with the coastal marine anammox bacteria 'Scalindua'.

  8. Localization and Function of the Membrane-bound Riboflavin in the Na+-translocating NADH:Quinone Oxidoreductase (Na+-NQR) from Vibrio cholerae*

    Science.gov (United States)

    Casutt, Marco S.; Huber, Tamara; Brunisholz, René; Tao, Minli; Fritz, Günter; Steuber, Julia

    2010-01-01

    The sodium ion-translocating NADH:quinone oxidoreductase (Na+-NQR) from the human pathogen Vibrio cholerae is a respiratory membrane protein complex that couples the oxidation of NADH to the transport of Na+ across the bacterial membrane. The Na+-NQR comprises the six subunits NqrABCDEF, but the stoichiometry and arrangement of these subunits are unknown. Redox-active cofactors are FAD and a 2Fe-2S cluster on NqrF, covalently attached FMNs on NqrB and NqrC, and riboflavin and ubiquinone-8 with unknown localization in the complex. By analyzing the cofactor content and NADH oxidation activity of subcomplexes of the Na+-NQR lacking individual subunits, the riboflavin cofactor was unequivocally assigned to the membrane-bound NqrB subunit. Quantitative analysis of the N-terminal amino acids of the holo-complex revealed that NqrB is present in a single copy in the holo-complex. It is concluded that the hydrophobic NqrB harbors one riboflavin in addition to its covalently attached FMN. The catalytic role of two flavins in subunit NqrB during the reduction of ubiquinone to ubiquinol by the Na+-NQR is discussed. PMID:20558724

  9. Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content.

    Science.gov (United States)

    Shirasaka, Y; Chaudhry, A S; McDonald, M; Prasad, B; Wong, T; Calamia, J C; Fohner, A; Thornton, T A; Isoherranen, N; Unadkat, J D; Rettie, A E; Schuetz, E G; Thummel, K E

    2016-08-01

    Large interindividual variability has been observed in the metabolism of CYP2C19 substrates in vivo. The study aimed to evaluate sources of this variability in CYP2C19 activity, focusing on CYP2C19 diplotypes and the cytochrome P450 oxidoreductase (POR). CYP2C19 gene analysis was carried out on 347 human liver samples. CYP2C19 activity assayed using human liver microsomes confirmed a significant a priori predicted rank order for (S)-mephenytoin hydroxylase activity of CYP2C19*17/*17 > *1B/*17 > *1B/*1B > *2A/*17 > *1B/*2A > *2A/*2A diplotypes. In a multivariate analysis, the CYP2C19*2A allele and POR protein content were associated with CYP2C19 activity. Further analysis indicated a strong effect of the CYP2C19*2A, but not the *17, allele on both metabolic steps in the conversion of clopidogrel to its active metabolite. The present study demonstrates that interindividual variability in CYP2C19 activity is due to differences in both CYP2C19 protein content associated with gene diplotypes and the POR concentration.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.58. PMID:26323597

  10. Flavodoxin cofactor binding induces structural changes that are required for protein-protein interactions with NADP(+) oxidoreductase and pyruvate formate-lyase activating enzyme.

    Science.gov (United States)

    Crain, Adam V; Broderick, Joan B

    2013-12-01

    Flavodoxin (Fld) conformational changes, thermal stability, and cofactor binding were studied using circular dichroism (CD), isothermal titration calorimetry (ITC), and limited proteolysis. Thermodynamics of apo and holo-Fld folding were examined to discern the features of this important electron transfer protein and to provide data on apo-Fld. With the exception of fluorescence and UV-vis binding experiments with its cofactor flavin mononucleotide (FMN), apo-Fld is almost completely uncharacterized in Escherichia coli. Fld is more structured when the FMN cofactor is bound; the association is tight and driven by enthalpy of binding. Surface plasmon resonance binding experiments were carried out under anaerobic conditions for both apo- and holo-Fld and demonstrate the importance of structure and conformation for the interaction with binding partners. Holo-Fld is capable of associating with NADP(+)-dependent flavodoxin oxidoreductase (FNR) and pyruvate formate-lyase activating enzyme (PFL-AE) whereas there is no detectable interaction between apo-Fld and either protein. Limited proteolysis experiments were analyzed by LC-MS to identify the regions in Fld that are involved in conformation changes upon cofactor binding. Docking software was used to model the Fld/PFL-AE complex to understand the interactions between these two proteins and gain insight into electron transfer reactions from Fld to PFL-AE.

  11. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.

    Science.gov (United States)

    Moreadith, R W; Batshaw, M L; Ohnishi, T; Kerr, D; Knox, B; Jackson, D; Hruban, R; Olson, J; Reynafarje, B; Lehninger, A L

    1984-09-01

    We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. Enzymatic assays on isolated mitochondria ruled out defects in complexes II, III, and IV of the respiratory chain. Further studies showed that the defect was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I). When ferricyanide was used as an artificial electron acceptor, complex I activity was normal, indicating that electrons from NADH could reduce the flavin mononucleotide cofactor. However, electron paramagnetic resonance spectroscopy performed on liver submitochondrial particles showed an almost total loss of the iron-sulfur clusters characteristic of complex I, whereas normal signals were noted for other mitochondrial iron-sulfur clusters. This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain. PMID:6432847

  12. Involvement of Xanthine Oxidoreductase-related Oxidative Stress in a Dermatophagoides farinae-induced Asthma Model of NC/Nga Mice.

    Science.gov (United States)

    Setiawan, Heri; Nagaoka, Kenjiro; Kubo, Masayuki; Fujikura, Yoshihisa; Ogino, Keiki

    2016-06-01

    Oxidative stress is widely known to play a role in asthma. However, the contribution of xanthine oxidoreductase (XOR) as a source of the superoxide anion radical (O2-) in oxidative stress associated with asthma has not yet been examined in detail. Here we investigated pathophysiological changes in XOR in an experimental model of asthma induced by the house dust mite Dermatophagoides farinae (Df). In the lungs of Df-treated mice, the production of O2 - from XOR increased and the nitrite concentrations decreased, whereas the protein expression of XOR remained unchanged. Moreover, the protein expression levels of XOR and the hydrogen peroxide (H2O2) concentrations in bronchoalveolar lavage fluid (BALF) were higher in the Df-treated mice than in saline-treated mice. Immunohistochemically, although XOR was highly localized in the bronchial epithelial cells of the saline-treated mice, immunostaining for XOR was absent in the bronchial epithelium of Df-treated mice. These results suggest that oxidative stress is up-regulated by increases in the conversion of the dehydrogenase form (xanthine dehydrogenase; XDH) of XOR to the oxidase form (xanthine oxidase; XOD). PMID:27339206

  13. Analysis of experimental errors in bioprocesses. 1. Production of lactobionic acid and sorbitol using the GFOR (glucose-fructose oxidoreductase) enzyme from permeabilized cells of Zymomonas mobilis.

    Science.gov (United States)

    Severo, João B; Pinto, José C; Ferraz, Helen C; Alves, Tito L M

    2011-09-01

    The proper determination of experimental errors in bioprocesses can be very important because experimental errors can exert a major impact on the analysis of experimental results. Despite this, the effect of experimental errors on the analysis of bioprocess data has been largely overlooked in the literature. For this reason, we performed detailed statistical analyses of experimental errors obtained during the production of lactobionic acid and sorbitol in a system utilizing as catalyst the GFOR (glucose-fructose oxidoreductase) enzyme from permeabilized cells of the bacteria Zymomonas mobilis. The magnitude of the experimental errors thus obtained were then correlated with the process operation conditions and with the composition of the culture media used for bacterial growth. It is shown that experimental errors can depend very significantly on the operation conditions and affect the interpretation of available experimental data. More specifically, in this study, experimental errors depended on the nutritional supplements added to the cultivation medium, the inoculation process, and the reaction time, which may be of fundamental importance for actual process development. The results obtained also indicate, for the first time, that GFOR activity can be affected by the composition of the medium in which cells are cultivated.

  14. Characterization and expression of a cDNA, AmphiSDHD,encoding the amphioxus cytochrome b small subunit in mitochondrial succinate-ubiquinone oxidoreductase

    Institute of Scientific and Technical Information of China (English)

    MA Lifang; ZHANG Shicui; ZHUANG Zhimeng; LIU Zhenhui; LI Hongyan; XIA Jianjun

    2005-01-01

    In this study, an amphioxus cDNA, AmphiSDHD, encoding the cytochrome b small subunit in mitochondrial succinate-ubiquinone oxidoreductase, was isolated from the gut cDNA library of amphioxus Branchiostoma belcheri tsingtauense. It is 1429 bp in length, with an open reading frame of 465 bp coding for a protein of 154 amino acids. The deduced protein contains a mitochondrial targeting presequence of 65 amino acids rich in basic residues like arginine and hydroxy residues such as serine and threonine. Alignment of the amino acid sequences of AmphiSDHD and other eukaryotic SDHD proteins showed that AmphiSDHD has three transmembrane segments, and includes two histidine residues in the second transmembrane segment that are the putative binding sites for the heme b molecule. The phylogenetic tree constructed suggests that AmphiSDHD appears more closely related to vertebrate SDHD proteins than invertebrate ones. Northern blotting demonstrated that AmphiSDHD is ubiquitously expressed in amphioxus, being in line with the fact that SDHD is a house-keeping protein.

  15. Improving the Biodesulfurization of Crude Oil and Derivatives: A QM/MM Investigation of the Catalytic Mechanism of NADH-FMN Oxidoreductase (DszD).

    Science.gov (United States)

    Sousa, Sérgio F; Sousa, Joana F M; Barbosa, Ana C C; Ferreira, Cleide E; Neves, Rui P P; Ribeiro, António J M; Fernandes, Pedro A; Ramos, Maria João

    2016-07-14

    The development of biocatalytic desulfurization strategies of petroleum and its derivatives could result in more economic alternatives than the widely used chemical desulfurization. The organism Rhodococcus erythropolis IGTS8 has been shown to metabolize organic sulfur compounds through a mechanism known as 4S pathway, which involves four enzymes (DszA, DszB, DszC, and DszD) and has been explored in biodesulfurization. Here we have applied QM/MM methods to study the catalytic mechanism of the enzyme DszD, a NADH-FMN oxidoreductase that occupies a central place on the 4S pathway by catalyzing the formation of the FMNH2 that is used by the two monooxynases in the cycle: DszA and DszC. In addition, to clarify the catalytic mechanism of this enzyme, this study analyzed in detail the role played by the active site Thr residue and of Asn and Ala enzyme mutants. The results help to explain previous experimental evidence and suggest new strategies for improving biodesulfurization through an increase in the activity of DszD. PMID:27128525

  16. 21 CFR 173.240 - Isopropyl alcohol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Isopropyl alcohol. 173.240 Section 173.240 Food and..., Lubricants, Release Agents and Related Substances § 173.240 Isopropyl alcohol. Isopropyl alcohol may be... label of the hops extract specifies the presence of the isopropyl alcohol and provides for the use...

  17. Children's Alcohol Initiation: An Analytic Overview

    Science.gov (United States)

    Ward, Bernadette; Snow, Pamela; Aroni, Rosalie

    2010-01-01

    Many parents support the "supervised introduction" of alcohol to children. While initiation to regular alcohol consumption in early adolescence has been linked with alcohol-related problems in adult life, the findings from these studies cannot be extrapolated to early childhood. The definition of initiation to alcohol in early childhood is often…

  18. Towards the Prevention of Alcohol Abuse

    Science.gov (United States)

    Facy, FranCoise; Rabaud, Myriam

    2006-01-01

    Mortality resulting from alcohol abuse in young French people is too high in spite of prevention campaigns for road safety in particular. There are problems in identifying alcohol abuse in young people in preventive medicine or alcohol care services. This study was carried out in alcohol centres; data from patients under 25 are analysed and…

  19. Syndrome Analysis: Chronic Alcoholism in Adults.

    Science.gov (United States)

    Pendorf, James E.

    1990-01-01

    Provides outline narrative of most possible outcomes of regular heavy alcohol use, regular alcohol abuse, or chronic alcoholism. A systems analysis approach is used to expose conditions that may result when a human organism is subjected to excessive and chronic alcohol consumption. Such an approach illustrates the detrimental effects which alcohol…

  20. Alcohol and Kids: Facing Our Problem.

    Science.gov (United States)

    Long, Nicholas; And Others

    1993-01-01

    Introduces special journal issue on alcohol use among children and adolescents. Describes scope of the problem, claiming that alcohol is the most consumed drug among children and youth. Discusses possible progression in alcohol use, parents' reactions to their children using alcohol or other drugs, and effects of the media and advertising on…

  1. A prospective toxicology analysis in alcoholics

    DEFF Research Database (Denmark)

    Thomsen, Jørgen Lange; Simonsen, Kirsten Wiese; Felby, Søren;

    1997-01-01

    A prospective and comprehensive investigation was done on 73 medico–legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis...

  2. 49 CFR 382.201 - Alcohol concentration.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Alcohol concentration. 382.201 Section 382.201... ALCOHOL USE AND TESTING Prohibitions § 382.201 Alcohol concentration. No driver shall report for duty or... concentration of 0.04 or greater. No employer having actual knowledge that a driver has an alcohol...

  3. Youths and Alcohol Abuse: A Continuing Phenomenon.

    Science.gov (United States)

    Torres, Donald A.

    1982-01-01

    Defines problem drinking and alcoholism, and differentiates normal drinking escapes from alcohol abuse by teenagers and other youths. Suggests teenagers consume alcohol for a myriad of reasons and this behavior often leads to alcohol dependence which can cause interference in normal relationships with others. (Author)

  4. Cryptorchidism and maternal alcohol consumption during pregnancy

    DEFF Research Database (Denmark)

    Damgaard, Ida N; Jensen, Tina Kold; Petersen, Jørgen H;

    2007-01-01

    Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys.......Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys....

  5. Adolescent Alcohol Consumption in Romania: A Blueprint for Measuring Alcohol (mis)Use

    NARCIS (Netherlands)

    Hoof, van Joris J.; Moll, Marit

    2012-01-01

    In order to address the issues of adolescent alcohol (mis)use in Romanian cities and to develop local alcohol prevention policies comprised of interventions aimed at reducing alcohol consumption and alcohol related problems, information on the prevalence of alcohol use and relevant related topics is

  6. 77 FR 59405 - National Institute On Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-09-27

    ... HUMAN SERVICES National Institutes of Health National Institute On Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... and Alcoholism, 5635 Fishers Lane, Room 2109, Rockville, MD 20852, 301-443-8599,...

  7. 75 FR 47819 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-08-09

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... Alcoholism. The meeting will be open to the public as indicated below, with attendance limited to space... on Alcohol Abuse and Alcoholism. Date: September 22-23, 2010. Closed: September 22, 2010, 5:30...

  8. Alcohol Consumption and Harm among Adolescents in Sweden: Is Smuggled Alcohol More Harmful?

    Science.gov (United States)

    Svensson, Johan

    2012-01-01

    As a consequence of Sweden joining the European Union, privately imported alcohol is increasingly sold within illegal contexts (i.e., smuggled alcohol). One implication of the smuggled alcohol is that alcohol becomes more available to underage drinkers. In the Swedish debate, smuggled alcohol has been formulated as a youth problem. The aim of this…

  9. 76 FR 22717 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-04-22

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Federal Domestic Assistance Program Nos. 93.271, Alcohol Research Career Development Awards for...

  10. 77 FR 24726 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2012-04-25

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The...: Abraham P. Bautista, Ph.D., Executive Secretary, National Institute on Alcohol Abuse &...

  11. 75 FR 80511 - National Institute on Alcohol Abuse And Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-12-22

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse And Alcoholism; Notice....C. App), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and... on Alcohol Abuse and Alcoholism. Date: February 16-17, 2011. Closed: February 16, 2011, 5:30 p.m....

  12. 76 FR 44596 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-07-26

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis.... Contact Person: Beata Buzas, PhD, Scientific Review Officer, National Institute on Alcohol Abuse...

  13. 78 FR 13361 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-02-27

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis.... 93.273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: February 21,...

  14. 78 FR 71628 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Science.gov (United States)

    2013-11-29

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice....), notice is hereby given of a meeting of the National Advisory Council on Alcohol Abuse and Alcoholism. The.... Agenda: To review and evaluate grant applications. Place: National Institute on Alcohol Abuse...

  15. 78 FR 37836 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-06-24

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Program No. 93.273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: June 18,...

  16. 78 FR 75927 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-12-13

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis.... Agenda: To review and evaluate grant applications. Place: National Institute on Alcohol Abuse...

  17. 76 FR 44597 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-07-26

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... of Federal Domestic Assistance Program Nos. 93.271, Alcohol Research Career Development Awards...

  18. 77 FR 70171 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-11-23

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review.... Contact Person: Beata Buzas, Ph.D. Scientific Review Officer, National Institute on Alcohol Abuse...

  19. 78 FR 66015 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-11-04

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis.... Agenda: To review and evaluate grant applications Place: National Institute on Alcohol Abuse...

  20. 75 FR 42449 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-21

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis... Person: Philippe Marmillot, PhD, Scientific Review Officer, National Institute on Alcohol Abuse...

  1. 76 FR 22715 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-04-22

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Federal Domestic Assistance Program Nos. 93.271, Alcohol Research Career Development Awards for...

  2. 75 FR 42756 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-22

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Advisory Council on Alcohol Abuse and Alcoholism. Date... Person: Abraham P. Bautista, PhD, Executive Secretary, National Institute on Alcohol Abuse and...

  3. 77 FR 26770 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-05-07

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis....271, Alcohol Research Career Development Awards for Scientists and Clinicians; 93.272,...

  4. 75 FR 36660 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-06-28

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Program Nos. 93.271, Alcohol Research Career Development Awards for Scientists and Clinicians;...

  5. 78 FR 63484 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-10-24

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... 2013. (Catalogue of Federal Domestic Assistance Program No. 93.273, Alcohol Research Programs;...

  6. 76 FR 2129 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-01-12

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis Panel, ``Review of the Prenatal Alcohol in Sudden Infant Death Syndrome And Stillbirth (PASS)...

  7. 78 FR 37835 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-06-24

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... No. 93.273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: June 18,...

  8. 78 FR 17680 - National Institute on Alcohol Abuse and Alcoholism; Closed Meeting

    Science.gov (United States)

    2013-03-22

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Closed... of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis Panel, NIAAA... . (Catalogue of Federal Domestic Assistance Program Nos. 93.273, Alcohol Research Programs; National...

  9. 78 FR 41938 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-12

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review.... Contact Person: Beata Buzas, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse...

  10. 78 FR 37837 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-06-24

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis....273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: June 18, 2013. Carolyn...

  11. 78 FR 12072 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-02-21

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... . (Catalogue of Federal Domestic Assistance Program Nos. 93.273, Alcohol Research Programs; National...

  12. 77 FR 72873 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-12-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Domestic Assistance Program Nos. 93.273, Alcohol Research Programs; National Institutes of Health,...

  13. 78 FR 10185 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-02-13

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis....273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: February 7, 2013. Carolyn...

  14. 78 FR 63483 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-10-24

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... of personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special... shutdown of October 2013. (Catalogue of Federal Domestic Assistance Program No. 93.273, Alcohol...

  15. Low-Pressure Alcohol Distillation

    Science.gov (United States)

    Frazier, D. O.; Zur Burg, F. W.; Cody, J. C.

    1984-01-01

    Heat requirements lowered for process. Temperature requirements lowered enough to make solar heat absorbed by flat-plate collectors feasible energy source. Alcohol produced without adding other solvents, eliminating need for dehydration or hydrocarbon stripping as final step.

  16. Erectile impotence in chronic alcoholics.

    Science.gov (United States)

    Tan, E T; Johnson, R H; Lambie, D G; Vijayasenan, M E; Whiteside, E A

    1984-01-01

    Erectile impotence is a common complaint in alcoholics, but its mechanism is unknown. We have studied nocturnal penile erection in 13 alcoholics who complained of impotence. Seven had normal erections and their impotence was therefore psychogenic. Six were found to have diminished or absent nocturnal erections. Plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were elevated in this latter group, with the exception of one patient who had only raised FSH. They also had more evidence of neurological damage than the other seven alcoholics, and two had evidence of damage to the parasympathetic nervous system. Investigation of erection during sleep in alcoholic patients with impotence may be useful in differentiating clinically between patients with psychogenic causes and patients with organic causes of impotence.

  17. Cancer morbidity in alcohol abusers

    DEFF Research Database (Denmark)

    Tønnesen, H; Møller, Henrik; Andersen, J R;

    1994-01-01

    = 1.5; 95% CI 1.3-1.8). Significantly increased incidences were found of cancer in the tongue, mouth, pharynx, oesophagus, liver, larynx, lung and pleura and secondary cancer. The women had significantly increased risk of cervical cancer (RR = 2.0; 95% CI 1.2-3.0). The men developed prostatic cancer...... and the liver are confirmed. In addition, this study indicates an increased occurrence of cancer of the prostate gland, pleura and uterine cervix in alcohol abusers.......Data on the association between alcohol abuse and cancer morbidity are scarce in large cohorts of non-hospitalised alcoholic men and women. Of 18,368 alcohol abusers who entered an outpatient clinic in Copenhagen during 1954-87, 18,307 were followed and their cancer incidence was compared...

  18. Kids and Alcohol (For Parents)

    Science.gov (United States)

    ... Abuse Alcohol interferes with a person's perception of reality and ability to make good decisions. This can ... that kids know and understand. For example, watching TV with your child can provide a chance to ...

  19. Neurobiological Basis of Alcohol Addiction

    Directory of Open Access Journals (Sweden)

    Milagros Lisset León Regal

    2014-02-01

    Full Text Available Alcoholism is a serious social problem due to its impact on individual and collective health. In order to provide an update on the latest findings that explain the development and symptoms of alcohol addiction, the short and long term changes that this disorder causes in the central nervous system are shown in this paper. A total of 52 information sources were consulted, including 43 journal articles, 4 books and statistical reports. The main network managers were used. The interaction of ethanol with various structures of the neuronal membrane affects the cytoarchitecture and brain function associated with the reward system, motor processing, learning and memory, resulting in the development of alcohol dependence. In addition, ethanol-induced changes in excitation/inhibition explain the phenomena of alcohol tolerance and withdrawal.

  20. Alcohol in Greenland 1951-2010

    DEFF Research Database (Denmark)

    Aage, Hans

    2012-01-01

    Background. Fluctuations in alcohol consumption in Greenland have been extreme since alcohol became available to the Greenland Inuit in the 1950s, increasing from low levels in the 1950s to very high levels in the 1980s about twice as high as alcohol consumption in Denmark. Since then, consumption...... has declined, and current consumption is slightly below alcohol consumption in Denmark, while alcohol prices are far above Danish prices. Objective. Description of historical trends and possible causal connections of alcohol prices, alcohol consumption and alcohol-related mortality in Greenland 1951......-2010 as a background for the evaluation of the impact of various types of policy. Design. Time series for Greenland 1951-2010 for alcohol prices, consumption and mortality are compiled, and variation and correlations are discussed in relation to various policies aimed at limiting alcohol consumption. Corresponding...

  1. The Burden of Alcohol Use

    OpenAIRE

    White, Aaron; Hingson, Ralph

    2014-01-01

    Research shows that multiple factors influence college drinking, from an individual’s genetic susceptibility to the positive and negative effects of alcohol, alcohol use during high school, campus norms related to drinking, expectations regarding the benefits and detrimental effects of drinking, penalties for underage drinking, parental attitudes about drinking while at college, whether one is member of a Greek organization or involved in athletics, and conditions within the larger community ...

  2. Alcohol Poisoning Deaths PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2015-01-06

    This 60 second Public Service Announcement is based on the January 2015 CDC Vital Signs report. In the United States, an average of six people die every day from alcohol poisoning. Learn what you can do to prevent binge drinking and alcohol poisoning.  Created: 1/6/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 1/6/2015.

  3. Drug and alcohol task force

    International Nuclear Information System (INIS)

    Worker absenteeism due to substance abuse costs the Alberta economy approximately $720 million a year. It is estimated that 20 per cent of all drivers in fatal crashes were using alcohol, and the use of cannabis and cocaine in Alberta has more than doubled over the last 15 years. In addition, 1 in 10 Alberta workers have reported using alcohol while at work and 4 per cent have reported using alcohol 4 hours prior to coming to work during the previous 12 months. In an effort to ensure appropriate health and safety for workers in the Canadian petroleum industry, 6 trade associations in the sector have joined together as the Enform Alcohol and Drug Initiative and are now working to develop a common approach to drug and alcohol guidelines and workplace rules. The task group will determine if existing policies and guidelines are sufficient to ensure a safe workplace and will consider standardizing the testing, application and rehabilitation of workers with respect to the use of drugs and alcohol. In the past, disciplinary actions have often been reversed because employers have not been consistent or did not follow established alcohol and drug policies or test to specific standards. Various work rules for inappropriate alcohol and drug use were reviewed, as well as education and communication strategies regarding policy content. Standards for testing criteria were discussed, as well as issues concerning duty-to-accommodate circumstances. An excerpt of concentration standards was presented. It was concluded that a matrix for companies to assess and determine safety sensitive positions is needed. refs., tabs., figs

  4. Drug and alcohol task force

    Energy Technology Data Exchange (ETDEWEB)

    Gordey, T. [ConocoPhillips Canada Resources Corp., Calgary, AB (Canada); Sunstrum, M. [Enform, Calgary, AB (Canada)

    2006-07-01

    Worker absenteeism due to substance abuse costs the Alberta economy approximately $720 million a year. It is estimated that 20 per cent of all drivers in fatal crashes were using alcohol, and the use of cannabis and cocaine in Alberta has more than doubled over the last 15 years. In addition, 1 in 10 Alberta workers have reported using alcohol while at work and 4 per cent have reported using alcohol 4 hours prior to coming to work during the previous 12 months. In an effort to ensure appropriate health and safety for workers in the Canadian petroleum industry, 6 trade associations in the sector have joined together as the Enform Alcohol and Drug Initiative and are now working to develop a common approach to drug and alcohol guidelines and workplace rules. The task group will determine if existing policies and guidelines are sufficient to ensure a safe workplace and will consider standardizing the testing, application and rehabilitation of workers with respect to the use of drugs and alcohol. In the past, disciplinary actions have often been reversed because employers have not been consistent or did not follow established alcohol and drug policies or test to specific standards. Various work rules for inappropriate alcohol and drug use were reviewed, as well as education and communication strategies regarding policy content. Standards for testing criteria were discussed, as well as issues concerning duty-to-accommodate circumstances. An excerpt of concentration standards was presented. It was concluded that a matrix for companies to assess and determine safety sensitive positions is needed. refs., tabs., figs.

  5. Detection of alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Harriet Gordon

    2001-01-01

    @@ INTRODUCTION Alcohol has been used in society over centuries and all over the world for its mood-lifting properties and taste. It is probably ,however ,the commonest drug of abuse world-wide and unfortunately causes considerable morbidity, mortality and social disruption .In 1990 the cost tl the USA was more than $ 100 billion and 100 000 lives. The relationship between alcohol and mankind is well documented from the earliest tines .

  6. Interpersonal dependency in alcoholic and obese men.

    Science.gov (United States)

    Mills, J K

    1995-06-01

    While psychological conflict about dependency needs of alcoholic and obese persons has been widely observed, few studies have examined differences in dependency characteristics between these clinical groups. The Interpersonal Dependency Inventory was administered to 22 alcoholic and 8 morbidly obese men in intensive treatment for alcohol and obesity. The original hypothesis that alcoholic and obese men would show similar dependency needs was supported. Dependency correlates of personality may serve as useful predictor variables in the clinical treatment of alcoholic and obese persons.

  7. Pathophysiology of alcoholic pancreatitis: An overview

    Institute of Scientific and Technical Information of China (English)

    Parimal Chowdhury; Priya Gupta

    2006-01-01

    Use of alcohol is a worldwide habit regardless of socioeconomic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented.

  8. Perspectives on alcohol consumption in older adults

    OpenAIRE

    Immonen, Sirpa

    2012-01-01

    Alcohol use plays a part in the life of older adults, and can be assumed to be increasingly prominent in the future as the baby boomers age. Understanding alcohol consumption patterns and factors associated with risky drinking in the general population of older adults aids in detecting older adults who may suffer from the hazardous use of alcohol or alcohol use disorders. The present study assessed some issues in alcohol consumption among older adults: the prevalence of consumption and a...

  9. [Concentration of endogenous ethanol and alcoholic motivation].

    Science.gov (United States)

    Burov, Iu V; Treskov, V G; Kampov-Polevoĭ, A B; Kovalenko, A E; Rodionov, A P

    1983-11-01

    Trials with patients suffering from stage II chronic alcoholism and normal test subjects as well as experiments made on male C57BL mice (with genetically determined alcoholic motivation) and CBA mice (with genetically determined alcoholic aversion) and random-bred male rats with different levels of initial alcoholic motivation have shown the presence of reverse proportional dependence between blood plasma endogenous ethanol and alcoholic motivation.

  10. Grain alcohol study: summary

    Energy Technology Data Exchange (ETDEWEB)

    The study has concentrated upon a detailed examination of all considerations involved in the production, use, and marketing of ethyl alcohol (Ethanol) as produced from the fermentation of agricultural grains. Each parameter was examined in the light of current energy markets and trends; new sources and technological, and processes for fermentation, the capability of the agricultural industry to support fermentaton demand; the optimization of value of agricultureal crops; and the efficiencies of combining related industries. Anhydrous (200 proof) ethanol makes an excellent blending component for all present automotive fuels and an excellent octane additive for unleaded fuels in proportions up to 35% without requiring modifications to current engines. There is no difference between ethanol produced by fermentation and ethanol produced synthetically from petroleum. The decision to produce ethanol one way or the other is purely economic. The agricultural industry can support a major expansion in the fermentation industry. The residue (distillers grains) from the fermentation of corn for ethanol is an excellent and economical feed for livestock and poultry. A reliable supply of distillers grains can assist in making the large beef feedlot operations more economically viable. The source materials, fuels, products and by-products of an ethanol plant, beef feedlot, gas biodigester plant, municipal waste recovery plant and a steam generated electrical plant are interrelated and mutually beneficial for energy efficiencies and economic gains when co-located. The study concludes that the establishment of such agricultural-environment industrial energy complexes, would provide a broad range of significant benefits to Indiana.

  11. Grain alcohol study: summary

    Energy Technology Data Exchange (ETDEWEB)

    The study has concentrated upon a detailed examination of all considerations involved in the production, use, and marketing of ethyl alcohol (ethanol) as produced from the fermentation of agricultural grains. Each parameter was examined in the light of current energy markets and trends; new sources and technological, and processes for fermentation, the capability of the agricultural industry to support fermentation demand; the optimizaton of value of agricultural crops; and the efficiencies of combining related industries. Ahydrous (200 proof) ethanol makes an excellent blending component for all present automotive fuels and an excellent octane additive for unleaded fuels in proportions up to 35% without requiring modifications to current engines. There is no difference between ethanol produced by fermentation and ethanol produced synthetically from petroleum. The decision to produce ethanol one way or the other is purely economic. The agricultural industry can support a major expansion in the fermentation industry. The residue (distillers grains) from the fermentation of corn for ethanol is an excellent and economical feed for livestock and poultry. A reliable supply of distillers grain can assist in making the large beef feedlot operations more economically viable. The source materials, fuels, products and by-products of an ethanol plant, beef feedlot, gas biodigester plant, municipal waste recovery plant and a steam generated electrical plant are interrelated and mutually beneficial for energy efficiencies and economic gains when co-located. The study concludes that the establishment of such agricultural- environment industrial energy complexes, would provide a broad range of significant benefits to Indiana.

  12. Biomarkers of chronic alcohol misuse

    Directory of Open Access Journals (Sweden)

    Gonzalo P

    2014-01-01

    Full Text Available Philippe Gonzalo,1 Sylvie Radenne,2 Sylvie Gonzalo31Laboratoire de Biochimie, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France; 2Service d'Hépatologie-Gastroentérologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France; 3Laboratoire Biomnis, Lyon, FranceAbstract: Biological markers of chronic alcoholism can be divided into two groups: direct and indirect markers. Direct markers (mainly blood or serum and urine ethanol, ethylglucuronide, ethyl sulfate, and phosphatidylethanol directly track the intake of alcohol and vary in their sensitivity and kinetics of appearance and clearance. Indirect markers (mean corpuscular volume,γ-glutamyl transferase, alanine aminotransferase and aspartate aminotransferase, and carbohydrate-deficient transferrin are biological parameters that are influenced by a steady and significant alcohol intake. We discuss the values of these tests and the relevance of their prescriptions for the clinical evaluation of heavy drinking. We indicate, when known, the pathophysiological mechanism of their elevations. We also discuss the amount and time of alcohol consumption required to give a positive result and the duration of abstinence required for the return to normal values. The forensic use of these biomarkers will not be considered in this review.Keywords: alcoholism, biomarker, CDT, relapse, alcohol-induced liver disease

  13. Psychoanalytic treatment of psychological addiction to alcohol (alcohol abuse).

    Science.gov (United States)

    Johnson, Brian

    2011-01-01

    The DSM-V Committee plans to abolish the distinction between Alcohol Abuse and Alcohol Dependence (dsm5.org). The author presents a case report as a proof of concept that this distinction should be retained. The author has asserted that Alcohol Abuse is a purely psychological addiction, while Alcohol Dependence involves capture of the ventral tegmental dopaminergic SEEKING system (Johnson, 2003). In psychological addiction the brain can be assumed to function normally, and ordinary psychoanalytic technique can be followed. For the patient described, transference interpretation was the fundamental key to recovery. Alcoholic drinking functioned to prevent this man from remembering overwhelming childhood events; events that were also lived out in his current relationships. Murders that occurred when he was a child were hidden in a screen memory. The patient had an obsessional style of relating where almost all feeling was left out of his associations. After he stopped drinking compulsively, he continued to work compulsively. The maternal transference had to be enacted and then interpreted in order for overwhelming memories to be allowed into conscious thought. After psychoanalysis, the patient resumed drinking and worked a normal schedule that allowed more fulfilling relationships. He had no further symptoms of distress from drinking over a 9-year followup. This case illustrates that Alcohol Abuse is a purely psychological illness, that it does not have the brain changes typical of Alcohol Dependence. Combining epidemiological, neurobiological, longitudinal, and psychoanalytic observations would allow multiple sources of information to be used in creating diagnostic categories. Losing details of human behavior by relying only on epidemiological studies is likely to cause errors in categorization of disorders. In turn, having faulty categories as the basis of further research is likely to impair identification of specific effective treatments.

  14. Alcohol and Suicide: Neurobiological and Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Leo Sher

    2006-01-01

    Full Text Available Alcohol, primarily in the form of ethyl alcohol (ethanol, has occupied an important place in the history of humankind for at least 8,000 years. In most Western societies, at least 90% of people consume alcohol at some time during their lives, and 30% or more of drinkers develop alcohol-related problems. Severe alcohol-related life impairment, alcohol dependence (alcoholism, is observed at some time during their lives in about 10% of men and 3—5% of women. An additional 5—10% of each sex develops persistent, but less intense, problems that are diagnosed as alcohol abuse. It this review, neurobiological aspects of suicidal behavior in alcoholism is discussed. In individuals with comorbid depression and alcoholism, greater serotonergic impairment may be associated with higher risk of completed suicide. Dopaminergic dysfunction may play an important role in the pathophysiology of suicidal behavior in alcoholism. Brain damage and neurobehavioral deficits are associated with alcohol use disorders and may contribute to suicidal behavior in persons with alcohol dependence or abuse. Aggression/impulsivity and alcoholism severity affect risk for suicide among individuals with alcoholism. Major depressive episodes and stressful life events particularly, partner-relationship disruptions, may precipitate suicidal behavior in individuals with alcohol use disorders. Alcohol misuse and psychosocial adversity can combine to increase stress on the person, and, thereby, potentially, increase the risk for suicidal behavior. The management of suicidal patients with alcohol use disorders is also discussed. It is to be hoped that the efforts of clinicians will reduce morbidity and mortality associated with alcohol misuse.

  15. Alcohol demand and risk preference.

    Science.gov (United States)

    Dave, Dhaval; Saffer, Henry

    2008-12-01

    Both economists and psychologists have studied the concept of risk preference. Economists categorize individuals as more or less risk-tolerant based on the marginal utility of income. Psychologists categorize individuals' propensity towards risk based on harm avoidance, novelty seeking and reward dependence traits. The two concepts of risk are related, although the instruments used for empirical measurement are quite different. Psychologists have found risk preference to be an important determinant of alcohol consumption; however economists have not included risk preference in studies of alcohol demand. This is the first study to examine the effect of risk preference on alcohol consumption in the context of a demand function. The specifications employ multiple waves from the Panel Study of Income Dynamics (PSID) and the Health and Retirement Study (HRS), which permit the estimation of age-specific models based on nationally representative samples. Both of these data sets include a unique and consistent survey instrument designed to directly measure risk preference in accordance with the economist's definition. This study estimates the direct impact of risk preference on alcohol demand and also explores how risk preference affects the price elasticity of demand. The empirical results indicate that risk preference has a significant negative effect on alcohol consumption, with the prevalence and consumption among risk-tolerant individuals being 6-8% higher. Furthermore, the tax elasticity is similar across both risk-averse and risk-tolerant individuals. This suggests that tax policies are as equally effective in deterring alcohol consumption among those who have a higher versus a lower propensity for alcohol use. PMID:19956353

  16. Diagnosis of alcoholic liver disease.

    Science.gov (United States)

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-09-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  17. Paternal alcoholism predicts the occurrence but not the remission of alcoholic drinking

    DEFF Research Database (Denmark)

    Knop, J; Penick, E C; Nickel, E J;

    2007-01-01

    examinations were performed at age 40 (n = 202) by a psychiatrist using structured interviews and DSM-III-R diagnostic criteria. RESULTS: HR subjects were significantly more likely than LR subjects to develop alcohol dependence (31% vs. 16%), but not alcohol abuse (17% vs. 15%). More subjects with alcohol...... abuse were in remission at age 40 than subjects with alcohol dependence. Risk did not predict remission from either alcohol abuse or alcohol dependence. CONCLUSION: Familial influences may play a stronger role in the development of alcoholism than in the remission or recovery from alcoholism....

  18. Relationship Between Alcohol Drinking and Alcohol-related Health Problems

    Institute of Scientific and Technical Information of China (English)

    JIA-FANG ZHANG; YUN-XIA LU; XIAO-XIA QIU; YA FANG

    2004-01-01

    Objective To study the relationship between drinking environment, attitudes and situation and alcohol-related health problems. Methods A sample of 2327 respondents was randomly collected from Wuhan, Hubei Province in China by a face-to-face interview. The structural equation modeling analysis was performed for the data collected. Results Both parents' drinking behaviors and respondents' drinking situation strongly impacted the alcohol-related problems and diseases. Friends' or peers' drinking behaviors influenced the respondents' drinking attitudes and behaviors. Males experienced more alcohol-related problems and diseases than females. Conclusions Comparatively, parents' drinking behaviors exert the most significant influence on drinkers. Therefore, it is beneficial to restrict parents' drinking behaviors for the offsprings and the whole society, and an intensive professional education in early motherhood is also necessary for Chinese women.

  19. Genetic association of NAD(P)H quinone oxidoreductase (NQO1*2) polymorphism with NQO1 levels and risk of diabetic nephropathy.

    Science.gov (United States)

    Sharma, Mohini; Mehndiratta, Mohit; Gupta, Stuti; Kalra, Om P; Shukla, Rimi; Gambhir, Jasvinder K

    2016-08-01

    NAD(P)H quinone oxidoreductase 1 (NQO1) catalyzes reactions having a cyto-protective effect against redox cycling and oxidative stress. A single base polymorphism (C/T) at nucleotide 609 of the NQO1 gene impairs the stability and function of its protein. Its role in the development of diabetic nephropathy (DN) has not been deciphered. Therefore, this study aimed to evaluate the association of NQO1*2 (rs1800566) polymorphism with plasma NQO1 levels and DN. This study screened 600 participants including healthy controls (HC), type 2 diabetes mellitus without complications (T2DM) and diabetic nephropathy (DN): 200 each for studying NQO1*2 gene polymorphism using the PCR-RFLP. Plasma NQO1 levels were measured by ELISA. Analysis of variance and logistic regression were used to evaluate the association of NQO1 polymorphism with plasma NQO1 levels and DN. The allelic frequencies of NQO1*1/NQO1*2 were 0.88/0.12 in HC, 0.765/0.235 in T2DM and 0.65/0.35 in DN. Carriers of the NQO1*2 allele had significantly lower plasma NQO1 levels (p<0.05) and revealed higher risk towards the development of DN (OR=1.717, p=0.010). NQO1*2 SNP is a functional polymorphism having a significant effect on NQO1 levels. Our results indicate that NQO1*2 genotype may increase susceptibility to DN in north Indian subjects with T2DM. PMID:27078674

  20. LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer.

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    Anamika Basu

    Full Text Available Prostate cancer (PCa mortality is driven by highly aggressive tumors characterized by metastasis and resistance to therapy, and this aggressiveness is mediated by numerous factors, including activation of stress survival pathways in the pro-inflammatory tumor microenvironment. LEDGF/p75, also known as the DFS70 autoantigen, is a stress transcription co-activator implicated in cancer, HIV-AIDS, and autoimmunity. This protein is targeted by autoantibodies in certain subsets of patients with PCa and inflammatory conditions, as well as in some apparently healthy individuals. LEDGF/p75 is overexpressed in PCa and other cancers, and promotes resistance to chemotherapy-induced cell death via the transactivation of survival proteins. We report in this study that overexpression of LEDGF/p75 in PCa cells attenuates oxidative stress-induced necrosis but not staurosporine-induced apoptosis. This finding was consistent with the observation that while LEDGF/p75 was robustly cleaved in apoptotic cells into a p65 fragment that lacks stress survival activity, it remained relatively intact in necrotic cells. Overexpression of LEDGF/p75 in PCa cells led to the upregulation of transcript and protein levels of the thiol-oxidoreductase ERp57 (also known as GRP58 and PDIA3, whereas its depletion led to ERp57 transcript downregulation. Chromatin immunoprecipitation and transcription reporter assays showed LEDGF/p75 binding to and transactivating the ERp57 promoter, respectively. Immunohistochemical analysis revealed significantly elevated co-expression of these two proteins in clinical prostate tumor tissues. Our results suggest that LEDGF/p75 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and that its overexpression in PCa leads to ERp57 upregulation. These findings are of significance in clarifying the role of the LEDGF/p75 stress survival pathway in PCa.