Sample records for gamma-glutamyl transpeptidase ggt

  1. Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

    NASA Technical Reports Server (NTRS)

    Levasseur, Regis; Barrios, Roberto; Elefteriou, Florent; Glass, Donald A 2nd; Lieberman, Michael W.; Karsenty, Gerard

    2003-01-01

    Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

  2. Variation of human intestinal gamma-glutamyl transpeptidase in ontogenetic development.

    PubMed

    Sobiech, K A; Szewczuk, A

    1977-01-01

    Activity of gamma-glutamyl transpeptidase in human intestines was measured against alpha-naphthylamide and 12 gamma-glutamyl amino acids and peptides as substrate. Distinctly altered activity was found to accompany ontogenetic development. The ratio of the transpeptidase activity tested against monoglutamyl substrates in the intestines of 7-month fetuses, newborns and adults was 15:1:4, whereas the ratio of gamma-glutamyl cyclotransferase activities in the same age groups was 1-0:1-2:1-6. Distinct differences were found in resistance to heating, sensitivity to L-serine plus borate, and other effectors, and electrophoretic mobility, between fetal gamma-glutamyl transpeptidase and the enzyme from adults, which supports the hypothesis of existence of two forms of the enzyme in the human intestines. The results suggest involvement of gamma-glutamyl transpeptidase in the pathomechanism of celiakia in children.

  3. A gamma-glutamyl transpeptidase-independent pathway of glutathione catabolism to glutamate via 5-oxoproline in Arabidopsis.

    PubMed

    Ohkama-Ohtsu, Naoko; Oikawa, Akira; Zhao, Ping; Xiang, Chengbin; Saito, Kazuki; Oliver, David J

    2008-11-01

    The degradation pathway of glutathione (GSH) in plants is not well understood. In mammals, GSH is predominantly metabolized through the gamma-glutamyl cycle, where GSH is degraded by the sequential reaction of gamma-glutamyl transpeptidase (GGT), gamma-glutamyl cyclotransferase, and 5-oxoprolinase to yield glutamate (Glu) and dipeptides that are subject to peptidase action. In this study, we examined if GSH is degraded through the same pathway in Arabidopsis (Arabidopsis thaliana) as occurs in mammals. In Arabidopsis, the oxoprolinase knockout mutants (oxp1-1 and oxp1-2) accumulate more 5-oxoproline (5OP) and less Glu than wild-type plants, suggesting substantial metabolite flux though 5OP and that 5OP is a major contributor to Glu steady-state levels. In the ggt1-1/ggt4-1/oxp1-1 triple mutant with no GGT activity in any organs except young siliques, the 5OP concentration in leaves was not different from that in oxp1-1, suggesting that GGTs are not major contributors to 5OP production in Arabidopsis. 5OP formation strongly tracked the level of GSH in Arabidopsis plants, suggesting that GSH is the precursor of 5OP in a GGT-independent reaction. Kinetics analysis suggests that gamma-glutamyl cyclotransferase is the major source of GSH degradation and 5OP formation in Arabidopsis. This discovery led us to propose a new pathway for GSH turnover in plants where GSH is converted to 5OP and then to Glu by the combined action of gamma-glutamyl cyclotransferase and 5-oxoprolinase in the cytoplasm.

  4. Proteomic identification of Drosophila melanogaster male accessory gland proteins, including a pro-cathepsin and a soluble gamma-glutamyl transpeptidase.

    PubMed

    Walker, Michael J; Rylett, Caroline M; Keen, Jeff N; Audsley, Neil; Sajid, Mohammed; Shirras, Alan D; Isaac, R Elwyn

    2006-05-02

    In Drosophila melanogaster, the male seminal fluid contains proteins that are important for reproductive success. Many of these proteins are synthesised by the male accessory glands and are secreted into the accessory gland lumen, where they are stored until required. Previous studies on the identification of Drosophila accessory gland products have largely focused on characterisation of male-specific accessory gland cDNAs from D. melanogaster and, more recently, Drosophila simulans. In the present study, we have used a proteomics approach without any sex bias to identify proteins in D. melanogaster accessory gland secretions. Thirteen secreted accessory gland proteins, including seven new accessory gland proteins, were identified by 2D-gel electrophoresis combined with mass spectrometry of tryptic fragments. They included protein-folding and stress-response proteins, a hormone, a lipase, a serpin, a cysteine-rich protein and two peptidases, a pro-enzyme form of a cathepsin K-like cysteine peptidase and a gamma-glutamyl transpeptidase. Enzymatic studies established that accessory gland secretions contain a cysteine peptidase zymogen that can be activated at low pH. This peptidase may have a role in the processing of female and other male-derived proteins, but is unlikely to be involved in the processing of the sex peptide. gamma-Glutamyl transpeptidases are type II integral membrane proteins; however, the identified AG gamma-glutamyl transpeptidase (GGT-1) is unusual in that it is predicted to be a soluble secreted protein, a prediction that is supported by biochemical evidence. GGT-1 is possibly involved in maintaining a protective redox environment for sperm. The strong gamma-glutamyl transpeptidase activity found in the secretions provides an explanation for the observation that glutamic acid is the most abundant free amino acid in accessory gland secretions of D. melanogaster. We have applied biochemical approaches, not used previously, to characterise

  5. Structure of 6-diazo-5-oxo-norleucine-bound human gamma-glutamyl transpeptidase 1, a novel mechanism of inactivation.

    PubMed

    Terzyan, Simon S; Cook, Paul F; Heroux, Annie; Hanigan, Marie H

    2017-06-01

    Intense efforts are underway to identify inhibitors of the enzyme gamma-glutamyl transpeptidase 1 (GGT1) which cleaves extracellular gamma-glutamyl compounds and contributes to the pathology of asthma, reperfusion injury and cancer. The glutamate analog, 6-diazo-5-oxo-norleucine (DON), inhibits GGT1. DON also inhibits many essential glutamine metabolizing enzymes rendering it too toxic for use in the clinic as a GGT1 inhibitor. We investigated the molecular mechanism of human GGT1 (hGGT1) inhibition by DON to determine possible strategies for increasing its specificity for hGGT1. DON is an irreversible inhibitor of hGGT1. The second order rate constant of inactivation was 0.052 mM -1 min -1 and the K i was 2.7 ± 0.7 mM. The crystal structure of DON-inactivated hGGT1 contained a molecule of DON without the diazo-nitrogen atoms in the active site. The overall structure of the hGGT1-DON complex resembled the structure of the apo-enzyme; however, shifts were detected in the loop forming the oxyanion hole and elements of the main chain that form the entrance to the active site. The structure of hGGT1-DON complex revealed two covalent bonds between the enzyme and inhibitor which were part of a six membered ring. The ring included the OG atom of Thr381, the reactive nucleophile of hGGT1 and the α-amine of Thr381. The structure of DON-bound hGGT1 has led to the discovery of a new mechanism of inactivation by DON that differs from its inactivation of other glutamine metabolizing enzymes, and insight into the activation of the catalytic nucleophile that initiates the hGGT1 reaction. © 2017 The Protein Society.

  6. 21 CFR 862.1360 - Gamma-glutamyl transpeptidase and isoenzymes test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1360 Gamma-glutamyl transpeptidase and isoenzymes test system. (a...

  7. 21 CFR 862.1360 - Gamma-glutamyl transpeptidase and isoenzymes test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1360 Gamma-glutamyl transpeptidase and isoenzymes test system. (a...

  8. 21 CFR 862.1360 - Gamma-glutamyl transpeptidase and isoenzymes test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1360 Gamma-glutamyl transpeptidase and isoenzymes test system. (a... alcoholic cirrhosis and primary and secondary liver tumors. (b) Classification. Class I (general controls...

  9. "Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies".

    PubMed

    Verma, Ved Vrat; Gupta, Rani; Goel, Manisha

    2015-09-14

    γ-glutamyltranspeptidase (GGT) is a bi-substrate enzyme conserved in all three domains of life. It catalyzes the cleavage and transfer of γ-glutamyl moiety of glutathione to either water (hydrolysis) or substrates like peptides (transpeptidation). GGTs exhibit great variability in their enzyme kinetics although the mechanism of catalysis is conserved. Recently, GGT has been shown to be a virulence factor in microbes like Helicobacter pylori and Bacillus anthracis. In mammalian cells also, GGT inhibition prior to chemotherapy has been shown to sensitize tumors to the therapy. Therefore, lately both bacterial and eukaryotic GGTs have emerged as potential drug targets, but the efforts directed towards finding suitable inhibitors have not yielded any significant results yet. We propose that delineating the residues responsible for the functional diversity associated with these proteins could help in design of species/clade specific inhibitors. In the present study, we have carried out phylogenetic analysis on a set of 47 GGT-like proteins to address the functional diversity. These proteins segregate into various subfamilies, forming separate clades on the tree. Sequence conservation and motif prediction studies show that even though most of the highly conserved residues have been characterized biochemically in previous studies, a significant number of novel putative sites and motifs are discovered that vary in a clade specific manner. Many of the putative sites predicted during the functional divergence type I and type II analysis, lie close to the known catalytic residues and line the walls of the substrate binding cavity, reinforcing their role in modulating the substrate specificity, catalytic rates and stability of this protein. The study offers interesting insights into the evolution of GGT-like proteins in pathogenic vs. non-pathogenic bacteria, archaea and eukaryotes. Our analysis delineates residues that are highly specific to each GGT subfamily. We propose

  10. The Kinetics and Inhibition of Gamma-Glutamyl Transpeptidase: A Biochemistry Laboratory Experiment.

    ERIC Educational Resources Information Center

    Splittgerber, A. G.; Sohl, Julie

    1988-01-01

    Discusses an enzyme kinetics laboratory experiment involving a two substrate system for undergraduate biochemistry. Uses the enzyme gamma-glutamyl transpeptidase as this enzyme in blood serum is of clinical significance. Notes elevated levels are seen in liver disease, alcoholism, and epilepsy. Uses a spectrophotometer for the analysis. (MVL)

  11. Relationship between gamma-glutamyl transpeptidase activity and garlic greening, as controlled by temperature.

    PubMed

    Li, Lei; Hu, Dan; Jiang, Ying; Chen, Fang; Hu, Xiaosong; Zhao, Guanghua

    2008-02-13

    It was established that storage at low temperature (less than 10 degrees C) was required for garlic greening occurring either during processing or in the course of "Laba" garlic preparation while storage at high temperature (higher than 20 degrees C) inhibited its occurrence. However, the reason for this observation is unclear. To obtain insights into a tie connected between storage temperature and garlic greening, it was detected if the gamma-glutamyl transpeptidase (GGT) activity correlated with garlic greening because the activity of this enzyme is very sensitive to storage temperature. Results showed that garlic puree (which was prepared from fresh garlic) turned green upon addition of GGT but the color of garlic puree remained unchanged when either water or heat-treated GGT (which has no activity due to heat treatment) was used, a result giving a positive answer to the above proposal. Subsequently, to further clarify the relationship between the GGT activity and garlic greening, the GGT activity, the degree of garlic greening, and the concentration of total thiosulfinates in garlic bulbs were determined respectively after the garlic bulbs had been stored at 4 degrees C for up to 59 days followed by storage at 35 degrees C for up to 22 days. It was found that cold storage facilitated the GGT activity whereas warm storage inhibited the activity of this enzyme, just like the effect of storage temperature on greening, indicating that the increase of GGT activity could be a direct factor resulting in garlic greening. Consistent with this conclusion, the concentration of total thiosulfinates (the color developers) in garlic purees likewise exhibited a reversible change by moving garlic bulbs from one low storage temperature to a higher one; namely, it increased with increasing storage time during storage at 4 degrees C while decreasing as storage time increased during storage at 35 degrees C. The present study provided direct evidence that the GGT is involved in

  12. gamma-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver.

    PubMed

    Obrador, Elena; Carretero, Julian; Ortega, Angel; Medina, Ignacio; Rodilla, Vicente; Pellicer, José A; Estrela, José M

    2002-01-01

    B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and high metastatic activity in the liver in vivo. gamma-Glutamyl transpeptidase (GGT)-mediated extracellular GSH cleavage and intracellular GSH synthesis were studied in vitro in B16M cells with high (F10) and low (F1) metastatic potential. GGT activity was modified by transfection with the human GGT gene (B16MF1/Tet-GGT cells) or by acivicin-induced inhibition. B16MF1/Tet-GGT and B16MF10 cells exhibited higher GSH content (35 +/- 6 and 40 +/- 5 nmol/10(6) cells, respectively) and GGT activity (89 +/- 9 and 37 +/- 7 mU/10(6) cells, respectively) as compared (P <.05) with B16MF1 cells (10 +/- 3 nmol GSH and 4 mU GGT/10(6) cells). Metastasis (number of foci/100 mm(3) of liver) increased in B16MF1 cells pretreated with GSH ester ( approximately 3-fold, P <.01), and decreased in B16MF1/Tet-GGT and B16MF10 cells pretreated with the GSH synthesis inhibitor L-buthionine (S,R)-sulphoximine ( approximately 5-fold and 2-fold, respectively, P <.01). Liver, kidney, brain, lung, and erythrocyte GSH content in B16MF1/Tet-GGT- or B16MF10-bearing mice decreased as compared with B16MF1- and non-tumor-bearing mice. Organic anion transporting polypeptide 1-independent sinusoidal GSH efflux from hepatocytes increased in B16MF1/Tet-GGT- or B16MF10-bearing mice ( approximately 2-fold, P <.01) as compared with non-tumor-bearing mice. Our results indicate that tumor GGT activity and an intertissue flow of GSH can regulate GSH content of melanoma cells and their metastatic growth in the liver.

  13. Structure of 6-diazo-5-oxo-norleucine-bound human gamma-glutamyl transpeptidase 1, a novel mechanism of inactivation

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

    Terzyan, Simon S.; Cook, Paul F.; Heroux, Annie

    Intense efforts are underway to identify inhibitors of the enzyme gamma–glutamyl transpeptidase 1 (GGT1) which cleaves extracellular gamma–glutamyl compounds and contributes to the pathology of asthma, reperfusion injury and cancer. The glutamate analog, 6–diazo–5–oxo–norleucine (DON), inhibits GGT1. DON also inhibits many essential glutamine metabolizing enzymes rendering it too toxic for use in the clinic as a GGT1 inhibitor. We investigated the molecular mechanism of human GGT1 (hGGT1) inhibition by DON to determine possible strategies for increasing its specificity for hGGT1. DON is an irreversible inhibitor of hGGT1. The second order rate constant of inactivation was 0.052 m M –1 minmore » –1 and the K i was 2.7 ± 0.7 m M. The crystal structure of DON–inactivated hGGT1 contained a molecule of DON without the diazo–nitrogen atoms in the active site. The overall structure of the hGGT1–DON complex resembled the structure of the apo–enzyme; however, shifts were detected in the loop forming the oxyanion hole and elements of the main chain that form the entrance to the active site. The structure of hGGT1–DON complex revealed two covalent bonds between the enzyme and inhibitor which were part of a six membered ring. The ring included the OG atom of Thr381, the reactive nucleophile of hGGT1 and the α–amine of Thr381. As a result, the structure of DON–bound hGGT1 has led to the discovery of a new mechanism of inactivation by DON that differs from its inactivation of other glutamine metabolizing enzymes, and insight into the activation of the catalytic nucleophile that initiates the hGGT1 reaction.« less

  14. Structure of 6-diazo-5-oxo-norleucine-bound human gamma-glutamyl transpeptidase 1, a novel mechanism of inactivation

    DOE PAGES

    Terzyan, Simon S.; Cook, Paul F.; Heroux, Annie; ...

    2017-04-05

    Intense efforts are underway to identify inhibitors of the enzyme gamma–glutamyl transpeptidase 1 (GGT1) which cleaves extracellular gamma–glutamyl compounds and contributes to the pathology of asthma, reperfusion injury and cancer. The glutamate analog, 6–diazo–5–oxo–norleucine (DON), inhibits GGT1. DON also inhibits many essential glutamine metabolizing enzymes rendering it too toxic for use in the clinic as a GGT1 inhibitor. We investigated the molecular mechanism of human GGT1 (hGGT1) inhibition by DON to determine possible strategies for increasing its specificity for hGGT1. DON is an irreversible inhibitor of hGGT1. The second order rate constant of inactivation was 0.052 m M –1 minmore » –1 and the K i was 2.7 ± 0.7 m M. The crystal structure of DON–inactivated hGGT1 contained a molecule of DON without the diazo–nitrogen atoms in the active site. The overall structure of the hGGT1–DON complex resembled the structure of the apo–enzyme; however, shifts were detected in the loop forming the oxyanion hole and elements of the main chain that form the entrance to the active site. The structure of hGGT1–DON complex revealed two covalent bonds between the enzyme and inhibitor which were part of a six membered ring. The ring included the OG atom of Thr381, the reactive nucleophile of hGGT1 and the α–amine of Thr381. As a result, the structure of DON–bound hGGT1 has led to the discovery of a new mechanism of inactivation by DON that differs from its inactivation of other glutamine metabolizing enzymes, and insight into the activation of the catalytic nucleophile that initiates the hGGT1 reaction.« less

  15. γ-Glutamyl transpeptidase has a role in the persistent colonization of the avian gut by Campylobacter jejuni

    PubMed Central

    Barnes, If H.A.; Bagnall, Mary C.; Browning, Darren D.; Thompson, Stuart A.; Manning, Georgina; Newell, Diane G.

    2009-01-01

    The contribution of γ-glutamyl transpeptidase (GGT) to Campylobacter jejuni virulence and colonization of the avian gut has been investigated. The presence of the ggt gene in C. jejuni strains directly correlated with the expression of GGT activity as measured by cleavage and transfer of the γ-glutamyl moiety. Inactivation of the monocistronic ggt gene in C. jejuni strain 81116 resulted in isogenic mutants with undetectable GGT activity; nevertheless, these mutants grew normally in vitro. However, the mutants had increased motility, a 5.4-fold higher invasion efficiency into INT407 cells in vitro and increased resistance to hydrogen peroxide stress. Moreover, the apoptosis-inducing activity of the ggt mutant was significantly lower than that of the parental strain. In vivo studies showed that, although GGT activity was not required for initial colonization of 1-day-old chicks, the enzyme was required for persistant colonization of the avian gut. PMID:17600669

  16. Human γ-glutamyl transpeptidase 1: Structures of the free enzyme, inhibitor-bound tetrahedral transition states, and glutamate-bound enzyme reveal novel movement within the active site during catalysis [Human gamma-glutamyl transpeptidase: Inhibitor binding and movement within the active site

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

    Terzyan, Simon S.; Burgett, Anthony W. G.; Heroux, Annie

    γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within themore » active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. Lastly,tThese data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use.« less

  17. Human γ-glutamyl transpeptidase 1: Structures of the free enzyme, inhibitor-bound tetrahedral transition states, and glutamate-bound enzyme reveal novel movement within the active site during catalysis [Human gamma-glutamyl transpeptidase: Inhibitor binding and movement within the active site

    DOE PAGES

    Terzyan, Simon S.; Burgett, Anthony W. G.; Heroux, Annie; ...

    2015-05-26

    γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within themore » active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. Lastly,tThese data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use.« less

  18. gamma-Glutamyl amino acids. Transport and conversion to 5-oxoproline in the kidney

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

    Bridges, R.J.; Meister, A.

    1985-06-25

    Transport of gamma-glutamyl amino acids, a step in the proposed glutathione-gamma-glutamyl transpeptidase-mediated amino acid transport pathway, was examined in mouse kidney. The transport of gamma-glutamyl amino acids was demonstrated in vitro in studies on kidney slices. Transport was followed by measuring uptake of /sup 35/S after incubation of the slices in media containing gamma-glutamyl methionine (/sup 35/S)sulfone. The experimental complication associated with extracellular conversion of the gamma-glutamyl amino acid to amino acid and uptake of the latter by slices was overcome by using 5-oxoproline formation (catalyzed by intracellular gamma-glutamyl-cyclotransferase) as an indicator of gamma-glutamyl amino acid transport. This method wasmore » also successfully applied to studies on transport of gamma-glutamyl amino acids in vivo. Transport of gamma-glutamyl amino acids in vitro and in vivo is inhibited by several inhibitors of gamma-glutamyl transpeptidase and also by high extracellular levels of glutathione. This seems to explain urinary excretion of gamma-glutamylcystine by humans with gamma-glutamyl transpeptidase deficiency and by mice treated with inhibitors of this enzyme. Mice depleted of glutathione by treatment with buthionine sulfoximine (which inhibits glutathione synthesis) or by treatment with 2,6-dimethyl-2,5-heptadiene-4-one (which effectively interacts with tissue glutathione) exhibited significantly less transport of gamma-glutamyl amino acids than did untreated controls. The findings suggest that intracellular glutathione functions in transport of gamma-glutamyl amino acids. Evidence was also obtained for transport of gamma-glutamyl gamma-glutamylphenylalanine into kidney slices.« less

  19. Cloning and expression of γ-glutamyl transpeptidase and its relationship to greening in crushed garlic (Allium sativum) cloves.

    PubMed

    Cho, Jungeun; Park, Minkyu; Choi, Doil; Lee, Seung Koo

    2012-01-30

    Garlic greening occurs when garlic cloves are stored at low temperature, increasing 1-propenyl cysteine sulfoxide, which is induced by γ-glutamyl transpeptidase (GGT) activity. Although the metabolism of the γ-glutamyl peptide is important for the biosynthesis of green pigments in crushed garlic cloves, garlic GGT is poorly characterised. For the analysis of GGT at the gene level, the garlic GGT sequence was partially cloned using an onion GGT sequence. The relationship between garlic greening and related gene expressions, depending on storage condition, was investigated using reverse transcription polymerase chain reaction for garlic GGT and alliinase. Three storage conditions were set: A, storage at a constant temperature of 20 °C; B, storage at 20 °C for 3 months and then transfer to 0 °C for an additional 3 months; C, storage at 0 °C for 3 months and then transfer to 20 °C for an additional 3 months. GGT expression increased under storage condition B and decreased under storage condition C. However, alliinase expression was not affected by storage condition. Greening in crushed garlic cloves increases with increasing GGT expression at low temperature, while alliinase expression is not affected. Copyright © 2011 Society of Chemical Industry.

  20. A γ-Glutamyl Transpeptidase-Independent Pathway of Glutathione Catabolism to Glutamate via 5-Oxoproline in Arabidopsis1[W][OA

    PubMed Central

    Ohkama-Ohtsu, Naoko; Oikawa, Akira; Zhao, Ping; Xiang, Chengbin; Saito, Kazuki; Oliver, David J.

    2008-01-01

    The degradation pathway of glutathione (GSH) in plants is not well understood. In mammals, GSH is predominantly metabolized through the γ-glutamyl cycle, where GSH is degraded by the sequential reaction of γ-glutamyl transpeptidase (GGT), γ-glutamyl cyclotransferase, and 5-oxoprolinase to yield glutamate (Glu) and dipeptides that are subject to peptidase action. In this study, we examined if GSH is degraded through the same pathway in Arabidopsis (Arabidopsis thaliana) as occurs in mammals. In Arabidopsis, the oxoprolinase knockout mutants (oxp1-1 and oxp1-2) accumulate more 5-oxoproline (5OP) and less Glu than wild-type plants, suggesting substantial metabolite flux though 5OP and that 5OP is a major contributor to Glu steady-state levels. In the ggt1-1/ggt4-1/oxp1-1 triple mutant with no GGT activity in any organs except young siliques, the 5OP concentration in leaves was not different from that in oxp1-1, suggesting that GGTs are not major contributors to 5OP production in Arabidopsis. 5OP formation strongly tracked the level of GSH in Arabidopsis plants, suggesting that GSH is the precursor of 5OP in a GGT-independent reaction. Kinetics analysis suggests that γ-glutamyl cyclotransferase is the major source of GSH degradation and 5OP formation in Arabidopsis. This discovery led us to propose a new pathway for GSH turnover in plants where GSH is converted to 5OP and then to Glu by the combined action of γ-glutamyl cyclotransferase and 5-oxoprolinase in the cytoplasm. PMID:18768907

  1. Divergent effects of compounds on the hydrolysis and transpeptidation reactions of γ-glutamyl transpeptidase.

    PubMed

    Wickham, Stephanie; Regan, Nicholas; West, Matthew B; Kumar, Vidya Prasanna; Thai, Justin; Li, Pui Kai; Cook, Paul F; Hanigan, Marie H

    2012-08-01

    A novel class of inhibitors of the enzyme γ-glutamyl transpeptidase (GGT) were evaluated. The analog OU749 was shown previously to be an uncompetitive inhibitor of the GGT transpeptidation reaction. The data in this study show that it is an equally potent uncompetitive inhibitor of the hydrolysis reaction, the primary reaction catalyzed by GGT in vivo. A series of structural analogs of OU749 were evaluated. For many of the analogs, the potency of the inhibition differed between the hydrolysis and transpeptidation reactions, providing insight into the malleability of the active site of the enzyme. Analogs with electron withdrawing groups on the benzosulfonamide ring, accelerated the hydrolysis reaction, but inhibited the transpeptidation reaction by competing with a dipeptide acceptor. Several of the OU749 analogs inhibited the transpeptidation reaction by slow onset kinetics, similar to acivicin. Further development of inhibitors of the GGT hydrolysis reaction is necessary to provide new therapeutic compounds.

  2. Hyperproduction of γ-glutamyl transpeptidase from Bacillus licheniformis ER15 in the presence of high salt concentration.

    PubMed

    Bindal, Shruti; Gupta, Rani

    2017-02-07

    Microbial γ-glutamyl transpeptidases (GGTs) have been exploited in biotechnological, pharmaceutical, and food sectors for the synthesis of various γ-glutamyl compounds. But, till date, no bacterial GGTs are commercially available in the market because of lower levels of production from various sources. In the current study, production of GGT from Bacillus licheniformis ER15 was investigated to achieve high GGT titers. Hyperproduction of GGT from B. licheniformis ER15 was achieved with 6.4-fold enhancement (7921.2 ± 198.7 U/L) by optimization of culture medium following one-variable-at-a-time strategy and statistical approaches. Medium consisting of Na 2 HPO 4 : 0.32% (w/v); KH 2 PO 4 : 0.15% (w/v); starch: 0.1% (w/v); soybean meal: 0.5% (w/v); NaCl: 4.0% (w/v), and MgCl 2 : 5 mM was found to be optimal for maximum GGT titers. Maximum GGT titers were obtained, in the optimized medium at 37°C and 200 rpm, after 40 h. It was noteworthy that GGT production was a linear function of sodium chloride concentration, as observed during response surface methodology. While investigating the role of NaCl on GGT production, it was found that NaCl drastically decreased subtilisin concentration and indirectly increasing GGT recovery. B. licheniformis ER15 is proved to be a potential candidate for large-scale production of GGT enzyme and its commercialization.

  3. Amniotic fluid gamma-glutamyl transpeptidase activity during the second trimester.

    PubMed

    Legge, M; Potter, H C

    1986-03-12

    Gamma glutamyl transpeptidase (GGTP) activity was determined in second trimester amniotic fluid taken from normal fetuses and those with fetal abnormalities. GGTP activity decreased with advancing gestation. Increasing meconium contamination correlated with an increase in GGTP activity as did increasing fetal blood contamination. Maternal blood did not affect GGTP activity. Anencephaly did not significantly alter the GGTP activity, however, fetuses with spina bifida had significantly lower activity. Klinefelters and Turners syndromes both had GGTP activity close to the 50th percentile, and two trisomy 21 fetuses had GGTP activity below the 40th percentile. Two trisomy 18 fetuses and two translocation Downs syndromes (46 XY, t (14;21) had GGTP activities considerably lower than the 20th percentile as did a fetus with gastroschisis. Second trimester amniotic fluid GGTP activity may provide an easy preliminary test to screen amniotic fluids for the possibility of certain fetal chromosome abnormalities.

  4. Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

    PubMed

    Kim, Ha-Na; Kang, Sung-Goo; Roh, Yong Kyun; Choi, Min-Kyu; Song, Sang-Wook

    2017-08-01

    Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

  5. γ-glutamyl transpeptidase 1 specifically suppresses green-light avoidance via GABAA receptors in Drosophila.

    PubMed

    Liu, Jiangqu; Gong, Zhefeng; Liu, Li

    2014-08-01

    Drosophila larvae innately show light avoidance behavior. Compared with robust blue-light avoidance, larvae exhibit relatively weaker green-light responses. In our previous screening for genes involved in larval light avoidance, compared with control w(1118) larvae, larvae with γ-glutamyl transpeptidase 1 (Ggt-1) knockdown or Ggt-1 mutation were found to exhibit higher percentage of green-light avoidance which was mediated by Rhodopsin6 (Rh6) photoreceptors. However, their responses to blue light did not change significantly. By adjusting the expression level of Ggt-1 in different tissues, we found that Ggt-1 in malpighian tubules was both necessary and sufficient for green-light avoidance. Our results showed that glutamate levels were lower in Ggt-1 null mutants compared with controls. Feeding Ggt-1 null mutants glutamate can normalize green-light avoidance, indicating that high glutamate concentrations suppressed larval green-light avoidance. However, rather than directly, glutamate affected green-light avoidance indirectly through GABA, the level of which was also lower in Ggt-1 mutants compared with controls. Mutants in glutamate decarboxylase 1, which encodes GABA synthase, and knockdown lines of the GABAA receptor, both exhibit elevated levels of green-light avoidance. Thus, our results elucidate the neurobiological mechanisms mediating green-light avoidance, which was inhibited in wild-type larvae. © 2014 International Society for Neurochemistry.

  6. Gamma-glutamyl transpeptidase (GGT) blood test

    MedlinePlus

    ... test is used to detect diseases of the liver or bile ducts. It is also done with other tests (such ... and bilirubin tests) to tell the difference between liver or bile duct disorders and bone disease. It may also be ...

  7. The postoperative course of gamma-glutamyl transpeptidase--a marker of cytomegalovirus (CMV) replication risk?

    PubMed

    Schenk, M; Zipfel, A; Kratt, T; Petersen, P; Becker, H D; Viebahn, R

    2000-11-01

    Cytomegalovirus (CMV) infection is a common complication in the postoperative course of liver transplantation. In order to start early prophylactic therapy, but to avoid unnecessary treatment, or expensive screening, a desirable goal in post-transplant monitoring is to find appropriate markers in standard laboratory diagnostics. In the present study, the results of a 6-week CMV replication monitoring schedule by the pp65 antigenemia assay in 100 liver graft recipients were included. The activities of transaminases, glutamate dehydrogenase and gamma-glutamyl transpeptidase (gamma-GT) were measured by routine laboratory methods. In contrast to the transaminases, the serum activity of gamma-GT increased during the first postoperative week. The maximum levels were 246 +/- 211 U/l in patients without (n = 46) and 140 +/- 89 U/l in patients with early CMV replication (n = 54; p = 0.02). Patients with gamma-GT levels below 200 U/l on the 5th postoperative day (n = 72) had a CMV replication risk of 65%, whereas those patients with gamma-GT levels above this threshold had a risk of 30% (n = 28; p = 0.0007; relative risk = 2.9). These findings provide a routinely usable marker for the identification of patients at an increased risk of CMV replication. It can be considered that these phenomena may be caused by an additional immunosuppressive effect of the CMV virus.

  8. A role for gamma-glutamyl transpeptidase and the amino acid transport system xc- in cystine transport by a human pancreatic duct cell line.

    PubMed Central

    Sweiry, J H; Sastre, J; Viña, J; Elsässer, H P; Mann, G E

    1995-01-01

    1. The roles of the gamma-glutamyl cycle and the anionic amino acid transport system xc- in mediating L-cystine uptake were investigated in cultured human pancreatic duct PaTu 8902 cells. This cell line exhibits morphological features of normal pancreatic duct cells and expresses gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2), an enzyme involved in the metabolism and regulation of intracellular glutathione (GSH). 2. Uptake of L-cystine (10 microM) was linear for up to 10 min, temperature dependent, Na+ independent, saturable (Michaelis-Menten constant (Km), 86 +/- 25 microM; maximal velocity (Vmax), 109 +/- 33 nmol (mg protein)-1 h-1) and reduced by 80-90% by a 50-fold excess concentration of L-glutamate and L-homocysteic acid, but not L-aspartate. These transport properties resemble those described for system xc-, which exchanges cystine for intracellular glutamate. 3. Acivicin, a known inhibitor of gamma-GT, decreased gamma-GT activity from 2.58 +/- 0.96 to 0.97 +/- 0.11 mU (mg protein)-1 and decreased the initial rates of L-cystine and L-glutamine uptake by 41-55%. Anthglutin (1-gamma-L-glutamyl-2-(2-carboxyphenylhyl)hydrazine), a structurally different inhibitor of gamma-GT, also caused a concentration-dependent (0.01-1 mM) decrease in gamma-GT activity and L-cystine uptake. 4. Neither acivicin nor anthglutin inhibited the uptake of L-glutamate, a poor substrate for gamma-GT. 5. In the presence of a 500-fold excess concentration of glutamate, which should abolish entry of cystine via system xc-, the remaining fraction of cystine transport was inhibited by 50% by acivicin, suggesting that transport is, in part, dependent on the activity of gamma-GT. 6. Cystine transport was also 60-80% inhibited by a series of gamma-glutamyl amino acids (5 mM) including gamma-glutamyl-glutamate, gamma-glutamyl-glutamine and gamma-glutamyl-glycine. alpha-Dipeptides inhibited cystine transport by only 6-22%. 7. These findings demonstrate that in human pancreatic duct Pa

  9. Gamma-glutamyl transpeptidase to cholinesterase and platelet ratio in predicting significant liver fibrosis and cirrhosis of chronic hepatitis B.

    PubMed

    Liu, Danping; Li, Jian; Lu, Wei; Wang, Yanbing; Zhou, Xinlan; Huang, Dan; Li, Xiufen; Ding, Rongrong; Zhang, Zhanqing

    2018-06-12

    To evaluate the performance of a new mathematical model gamma- glutamyl transpeptidase to cholinesterase and platelet ratio (GCPR) versus gamma- glutamyl transpeptidase to platelet ratio (GPR) in predicting significant fibrosis and cirrhosis of chronic hepatitis B (CHB). A complete cohort of 2343 patients was divided into early and late cohort depending on the time of liver biopsy. With reference to the Scheuer standard, liver pathological stage ≥S2 and ≥S4 were defined as significant fibrosis and cirrhosis, respectively. ROC curve was used to evaluate the performance of investigated models. In early cohort,the areas under ROC curves (AUROCs) of GCPR in predicting significant fibrosis of HBeAg-positive and HBeAg-negative patients (0.782 and 0.775) were both significantly greater than those of GPR (0.748 and 0.747) (Z=8.198 and Z=6.023, both P<0.0001); the AUROCs of GCPR in predicting cirrhosis of HBeAg-positive and HBeAg-negative patients (0.842 and 0.861) were both significantly greater than those of GPR (0.802 and 0.823) (Z=6.686 and Z=6.116, both P<0.0001). In early, late and complete cohort, using a single cutoff of GPCR>0.080, the specificities of GCPR in predicting significant fibrosis of HBeAg-positive patients were 83.3%, 88.2% and 85.0%, and of HBeAg-negative patients were 87.6%, 87.4% and 87.6%, respectively; and the sensitivities of GCPR in predicting cirrhosis of HBeAg-positive patients were 81.9%, 88.7% and 84.2%, and of HBeAg-negative patients were 83.1%,82.1% and 82.7%, respectively. GCPR has higher performance than GPR in predicting significant fibrosis and cirrhosis of CHB. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Serum Gamma-Glutamyl-Transferase Independently Predicts Outcome After Transarterial Chemoembolization of Hepatocellular Carcinoma: External Validation

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

    Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Deschamps, Frederic; Boulin, Mathieu

    Purpose: An Asian study showed that gamma glutamyl transpeptidase (GGT) can predict survival after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). This study was designed to validate in a European population this biomarker as an independent predictor of outcome after TACE of HCC and to determine a threshold value for clinical use. Methods: In 88 consecutive patients treated by TACE for HCC, the optimal threshold for GGT serum level was determined by a ROC analysis. Endpoints were time-to-treatment failure (TTTF) and overall survival (OS). All multivariate models were internally validated using bootstrapping (90 replications). Results: Median follow-up lasted 373 days,more » and median overall survival was 748 days. The optimal threshold for GGT was 165 U/L (sensitivity: 89.3%; specificity: 56.7%; area under the ROC curve: 0.7515). Median TTTF was shorter when GGT was {>=}165 U/L (281 days vs. 850 days; P < 0.001). GGT {>=}165 U/L (hazard ratio (HR) = 2.06; P = 0.02), WHO PS of 2 (HR = 5.4; P = 0.002), and tumor size (HR = 1.12; P = 0.014) were independently associated with shorter TTTF. Median OS was shorter when GGT was {>=}165 U/L (508 days vs. not reached; P < 0.001). GGT {>=} 165 U/L (HR = 3.05; P = 0.029), WHO PS of 2 (HR = 12.95; P < 0.001), alfa-fetoprotein (HR = 2.9; P = 0.01), and tumor size (HR = 1.096; P = 0.013) were independently associated with shorter OS. The results were confirmed by bootstrapping. Conclusions: Our results provide in a European population the external validation of GGT as an independent predictor of outcome after TACE of HCC. A serum level of GGT {>=} 165 U/L is independently associated with both shorter TTTF and OS.« less

  11. Human γ-Glutamyl Transpeptidase 1: STRUCTURES OF THE FREE ENZYME, INHIBITOR-BOUND TETRAHEDRAL TRANSITION STATES, AND GLUTAMATE-BOUND ENZYME REVEAL NOVEL MOVEMENT WITHIN THE ACTIVE SITE DURING CATALYSIS.

    PubMed

    Terzyan, Simon S; Burgett, Anthony W G; Heroux, Annie; Smith, Clyde A; Mooers, Blaine H M; Hanigan, Marie H

    2015-07-10

    γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within the active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. These data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Is gamma-glutamyl transpeptidase a biomarker for oxidative stress in periodontitis?

    PubMed Central

    Sreeram, Meenakshi; Suryakar, Adinath Narayan; Dani, Nitin Hemchandra

    2015-01-01

    Context: Periodontal disease and oxidative stress (OS) are part of a vicious cycle with each causing a deleterious effect on the other causing changes in the levels of antioxidants, and enzymes of antioxidant defense. Biomarkers and methods used for measuring OS are very expensive. Aims: To see how gamma-glutamyltransferase (GGT) fares, as a biomarker for OS in periodontits along with other routinely used biomarkers. Design: A cross-sectional study involving 300 people of which 150 were cases and 150 were controls. Setting: Candidates enrolled were patients visiting the OPD of MGV's Dental College and Hospital, Nasik, India between January 2011 and December 2012. Materials and Methods: Serum samples of patients with periodontitis, and controls were analyzed for malondialdehyde, superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid, and GGT. Statistical Analysis Used: Analysis was performed using Student's t test. P <0.05 were considered to be significant. Results: Malondialdehyde values were found to be significantly higher cases, while SOD, GPx and uric acid levels were found to be lower than controls. GGT levels were significantly higher in cases as compared to controls. Conclusions: GGT may be used as a cheap, quick, easy and precise marker for measuring OS. PMID:26015663

  13. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa.

    PubMed

    Lemoine, Maud; Shimakawa, Yusuke; Nayagam, Shevanthi; Khalil, Mustapha; Suso, Penda; Lloyd, Jo; Goldin, Robert; Njai, Harr-Freeya; Ndow, Gibril; Taal, Makie; Cooke, Graham; D'Alessandro, Umberto; Vray, Muriel; Mbaye, Papa Saliou; Njie, Ramou; Mallet, Vincent; Thursz, Mark

    2016-08-01

    Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa. Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets). Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4. The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Isolation and Identification of Three γ-Glutamyl Tripeptides and Their Putative Production Mechanism in Aged Garlic Extract.

    PubMed

    Nakamoto, Masashi; Fujii, Takuto; Matsutomo, Toshiaki; Kodera, Yukihiro

    2018-03-21

    We analyzed aged garlic extract (AGE) to understand its complex sulfur chemistry using post-column high-performance liquid chromatography with an iodoplatinate reagent and liquid chromatography high resolution mass spectrometry (LC-MS). We observed unidentified peaks of putative sulfur compounds. Three compounds were isolated and identified as γ-glutamyl-γ-glutamyl- S-methylcysteine, γ-glutamyl-γ-glutamyl- S-allylcysteine (GGSAC) and γ-glutamyl-γ-glutamyl- S-1-propenyl-cysteine (GGS1PC) by nuclear magnetic resonance and LC-MS analysis based on comparisons with chemically synthesized reference compounds. GGSAC and GGS1PC were novel compounds. Trace amounts of these compounds were detected in raw garlic, but the contents of these compounds increased during the aging process. Production of these compounds was inhibited using a γ-glutamyl transpeptidase (GGT) inhibitor in the model reaction mixtures. These findings suggest that γ-glutamyl tripeptides in AGE are produced by GGT during the aging process.

  15. Expression optimization and biochemical characterization of a recombinant gamma-glutamyltranspeptidase from Escherichia coli novablue.

    PubMed

    Yao, Ya-Feng; Weng, Yih-Ming; Hu, Hui-Yu; Ku, Kuo-Lung; Lin, Long-Liu

    2006-09-01

    A truncated Escherichia coli Novablue gamma-glutamyltranspeptidase (EcGGT) gene lacking the first 48-bp coding sequence for part of the signal sequence was amplified by polymerase chain reaction and cloned into expression vector pQE-30 to generate pQE-EcGGT. The maximum production of His(6)-tagged enzyme by E. coli M15 (pQE-EcGGT) was achieved with 0.1 mM IPTG induction for 12 h at 20 degrees C. The overexpressed enzyme was purified to homogeneity by nickel-chelate chromatography to a specific transpeptidase activity of 4.25 U/mg protein and a final yield of 83%. The molecular masses of the subunits of the purified enzyme were estimated to be 41 and 21 kDa respectively by SDS-PAGE, indicating EcGGT still undergoes the post-translational cleavage even in the truncation of signal sequence. The optimum temperature and pH for the recombinant enzyme were 40 degrees C and 9, respectively. The apparent K (m) and V (max) values for gamma-glutamyl-p-nitroanilide as gamma-glutamyl donor in the transpeptidation reaction were 37.9 microM and 53.7 x 10(-3) mM min(-1), respectively. The synthesis of L -theanine was performed in a reaction mixture containing 10 mM L -Gln, 40 mM ethylamine, and 1.04 U His(6)-tagged EcGGT/ml, pH 10, and a conversion rate of 45% was obtained.

  16. Gamma glutamyl transferase is an independent determinant for the association of insulin resistance with nonalcoholic fatty liver disease in Bangladeshi adults: Association of GGT and HOMA-IR with NAFLD.

    PubMed

    Hossain, Israt Ara; Rahman Shah, Md Mijanur; Rahman, Mohammad Khalilur; Ali, Liaquat

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with insulin resistance (HOMA-IR) syndrome. Recently serum gamma glutamyl transferase (GGT) has been considered as surrogate marker of NAFLD leading to oxidative stress and hepatocellular damage. In the present study we examined the association of serum GGT and HOMA-IR with NAFLD in Bangladeshi adult subjects. Under a cross-sectional analytical design a total of 110 subjects were recruited who came for their routine health check up in the BIHS Hospital, Darussalam, Dhaka, Bangladesh. After whole abdomen ultrasonography, 62 were diagnosed as non-NAFLD and 48 were NAFLD subjects. Serum glucose was measured by glucose-oxidase method, lipid profile and liver enzymes by enzymatic colorimetric method, glycosylated hemoglobin (HbA1c) was measured by high performance liquid chromatography (HPLC), serum insulin were measured by enzyme-linked immunosorbent assay. HOMA-IR was calculated by homeostasis model assessment (HOMA). NAFLD subjects had significantly higher levels of GGT and HOMA-IR as compared to their non-NAFLD counterparts. Multiple linear regression analysis showed a significant positive association of HOMA-IR with GGT after adjusting the effects of waist circumference (WC) and HbA1c. In binary logistic regression analysis, HOMA-IR and GGT were found to be significant determinants of NAFLD after adjusting the effects of WC and HbA1c. These results suggest that elevated levels of GGT and insulin resistance are more likely to develop NAFLD and thus support a role of these determinants in the pathogenesis of NAFLD in Bangladeshi adult subjects. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  17. Synthesis and evaluation of the inhibitory activity of the four stereoisomers of the potent and selective human γ-glutamyl transpeptidase inhibitor GGsTop.

    PubMed

    Watanabe, Bunta; Tabuchi, Yukiko; Wada, Kei; Hiratake, Jun

    2017-11-01

    2-Amino-4-{[3-(carboxymethyl)phenoxy](methoxy)phosphoryl}butanoic acid (GGsTop) is a potent, highly selective, nontoxic, and irreversible inhibitor of γ-glutamyl transpeptidase (GGT). GGsTop has been widely used in academic and medicinal research, and also as an active ingredient (Nahlsgen) in commercial anti-aging cosmetics. GGsTop consists of four stereoisomers due to the presence of two stereogenic centers, i.e., the α-carbon atom of the glutamate mimic (l/d) and the phosphorus atom (R P /S P ). In this study, each stereoisomer of GGsTop was synthesized stereoselectively and their inhibitory activity against human GGT was evaluated. The l- and d-configurations of each stereoisomer were determined by a combination of a chiral pool synthesis and chiral HPLC analysis. The synthesis of the four stereoisomers of GGsTop used chiral synthetic precursors that were separated by chiral HPLC on a preparative scale. With respect to the configuration of the α-carbon atom of the glutamate mimic, the l-isomer (k on =174M -1 s -1 ) was ca. 8-fold more potent than the d-isomer (k on =21.5M -1 s -1 ). In contrast, the configuration of the phosphorus atom is critical for GGT inhibitory activity. Based on a molecular modeling approach, the absolute configuration of the phosphorus atom of the active GGsTop isomers was postulated to be S P . The S P -isomers inhibited human GGT (k on =21.5-174M -1 s -1 ), while the R P -isomers were inactive even at concentrations of 0.1mM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians.

    PubMed

    Haren, Matthew T; Li, Ming; Petkov, John; McDermott, Robyn A

    2010-08-03

    The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians. Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (>or=50 U/L) were analyzed using logistic regression. Overall, 26% of the population had GGT>or=50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 - 8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]). In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT.

  19. Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians

    PubMed Central

    2010-01-01

    Background The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians. Methods Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (≥50 U/L) were analyzed using logistic regression. Results Overall, 26% of the population had GGT≥50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 - 8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]). Conclusions In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT. PMID:20682033

  20. Gamma glutamyl transferase and oxidative stress in obstructive sleep apnea: a study in 1744 patients.

    PubMed

    Sánchez-Armengol, A; Villalobos-López, P; Caballero-Eraso, C; Carmona-Bernal, C; Asensio-Cruz, M; Barbé, F; Capote, F

    2015-09-01

    We analyze a large population of patients to determine whether gamma glutamyl transferase (GGT) levels are increased in sleep apnea-hypopnea syndrome (OSA) and whether these levels are related to clinical characteristics or polygraphic indexes. A cross-sectional study in a population of 1744 patients referred for OSA suspicion was conducted. The following variables were determined: glucose, cholesterol, triglycerides, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), GGT, body mass index, waist-hip ratio (WHR), and overnight sleep study. The 483 patients with GGT ≥40 IU/l were younger and more obese, and had a pattern of more centrally distributed fat than the 1261 with GGT <40 IU/l. Patients with high levels of GGT also consumed more alcohol, had a poorer biochemical profile, and had more respiratory and oximetric alterations during sleep. GGT levels were significantly correlated with AHI, DI, and CT90. In the binary regression test, WHR, glucose, cholesterol, triglycerides, and grams of alcohol consumed per day predicted GGT levels ≥40 IU/l, while none of the polygraphic variables had predictive value. High GGT levels were associated with the severity of OSA. However, this relationship seems to be due to the coexistence of other associated factors, mainly central obesity, rather than to the respiratory disorders found in this disease.

  1. Oxidative Stress as Estimated by Gamma-Glutamyl Transferase Levels Amplifies the Alkaline Phosphatase-Dependent Risk for Mortality in ESKD Patients on Dialysis

    PubMed Central

    Mattace-Raso, Francesco; van Saase, Jan L. C. M.; Postorino, Maurizio; Tripepi, Giovanni Luigi; Mallamaci, Francesca; PROGREDIRE Study Group

    2016-01-01

    Alkaline phosphatase (Alk-Phos) is a powerful predictor of death in patients with end-stage kidney disease (ESKD) and oxidative stress is a strong inducer of Alk-Phos in various tissues. We tested the hypothesis that oxidative stress, as estimated by a robust marker of systemic oxidative stress like γ-Glutamyl-Transpeptidase (GGT) levels, may interact with Alk-Phos in the high risk of death in a cohort of 993 ESKD patients maintained on chronic dialysis. In fully adjusted analyses the HR for mortality associated with Alk-Phos (50 IU/L increase) was progressively higher across GGT quintiles, being minimal in patients in the first quintile (HR: 0.89, 95% CI: 0.77–1.03) and highest in the GGT fifth quintile (HR: 1.13, 95% CI: 1.03–1.2) (P for the effect modification = 0.02). These findings were fully confirmed in sensitivity analyses excluding patients with preexisting liver disease, excessive alcohol intake, or altered liver disease biomarkers. GGT amplifies the risk of death associated with high Alk-Phos levels in ESKD patients. This observation is compatible with the hypothesis that oxidative stress is a strong modifier of the adverse biological effects of high Alk-Phos in this population. PMID:27525053

  2. Probing the Donor and Acceptor Substrate Specificity of the Gamma-Glutamyl Transpeptidase

    DTIC Science & Technology

    2012-01-17

    glutathione can function as a source of cysteine. Mutant strains of F. tularensis that lack functional GGT have been shown to have impaired intracellular...conservation of structure and function between human and bacterial GGT homologues, significant differences in acceptor substrate and inhibitor preferences are...with the lowest value of MODELER objective function . The three-dimensional (3D) fold of the generated models was verified with PROSA II,40 and

  3. Association between gamma glutamyl transferase and insulin resistance markers in healthy obese children.

    PubMed

    Kaushik, Girdhar Gopal; Sharm, Sonali; Sharma, Reenu; Mittal, Prerna

    2009-10-01

    To study the relationship of gamma glutamyl transferase (GGT) with insulin resistance markers [fasting insulin and Homeostasis Model Assessment of-insulin resistance (HOMA-IR)] and to assess the role of GGT as a determinant of insulin resistance in healthy obese children. Fifty healthy obese children (boys and girls with mean age 9.2 +/- 0.73 and 8.8 +/- 0.74 years) born to diabetic mothers were studied. In all the subjects, anthropometric measurements viz, BMI and body weight were studied. The biochemical parameters analysed in fasting samples of subjects were plasma glucose, plasma insulin, serum GGT and calculation of HOMA-IR. The fifty studied subjects belonged to age group 8 to12 years. The difference in mean age of boys and girls was not significant (p = 0.09). Body weight values in all subjects ranged from 20 to 78 kgs and BMI values ranged from 14.5 to 42.1 Kg/m2. No significant difference was observed between body weight and BMI values when compared between boys and girls. A similar trend was observed in the values of biochemical parameters viz, fasting glucose, fasting insulin and HOMA-IR levels when compared between boys and girls (p = 0.72, p = 0.80, p = 0.59). Serum GGT correlated significantly with age, body weight, BMI, fasting insulin and HOMA-IR levels. HOMA-IR values also showed significant correlation with body weight, BMI, fasting glucose and fasting insulin levels. The association of GGT with fasting insulin and HOMA-IR levels was considerably significant compared to its association with other variables. The serum activity of GGT remained correlated with HOMA-IR even after removing the effect of BMI, weight and age on GGT values. The results showed that GGT is a determinant of HOMA-IR independently of age, BMI and weight. A correlation exists between GGT and insulin resistance markers. The observed correlation indicates that monitoring GGT and fasting insulin levels in obese children might serve to help prevent the development of diabetes in

  4. Are serum gamma-glutamyl transferase, high-sensitivity C-reactive protein, and ischaemia-modified albumin useful in diagnosing PCOS?

    PubMed

    Ozturk, Mustafa; Keskin, Ugur; Ozturk, Ozlem; Ulubay, Mustafa; Alanbay, İbrahim; Aydin, Aytekin; Yenen, Müfit Cemal

    2016-10-01

    We assessed the serum levels of gamma-glutamyl transferase (GGT), high-sensitivity C-reactive protein (hsCRP) and ischaemia-modified albumin (IMA) in patients with polycystic ovary syndrome (PCOS). Fifty-three patients with PCOS were included in our study along with 40 women with no PCOS as the control group. The patients were divided according to their body mass index (BMI). GGT levels were significantly higher in the women with PCOS than the women in the control group (p < 0.05). They were also significantly higher in the PCOS women who were normoweight and overweight than the normoweight and overweight women in the control group (p < 0.001). There was no significant difference in the circulating levels of hsCRP and IMA between the women with PCOS and the controls or between the normoweight and overweight subgroups. GGT may be associated with the diagnosis of PCOS when the threshold is set at >15.5 U/L. With the application of this threshold, raised GGT levels had 83% sensitivity (95% CI 0.70-0.90) and 67.5% specificity (95% CI 0.52-0.79), for the diagnosis of PCOS. In our study, GGT levels were elevated in the PCOS patients independent of BMI and could thus be an important marker of PCOS.

  5. Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China.

    PubMed

    Huang, Rui; Wang, Guiyang; Tian, Chen; Liu, Yong; Jia, Bei; Wang, Jian; Yang, Yue; Li, Yang; Sun, Zhenhua; Yan, Xiaomin; Xia, Juan; Xiong, Yali; Song, Peixin; Zhang, Zhaoping; Ding, Weimao; Wu, Chao

    2017-08-17

    The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

  6. Hair mercury association with selenium, serum lipid spectrum, and gamma-glutamyl transferase activity in adults.

    PubMed

    Tinkov, Alexey A; Skalnaya, Margarita G; Demidov, Vasily A; Serebryansky, Eugeny P; Nikonorov, Alexandr A; Skalny, Anatoly V

    2014-12-01

    The primary objective of the research is to estimate the dependence between hair mercury content, hair selenium, mercury-to-selenium ratio, serum lipid spectrum, and gamma-glutamyl transferase (GGT) activity in 63 adults (40 men and 23 women). Serum triglyceride (TG) concentration in the high-mercury group significantly exceeded the values obtained for low- and medium-mercury groups by 72 and 42 %, respectively. Serum GGT activity in the examinees from high-Hg group significantly exceeded the values of the first and the second groups by 75 and 28 %, respectively. Statistical analysis of the male sample revealed similar dependences. Surprisingly, no significant changes in the parameters analyzed were detected in the female sample. In all analyzed samples, hair mercury was not associated with hair selenium concentrations. Significant correlation between hair mercury content and serum TG concentration (r = 0.531) and GGT activity (r = 0.524) in the general sample of the examinees was detected. The respective correlations were observed in the male sample. Hair mercury-to-selenium ratios significantly correlated with body weight (r = 0.310), body mass index (r = 0.250), serum TG (r = 0.389), atherogenic index (r = 0.257), and GGT activity (r = 0.393). The same correlations were observed in the male sample. Hg/Se ratio in women did not correlate with the analyzed parameters. Generally, the results of the current study show the following: (1) hair mercury is associated with serum TG concentration and GGT activity in men, (2) hair selenium content is not related to hair mercury concentration, and (3) mercury-to-selenium ratio correlates with lipid spectrum parameters and GGT activity.

  7. Enzymes of the γ-Glutamyl Cycle in the Ciliary Body and Lens

    PubMed Central

    Ross, Leonard L.; Barber, Lee; Tate, Suresh S.; Meister, Alton

    1973-01-01

    The enzymes of the γ-glutamyl cycle have been found in rabbit ciliary body and, except for 5-oxoprolinase, also in the ocular lens. Histochemical studies show that γ-glutamyl transpeptidase is localized mainly in the basal portions of the epithelial cells of the ciliary body; the findings are similar to those observed in the chloroid plexuses. The histochemical staining reaction in the ciliary epithelium is more intense than in the chloroid plexus, intestine, and kidney. γ-Glutamyl transpeptidase staining activity in the epithelium of the intestinal and renal proximal convoluted tubules is confined to the microvillus border. Moderate transpeptidase activity was found in the cytoplasm of nonpigmented epithelial cells of the iris at the posterior pupillary margin. The histochemical and enzyme activity studies are consistent with the thesis that the γ-glutamyl cycle functions in transport of amino acids across the blood-aqueous humor barrier. Images PMID:4152058

  8. Use of urinary γ-glutamyl transferase (GGT) to monitor the pattern of proteinuria in dogs with leishmaniasis treated with N-methylglucamine antimoniate.

    PubMed

    Paltrinieri, Saverio; Mangiagalli, Giulia; Ibba, Fabrizio

    2018-05-25

    The aim of this study was to assess if the coupled analysis of the urinary protein to creatinine (UPC) ratio and of the GGT/UC ratio (the ratio between urinary γ-glutamyl transferase activity and urinary creatinine) may be used in treated leishmaniotic dogs to differentiate dogs with transient impairment of tubular function from dogs with persistent tubular damage. To this aim, 40 urine from 10 proteinuric and leishmaniotic dogs that at the first visit had high GGT/UC ratio, consistent with tubular damage, were collected and analyzed before treatments and 2, 4 and 6 weeks after treatment with N-methylglucamine antimoniate and allopurinol. Compared with pre-treatment values, at the end of the study period the UPC ratio decreased only in 5/10 dogs, which, however, were still proteinuric or borderline proteinuric. Conversely, the GGT/CU ratio decreased in 8/10 dogs and in 3 of them the values at the end of the study period were below the threshold consistent with tubular proteinuria. The GGT/UC values at 6 weeks was significantly lower than before treatment. However, transient increases were frequent for both the analytes. These results indicate that in most of the dogs that remain proteinuric after treatment, likely due to the persistent glomerular damage, the GGT/UC ratio tends to normalize. This suggests that in these dogs tubular proteinuria at admission depends on functional impairment of tubular cells likely due to the overflow of proteins from damaged glomeruli. However, tubular proteinuria occasionally persists, suggesting that tubulointerstitial damages persist even in dogs responsive to treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. The use of iohexol in pediatric urography: a comparative study with meglumine diatrizoate.

    PubMed

    Bani, E; Federighi, F; Ghio, R; Marchitiello, M; Galigani, P; Palla, R

    1985-01-01

    In a prospective study the nephrotoxicity of iohexol, a new non-ionic contrast medium, was compared with meglumine diatrizoate. Plasma creatinine, BUN, creatinine clearance, urinalysis and the urinary excretion of N-acetyl glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and muramidase (MU) were determined prior to and following intravenous pyelography. A significant rise in the enzyme excretion was observed in patients who received iohexol and diatrizoate. Statistical analysis failed to demonstrate any difference in nephrotoxicity between the two iodinated contrast media.

  10. Escherichia coli K-12 can utilize an exogenous gamma-glutamyl peptide as an amino acid source, for which gamma-glutamyltranspeptidase is essential.

    PubMed

    Suzuki, H; Hashimoto, W; Kumagai, H

    1993-09-01

    Escherichia coli K-12 can utilize a gamma-glutamyl peptide as an amino acid source, for which gamma-glutamyltranspeptidase (EC 2.3.2.2) is essential. We suggest that the gamma-glutamyl linkage of a gamma-glutamyl peptide is hydrolyzed by gamma-glutamyltranspeptidase located in the periplasmic space, and the released amino acid is taken up and utilized by E. coli.

  11. Serum gamma-glutamyl transferase activity is an independent predictor for cardiovascular disease in obstructive sleep apnea syndrome.

    PubMed

    Kanbay, Asiye; Kaya, Elif; Buyukoglan, Hakan; Ozdogan, Nezihe; Kaya, Mehmet Gungor; Oymak, Fatma Sema; Gulmez, Inci; Demir, Ramazan; Kokturk, Oguz

    2011-04-01

    Gamma glutamyl transferase (GGT) is a new marker for predicting myocardial infarction, stroke, cardiac death and inflammation. There is also a strong relationship between Obstructive Sleep Apnea Syndrome (OSAS) and cardiovascular disease. This study was designed to investigate the association between serum GGT levels and cardiovascular disease in patients with OSAS, and relationship between severity of OSAS and serum GGT level. We evaluated the medical records of 166 subjects who were admitted for sleep study. OSAS was diagnosed by polysomnography if Apnea-Hypopnea Index (AHI) > 5. According to AHI, individuals in whom AHI< 5 were recruited as group 1 (OSAS negative group), AHI = 5-15: group 2 (mild OSAS group), AHI = 15-30: group 3 (moderate OSAS group), AHI >30: group 4 (severe OSAS group). Cardiovascular disease was defined if the patients had heart failure, coronary artery disease or arrhythmia. Of the subjects, 112 (67.5%) were male and the mean age was 54.3 ± 12.2 years. There were 22 patients (13.2%), 17 patients (10.2%), 34 patients (20.4%) and 93 patients (56.2%) in group 1, 2, 3 and 4, respectively. There is a significant increase in serum GGT levels while AHI score increases (group 1 = 28.0 ± 10.1, group 2 = 33.8 ± 13.2, group 3 = 35.2 ± 8.5, group 4 = 40.0 ± 22.0; p for trend = 0.024). However, serum C-reactive protein (CRP), alanine aminotransferase and aspartate aminotransferase levels were similar in all groups (p > 0.05). There was a significant independent association between serum GGT levels and the severity of OSAS. Moreover, serum GGT levels were significantly high in patients with cardiovascular disease compared with patients without cardiovascular disease in severe-moderate-mild OSAS (p < 0.05) and OSAS negative groups while CRP levels were not. This was a significant independent association. The present study suggests that high serum GGT level, regardless of the other traditional risk factors, is an independent predictor of

  12. Clinical utility of urine kidney injury molecule-1 (KIM-1) and gamma-glutamyl transferase (GGT) in the diagnosis of canine acute kidney injury.

    PubMed

    Lippi, Ilaria; Perondi, F; Meucci, V; Bruno, B; Gazzano, V; Guidi, G

    2018-06-01

    The aim of the present study was to evaluate the sensitivity and specificity of urine KIM-1 and urine GGT for the detection of naturally-occurring AKI, compared to healthy control dogs, dogs with stable chronic kidney disease (CKD), and dogs with lower urinary tract disorders (LUTD). The study included AKI grade 1 (n = 21), AKI grade 2 to 5 (n = 11), stable CKD (n = 11), LUTD (n = 15), and healthy dogs (n = 37). Urine KIM-1 (ng/mg) and GGT (U/l) were normalized to urine creatinine (uCr). Statistically significant difference in KIM/uCr (p = 0.0007) and GGT/uCr (p < 0.0001) was found among the study groups. Area under the curve (AUC) for KIM-1/uCr and GGT/uCr as predictors of AKI was 0.81 and 0.91 respectively. Values of KIM-1/uCr of 0.73 ng/mg and of GGT/uCr of 54.33 showed the best combination of sensitivity and specificity (75% and 75.6%; 85.7% and 89.1% respectively). A significant positive correlation (p < 0.0001) between KIM-1/uCr and GGT/uCr was found. Both urine KIM-1/uCr and GGT/uCr seemed to be potentially good markers for the diagnosis of AKI. Dogs with AKI showed significantly higher levels of urine KIM-1/uCr and urine GGT/uCr, compared with healthy dogs. Caution should be used in the evaluation of elevated urine KIM-1/uCr and GGT/uCr in dogs with pre-existing CKD and/or LUTD. Urine KIM-1/uCr and GGT/uCr might have a significant clinical utility, as complementary test, particularly in diagnosis early, non-azotemic stages of AKI.

  13. GGT (Gamma-Glutamyl Transferase) Test

    MedlinePlus

    ... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

  14. Study of enzyme activities in the descending part of the duodenum in patients of duodenal ulcer.

    PubMed

    Fernandes, V L C; Bhasin, D K; Rana, S V

    2006-03-01

    The aim of this study was to measure the levels of lactase, sucrase, maltase, leucine amino peptidase and gamma-glutamyl transpeptidase in duodenum of Indian patients with duodenal ulcer. The effect of duodenum inflammation on these brush border enzymes has also been analysed in this study. Levels of lactase, sucrase, maltase, leucine amino peptidase and gamma-glutamyl transpeptidase were assessed in duodenal biopsies of 20 patients of duodenal ulcer and 20 non-ulcer dyspepsia. The duodenal biopsy specimens were also examined histopathologically for presence or absence of inflammation. There was no significant difference (p>0.05) in the activity of above mentioned enzyme levels in both the groups. Only levels of gamma-glutamyl transpeptidase were significantly decreased in patients of duodenal ulcer with duodenal inflammation. This study shows that only the levels of gamma-glutamyl transpeptidase were significantly decreased in patients of duodenal ulcer with inflammation but no change in duodenal enzymes due to duodenal ulcer as compared to non-ulcer dyspepsia.

  15. Preclinical Evaluation of a Potential GSH Ester Based PET/SPECT Imaging Probe DT(GSHMe)₂ to Detect Gamma Glutamyl Transferase Over Expressing Tumors.

    PubMed

    Khurana, Harleen; Meena, Virendra Kumar; Prakash, Surbhi; Chuttani, Krishna; Chadha, Nidhi; Jaswal, Ambika; Dhawan, Devinder Kumar; Mishra, Anil Kumar; Hazari, Puja Panwar

    2015-01-01

    Gamma Glutamyl Transferase (GGT) is an important biomarker in malignant cancers. The redox processes ensuing from GGT-mediated metabolism of extracellular GSH are implicated in critical aspects of tumor cell biology. Reportedly, Glutathione monoethyl ester (GSHMe) is a substrate of GGT, which has been used for its rapid transport over glutathione. Exploring GGT to be an important target, a homobivalent peptide system, DT(GSHMe)2 was designed to target GGT-over expressing tumors for diagnostic purposes. DT(GSHMe)2 was synthesized, characterized and preclinically evaluated in vitro using toxicity, cell binding assays and time dependent experiments. Stable and defined radiochemistry with 99mTc and 68Ga was optimized for high radiochemical yield. In vivo biodistribution studies were conducted for different time points along with scintigraphic studies of radiolabeled DT(GSHMe)2 on xenografted tumor models. For further validation, in silico docking studies were performed on GGT (hGGT1, P19440). Preclinical in vitro evaluations on cell lines suggested minimal toxicity of DT(GSHMe)2 at 100 μM concentration. Kinetic analysis revealed transport of 99mTc-DT(GSHMe)2 occurs via a saturable high-affinity carrier with Michaelis constant (Km) of 2.25 μM and maximal transport rate velocity (Vmax) of 0.478 μM/min. Quantitative estimation of GGT expression from western blot experiments showed substantial expression with 41.6 ± 7.07 % IDV for tumor. Small animal micro PET (Positron Emission Tomography)/CT(Computed Tomography) coregistered images depicted significantly high uptake of DT(GSHMe)2 at the BMG-1 tumor site. ROI analysis showed high tumor to contra lateral muscle ratio of 9.33 in PET imaging studies. Avid accumulation of radiotracer was observed at tumor versus inflammation site at 2 h post i.v. injection in an Ehrlich Ascites tumor (EAT) mice model, showing evident specificity for tumor. We propose DT(GSHMe)2 to be an excellent candidate for prognostication and tumor

  16. A futile cycle, formed between two ATP-dependant gamma-glutamyl cycle enzymes, gamma-glutamyl cysteine synthetase and 5-oxoprolinase: the cause of cellular ATP depletion in nephrotic cystinosis?

    PubMed

    Kumar, Akhilesh; Bachhawat, Anand Kumar

    2010-03-01

    Cystinosis, an inherited disease caused by a defect in the lysosomal cystine transporter (CTNS), is characterized by renal proximal tubular dysfunction. Adenosine triphosphate (ATP) depletion appears to be a key event in the pathophysiology of the disease, even though the manner in which ATP depletion occurs is still a puzzle. We present a model that explains how a futile cycle that is generated between two ATP-utilizing enzymes of the gamma-glutamyl cycle leads to ATP depletion. The enzyme gamma-glutamyl cysteine synthetase (gamma-GCS), in the absence of cysteine, forms 5-oxoproline (instead of the normal substrate, gamma-glutamyl cysteine) and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. Thus, in cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells. The model is also compatible with the differences seen in the human patients and the mouse model of cystinosis, where renal failure is not observed.

  17. Escherichia coli gamma-glutamyltranspeptidase mutants deficient in processing to subunits.

    PubMed

    Hashimoto, W; Suzuki, H; Nohara, S; Kumagai, H

    1992-11-30

    Arginyl residues 513 and 571 of Escherichia coli K-12 gamma-glutamyl-transpeptidase (EC 2.3.2.2) were substituted with alanyl and glycyl residues, respectively, by oligonucleotide-directed in vitro mutagenesis. Both mutants were devoid of the enzymatic activity. On Western blot analysis, we found that both mutants accumulated a gamma-glutamyltranspeptidase precursor which was not processed into large and small subunits in the periplasmic space of Escherichia coli.

  18. Identification and characterization of gamma-glutamylamine cyclotransferase, an enzyme responsible for gamma-glutamyl-epsilon-lysine catabolism.

    PubMed

    Oakley, Aaron J; Coggan, Marjorie; Board, Philip G

    2010-03-26

    Gamma-glutamylamine cyclotransferase (GGACT) is an enzyme that converts gamma-glutamylamines to free amines and 5-oxoproline. GGACT shows high activity toward gamma-glutamyl-epsilon-lysine, derived from the breakdown of fibrin and other proteins cross-linked by transglutaminases. The enzyme adopts the newly identified cyclotransferase fold, observed in gamma-glutamylcyclotransferase (GGCT), an enzyme with activity toward gamma-glutamyl-alpha-amino acids (Oakley, A. J., Yamada, T., Liu, D., Coggan, M., Clark, A. G., and Board, P. G. (2008) J. Biol. Chem. 283, 22031-22042). Despite the absence of significant sequence identity, several residues are conserved in the active sites of GGCT and GGACT, including a putative catalytic acid/base residue (GGACT Glu(82)). The structure of GGACT in complex with the reaction product 5-oxoproline provides evidence for a common catalytic mechanism in both enzymes. The proposed mechanism, combined with the three-dimensional structures, also explains the different substrate specificities of these enzymes. Despite significant sequence divergence, there are at least three subfamilies in prokaryotes and eukaryotes that have conserved the GGCT fold and GGCT enzymatic activity.

  19. N1N8-bis(gamma-glutamyl)spermidine cross-linking in epidermal-cell envelopes. Comparison of cross-link levels in normal and psoriatic cell envelopes.

    PubMed Central

    Martinet, N; Beninati, S; Nigra, T P; Folk, J E

    1990-01-01

    N1N8-Bis(gamma-glutamyl)spermidine was found in exhaustive proteolytic digests of isolated cell envelopes from human epidermis at levels comparable with those of epsilon-(gamma-glutamyl)lysine. Significantly higher than normal amounts of these compounds, particularly the bis(gamma-glutamyl)polyamine, were observed in envelopes from afflicted areas (scales) of psoriatic patients. These findings support the notions that N1N8-bis(gamma-glutamyl)spermidine, like epsilon-(gamma-glutamyl)lysine, functions in cell envelopes as an enzyme-generated protein cross-link and stabilizing force and that individuals with the chronic, recurrent skin disease, psoriasis, exhibit in involved epidermis abnormal cell-envelope-protein cross-linking. PMID:2241917

  20. Formation of Kokumi-Enhancing γ-Glutamyl Dipeptides in Parmesan Cheese by Means of γ-Glutamyltransferase Activity and Stable Isotope Double-Labeling Studies.

    PubMed

    Hillmann, Hedda; Behr, Jürgen; Ehrmann, Matthias A; Vogel, Rudi F; Hofmann, Thomas

    2016-03-02

    Recently, γ-glutamyl dipeptides (γ-GPs) were found to be responsible for the attractive kokumi flavor of Parmesan cheese (PC). Quantitation of γ-GPs and their parent amino acids in 13-, 24-, and 30-month ripened PC samples by LC-MS/MS and stable isotope dilution analysis (SIDA), in-cheese (13)C-labeling studies, followed by analysis of the γ-glutamyl transferase (GGT) activity revealed γ-GPs to be generated most efficiently after 24 months of ripening by a GGT-catalyzed transfer of the γ-glutamyl moiety of L-glutamine onto various acceptor amino acids released upon casein proteolysis. Following the identification of milk as a potential GGT source in PC, the functionality of the milk's GGT to generate the target γ-GPs was validated by stable isotope double-labeling (SIDL) experiments. Therefore, raw and heat-treated milk samples were incubated with L-glutamine-[U-(13)C] and acceptor amino acids (X) and the hetero- (γ-Glu-[(13)C5]-X) and homotranspeptidation products (γ-Glu-Gln-[(13)C10]) were quantitated by LC-MS/MS-SIDA using γ-Glu-Ala-[(13)C3] as the internal standard. High GGT activity to generate the γ-GPs and preference for L-phenylalanine and L-methionine as acceptor amino acids were found in raw milk and milk samples heat-treated for 10 min up to a maximum of 65 °C. In comparison, GGT activity and SIDL studies performed with inoculated Lactobacillus strains, including Lactobacillus harbinensis and Lactobacillus casei identified in PC by means of 16S rRNA gene sequencing, did not show any significant GGT activity and unequivocally demonstrated unpasteurized cow's milk, rather than microorganisms, as a key factor in γ-glutamyl dipeptide generation in Parmesan cheese.

  1. Ablation of Mrds1/Ofcc1 Induces Hyper-γ-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice

    PubMed Central

    Ohnishi, Tetsuo; Yamada, Kazuo; Watanabe, Akiko; Ohba, Hisako; Sakaguchi, Toru; Honma, Yota; Iwayama, Yoshimi; Toyota, Tomoko; Maekawa, Motoko; Watanabe, Kazutada; Detera-Wadleigh, Sevilla D.; Wakana, Shigeharu; Yoshikawa, Takeo

    2011-01-01

    Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as “the Japan Mouse Clinic”. No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT), a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs) located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia. PMID:22242126

  2. Cadmium-sulfide crystallites in Cd-. gamma. -glutamyl peptide complexes from Lycopersicon and Daucus

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

    Reese, R.N.; Winge, D.R.

    1989-04-01

    Hydroponically-grown tomato plants (Lycopersicon esculentum P. Mill. cv stone) and suspension-cultured carrot cells (Daucus carota L.) exposed to 100 {mu}M cadmium salts produced metal-{gamma}-glutamyl peptide complexes containing acid labile sulfur. The properties of the complexes resemble the Cd-{gamma}-glutamyl complexes from Schizosaccharomyces pombe and Candida glabrata, known to contain a CdS crystallite core. The crystallite core is stabilized by a coating of peptides of the general structure ({gamma}-Glu-Cys){sub n}-Gly. The Cd-peptide complexes contain predominantly peptides of n{sub 2}, n{sub 3}, n{sub 4} and n{sub 3}desGly. Zn-peptide complexes were also isolated from carrot cultures grown in MS medium supplemented with 2 mMmore » Zn and cysteine. Results of preliminary characterization of these complexes are consistent with the presence of a colloidal particle similar to that of the Cd-complexes.« less

  3. Biodistribution and catabolism of 18F-labelled isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine.

    PubMed

    Hultsch, C; Bergmann, R; Pawelke, B; Pietzsch, J; Wuest, F; Johannsen, B; Henle, T

    2005-12-01

    Isopeptide bonds between the epsilon-amino group of lysine and the gamma-carboxamide group of glutamine are formed during strong heating of pure proteins or, more important, by enzymatic reaction mediated by transglutaminases. Despite the wide use of a microbial transglutaminase in food biotechnology, up to now little is known about the metabolic fate of the isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine. In the present study, N-succinimidyl-4-[(18)F]fluorobenzoate was used to modify N(epsilon)-(gamma-glutamyl)-L-lysine at each of its two alpha-amino groups, resulting in the 4-[(18)F]fluorobenzoylated derivatives, for which biodistribution, catabolism, and elimination were investigated in male Wistar rats. A significant different biochemical behavior of the two labelled isopeptides was observed in terms of in vitro stability, in vivo metabolism as well as biodistribution. The results suggest that the metabolic fate of isopeptides is likely to be dependent on how they are reabsorbed - free or peptide bound.

  4. Relative tumour promoting activity of three polychlorinated biphenyls in rat liver.

    PubMed

    Hemming, H; Flodström, S; Wärngård, L; Bergman, A; Kronevi, T; Nordgren, I; Ahlborg, U G

    1993-08-02

    The relative tumour promoting activity of three structurally and toxicologically diverse polychlorinated biphenyls (3,4,5,3',4'-penta- 2,3,4,3',4'-penta- and 2,4,5,2',4',5'-hexachlorobiphenyl) was measured in an initiation/promotion assay in nitrosodiethylamine-initiated female Sprague-Dawley rats. The congeners under study were administered by once-weekly subcutaneous injections for 20 weeks. Evaluation of the development of gamma-glutamyl transpeptidase (GGT)- and glutation transferase P (GST-P)-positive hepatic foci showed that all congeners promoted altered hepatic foci, although 3,4,5,3',4'-pentachlorobiphenyl was far more potent. The volume fraction of the liver occupied by GGT-positive tissue in the 3,4,5,3',4'-pentachlorobiphenyl-treated animals (100 micrograms/kg per week) was 23%, while the volume fractions of altered liver tissue in the rats treated with 2,3,4,3',4'-pentachlorobiphenyl (5000 micrograms/kg per week) and 2,4,5,2',4',5'-hexaCB (20,000 micrograms/kg per week) were 1.2 and 2.3, respectively. The enhancement of GGT- and GST-P-positive foci was accompanied by an increased incidence of histological changes in the livers.

  5. Relation of serum γ-glutamyl transferase activity with copper in an adult population.

    PubMed

    Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

    2017-10-26

    The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, p<0.001). There was a positive correlation between serum γ-GGT activity and copper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, p<0.001; r=0.230, p=0.010). The results of multiple linear regression analysis showed that serum γ-GGT maintained a significantly positive correlation with copper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

  6. γ-Glutamyl transferase 7 is a novel regulator of glioblastoma growth.

    PubMed

    Bui, Timothy T; Nitta, Ryan T; Kahn, Suzana A; Razavi, Seyed-Mostafa; Agarwal, Maya; Aujla, Parvir; Gholamin, Sharareh; Recht, Lawrence; Li, Gordon

    2015-04-07

    Glioblastoma (GBM) is the most malignant primary brain tumor in adults, with a median survival time of one and a half years. Traditional treatments, including radiation, chemotherapy, and surgery, are not curative, making it imperative to find more effective treatments for this lethal disease. γ-Glutamyl transferase (GGT) is a family of enzymes that was shown to control crucial redox-sensitive functions and to regulate the balance between proliferation and apoptosis. GGT7 is a novel GGT family member that is highly expressed in brain and was previously shown to have decreased expression in gliomas. Since other members of the GGT family were found to be altered in a variety of cancers, we hypothesized that GGT7 could regulate GBM growth and formation. To determine if GGT7 is involved in GBM tumorigenesis, we modulated GGT7 expression in two GBM cell lines (U87-MG and U138) and monitored changes in tumorigenicity in vitro and in vivo. We demonstrated for the first time that GBM patients with low GGT7 expression had a worse prognosis and that 87% (7/8) of primary GBM tissue samples showed a 2-fold decrease in GGT7 expression compared to normal brain samples. Exogenous expression of GGT7 resulted in a 2- to 3-fold reduction in proliferation and anchorage-independent growth under minimal growth conditions (1% serum). Decreasing GGT7 expression using either short interfering RNA or short hairpin RNA consistently increased proliferation 1.5- to 2-fold. In addition, intracranial injections of U87-MG cells with reduced GGT7 expression increased tumor growth in mice approximately 2-fold, and decreased mouse survival. To elucidate the mechanism by which GGT7 regulates GBM growth, we analyzed reactive oxygen species (ROS) levels in GBM cells with modulated GGT7 expression. We found that enhanced GGT7 expression reduced ROS levels by 11-33%. Our study demonstrates that GGT7 is a novel player in GBM growth and that GGT7 can play a critical role in tumorigenesis by regulating

  7. Distribution of gamma-glutamyl-beta-alanylhistidine isopeptide in the macromolecular fractions of commercial meat extracts and correlation with the color of the macromolecular fractions.

    PubMed

    Kuroda, Motonaka; Harada, Tsutomu

    2002-03-27

    The measurement of gamma-glutamyl-beta-alanylhistidine isopeptide in the macromolecular fraction of various commercial meat extracts indicated that all of the commercial meat extracts tested contained the isopeptide, in concentrations ranging from 0.04 to 0.87 micromol/g of dry matter. This variation was suggested to be due to the differences between the processes of extraction and the differences in the initial amounts of carnosine. A positive correlation between the content of gamma-glutamyl-beta-alanylhistidine and the color of the macromolecular fraction was observed. These results suggested that gamma-glutamyl-beta-alanylhistidine is widely distributed in meat products and that the content can be used as an index of protein denaturation during the heating process.

  8. Influence of a Virgin Olive Oil versus Butter Plus Cholesterol-Enriched Diet on Testicular Enzymatic Activities in Adult Male Rats

    PubMed Central

    Segarra, Ana Belén; Martínez-Cañamero, Magdalena; Ramírez-Sánchez, Manuel

    2017-01-01

    The aim of the present work was to improve our knowledge on the mechanisms underlying the beneficial or deleterious effects on testicular function of the so-called Mediterranean and Western diet by analyzing glutamyl aminopeptidase (GluAP), gamma glutamyl transpeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) activities in testis, as enzymes involved in testicular function. Male Wistar rats (6 months old) were fed for 24 weeks with three different diets: standard (S), an S diet supplemented with virgin-olive-oil (20%) (VOO), or a S diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). At the end of the experimental period, plasma lipid profiled (total triglycerides, total cholesterol and cholesterol fractions (HDL, LDL and VDL)) were measured. Enzymatic activities were determined by fluorimetric methods in soluble (sol) and membrane-bound (mb) fractions of testicular tissue using arylamide derivatives as substrates. Results indicated an increase in plasmatic triglycerides, total cholesterol, LDL and VLDL in Bch. A significant increase of mb GluAP and GGT activities was also found in this diet in comparison with the other two diets. Furthermore, significant and positive correlations were established between these activities and plasma triglycerides and/or total cholesterol. These results support a role for testicular GluAP and GGT activities in the effects of saturated fat (Western diet) on testicular functions. In contrast, VOO increased sol DPP IV activity in comparison with the other two diets, which support a role for this activity in the effects of monounsaturated fat (Mediterranean diet) on testicular function. The present results strongly support the influence of fatty acids and cholesterol on testicular GluAP and GGT activities and also provide support that the reported beneficial influence of the Mediterranean diet in male fertility may be mediated in part by an increase of testicular sol DPP IV activity. PMID:28777292

  9. Influence of a Virgin Olive Oil versus Butter Plus Cholesterol-Enriched Diet on Testicular Enzymatic Activities in Adult Male Rats.

    PubMed

    Domínguez-Vías, Germán; Segarra, Ana Belén; Martínez-Cañamero, Magdalena; Ramírez-Sánchez, Manuel; Prieto, Isabel

    2017-08-04

    The aim of the present work was to improve our knowledge on the mechanisms underlying the beneficial or deleterious effects on testicular function of the so-called Mediterranean and Western diet by analyzing glutamyl aminopeptidase (GluAP), gamma glutamyl transpeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) activities in testis, as enzymes involved in testicular function. Male Wistar rats (6 months old) were fed for 24 weeks with three different diets: standard (S), an S diet supplemented with virgin-olive-oil (20%) (VOO), or a S diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). At the end of the experimental period, plasma lipid profiled (total triglycerides, total cholesterol and cholesterol fractions (HDL, LDL and VDL)) were measured. Enzymatic activities were determined by fluorimetric methods in soluble (sol) and membrane-bound (mb) fractions of testicular tissue using arylamide derivatives as substrates. Results indicated an increase in plasmatic triglycerides, total cholesterol, LDL and VLDL in Bch. A significant increase of mb GluAP and GGT activities was also found in this diet in comparison with the other two diets. Furthermore, significant and positive correlations were established between these activities and plasma triglycerides and/or total cholesterol. These results support a role for testicular GluAP and GGT activities in the effects of saturated fat (Western diet) on testicular functions. In contrast, VOO increased sol DPP IV activity in comparison with the other two diets, which support a role for this activity in the effects of monounsaturated fat (Mediterranean diet) on testicular function. The present results strongly support the influence of fatty acids and cholesterol on testicular GluAP and GGT activities and also provide support that the reported beneficial influence of the Mediterranean diet in male fertility may be mediated in part by an increase of testicular sol DPP IV activity.

  10. The Gamma-Glutamyl-Transpeptidase to Platelet Ratio Does not Show Advantages than APRI and Fib-4 in Diagnosing Significant Fibrosis and Cirrhosis in Patients With Chronic Hepatitis B: A Retrospective Cohort Study in China.

    PubMed

    Li, Qiang; Song, Jie; Huang, Yuxian; Li, Xinyan; Zhuo, Qibin; Li, Weixia; Chen, Chong; Lu, Chuan; Qi, Xun; Chen, Liang

    2016-04-01

    The gamma-glutamyl-transpeptidase to platelet ratio (GPR) is a new liver fibrosis model, which is reported to be more accurate than aspartate transaminase (AST) to platelet ratio index (APRI) and fibrosis index based on the four factors (Fib-4) for diagnosing significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) in West Africa. The aim of this study is to assess the diagnostic accuracy of GPR for significant fibrosis and cirrhosis in Chinese CHB patients, and explore whether GPR deserves to be popularized in China. A total of 372 CHB patients who underwent liver biopsies and routine laboratory tests were retrospectively studied. The Scheuer scoring system was adopted as the pathological standard of liver fibrosis. Using liver histology as a gold standard, the diagnostic accuracies of GPR, APRI, and Fib-4 for significant fibrosis and cirrhosis are evaluated and compared by the receiver operating characteristic (ROC) curves and the area under the ROC curves (AUROCs). Of these 372 patients, 176 (47.3%), 129 (34.7%), and 72 (19.4%) were classified as having significant fibrosis (≥ S2), severe fibrosis (≥ S3), and cirrhosis (S4), respectively. The AUROCs of GPR for significant fibrosis (0.72 vs. 0.78; P = 0.01), severe fibrosis (0.75 vs. 0.80; P = 0.04), and cirrhosis (0.78 vs. 0.83; P = 0.02) were lower than those of APRI. The AUROCs of GPR and Fib-4 for diagnosing significant fibrosis (0.72 vs. 0.70; P = 0.29), severe fibrosis (0.75 vs. 0.73; P = 0.33), and cirrhosis (0.78 vs. 0.75; P = 0.38) were comparable. GPR is a new serum diagnostic model for liver fibrosis and cirrhosis, but does not show advantages than APRI and Fib-4 in identifying significant fibrosis, severe fibrosis, and cirrhosis in CHB patients in China.

  11. Glutamyl-gamma-boronate inhibitors of bacterial Glu-tRNA(Gln) amidotransferase.

    PubMed

    Decicco, C P; Nelson, D J; Luo, Y; Shen, L; Horiuchi, K Y; Amsler, K M; Foster, L A; Spitz, S M; Merrill, J J; Sizemore, C F; Rogers, K C; Copeland, R A; Harpel, M R

    2001-09-17

    Analogues of glutamyl-gamma-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA(Gln) amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure-activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.

  12. Antihepatotoxic activity of Rosmarinus tomentosus in a model of acute hepatic damage induced by thioacetamide.

    PubMed

    Galisteo, M; Suárez, A; del Pilar Montilla, M; del Pilar Utrilla, M; Jiménez, J; Gil, A; Faus, M J; Navarro, M

    2000-11-01

    R. tomentosus is a vegetal species closely related to the culinary rosemary (R. officinalis), a plant reported to contain antihepatotoxic agents. A dried ethanol extract of the aerial parts of Rosmarinus tomentosus (Lamiaceae) and its major fraction separated by column chromatography (fraction F19) were evaluated for antihepatotoxic activity in rats with acute liver damage induced by a single oral dose of thioacetamide. Silymarin was used as a reference antihepatotoxic substance. Pre-treatment with R. tomentosus ethanol extract, fraction F19 or silymarin significantly reduced the impact of thioacetamide toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma-glutamyl transpeptidase activities compared with thioacetamide-treated animals (group T). Pre-treatment with R. tomentosus ethanol extract significantly reduced the impact of thioacetamide damage on alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Silymarin administration significantly reduced alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Fraction F19 administration reduced only alkaline phosphatase activity compared with group T. According to these data, R. tomentosus extract shows promising antihepatotoxic activity, suggesting the need to isolate the chemical principles responsible for this activity and to study this activity in a model of thioacetamide-induced cirrhosis. Copyright 2000 John Wiley & Sons, Ltd.

  13. Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.

    PubMed

    Tan, Ge; Yuan, Ruozhen; Hao, Zilong; Lei, Chunyan; Xiong, Yao; Xu, Mangmang; Liu, Ming

    2017-01-01

    Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. The influence of low protein diet on the testicular toxicity of di(2-ethylhexyl)phthalate.

    PubMed

    Tandon, R; Paramar, D; Singh, G B; Seth, P K; Srivastava, S P

    1992-12-01

    Oral administration of di(2-ethylhexyl)phthalate (DEHP) at 1000 mg/kg body weight to adult male albino rats maintained on low protein (LP) diet for 15 d resulted in a greater decrease in absolute and relative weights of the testis and in epididymal sperm count than in those rats maintained on a normal protein (NP) diet. A marked increase in the activity of testicular beta-glucuronidase and gamma-glutamyl transpeptidase (GGT) in the LP-fed animals suggested that LP diet enhanced the vulnerability of Sertoli cells towards DEHP. A greater decrease in the activity of testicular acid phosphatase, lactate dehydrogenase isoenzyme-X (LDH-X) and sorbitol dehydrogenase (SDH) in the LP-fed animals occurred in comparison to NP-fed animals. Degeneration of mature germinal cells in the LP-fed animals on exposure to DEHP suggested that LP diets enhance the susceptibility of the testis towards DEHP.

  15. A dose-up of ursodeoxycholic acid decreases transaminases in hepatitis C patients

    PubMed Central

    Sato, Shuichi; Miyake, Tatsuya; Tobita, Hiroshi; Oshima, Naoki; Ishine, Junichi; Hanaoka, Takuya; Amano, Yuji; Kinoshita, Yoshikazu

    2009-01-01

    AIM: To examine whether a dose-up to 900 mg of ursodeoxycholic acid (UDCA) decreases transaminases in hepatitis C patients. METHODS: From January to December 2007, patients with chronic hepatitis C or compensated liver cirrhosis with hepatitis C virus (HCV) (43-80 years old) showing positive serum HCV-RNA who had already taken 600 mg/d of UDCA were recruited into this study. Blood parameters were examined at 4, 8 and 24 wk after increasing the dose of oral UDCA from 600 to 900 mg/d. RESULTS: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) levels were significantly decreased following the administration of 900 mg/d as compared to 600 mg/d. The decrease in ALT from immediately before the dose-up of UDCA to 8 wk after the dose-up was 14.3 IU/L, while that for AST was 10.5 IU/L and for GGT was 9.8 IU/L. Platelet count tended to increase after the dose-up of UDCA, although it did not show a statistically significant level (P = 0.05). Minor adverse events were observed in 3 cases, although no drop-outs from the study occurred. CONCLUSION: Oral administration of 900 mg/d of UDCA was more effective than 600 mg/d for reducing ALT, AST, and GGT levels in patients with HCV-related chronic liver disease. PMID:19522030

  16. Tumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1.

    PubMed

    Reuter, Simone; Schnekenburger, Michael; Cristofanon, Silvia; Buck, Isabelle; Teiten, Marie-Hélène; Daubeuf, Sandrine; Eifes, Serge; Dicato, Mario; Aggarwal, Bharat B; Visvikis, Athanase; Diederich, Marc

    2009-02-01

    Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed. We found that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) induced GGT promoter transactivation, mRNA and protein synthesis, as well as enzymatic activity. Remicade, a clinically used anti-TNFalpha antibody, small interfering RNA (siRNA) against p50 and p65 nuclear factor-kappaB (NF-kappaB) isoforms, curcumin, a well characterized natural NF-kappaB inhibitor, as well as a dominant negative inhibitor of kappaB alpha (IkappaBalpha), prevented GGT activation at various levels, illustrating the involvement of this signaling pathway in TNFalpha-induced stimulation. Over-expression of receptor of TNFalpha-1 (TNFR1), TNFR-associated factor-2 (TRAF2), TNFR-1 associated death domain (TRADD), dominant negative (DN) IkappaBalpha or NF-kappaB p65 further confirmed GGT promoter activation via NF-kappaB. Linker insertion mutagenesis of 536 bp of the proximal GGT promoter revealed NF-kappaB and Sp1 binding sites at -110 and -78 relative to the transcription start site, responsible for basal GGT transcription. Mutation of the NF-kappaB site located at -110 additionally inhibited TNFalpha-induced promoter induction. Chromatin immunoprecipitation (ChIP) assays confirmed mutagenesis results and further demonstrated that TNFalpha treatment induced in vivo binding of both NF-kappaB and Sp1, explaining increased GGT expression, and led to RNA polymerase II recruitment under inflammatory conditions.

  17. Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

    PubMed

    Huang, Hao; Wang, Xue-Ping; Li, Xiao-Hui; Chen, Hao; Zheng, Xin; Lin, Jian-Hua; Kang, Ting; Zhang, Lin; Chen, Pei-Song

    2017-08-14

    The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

  18. Radiolabelling of isopeptide N epsilon-(gamma-glutamyl)-L-lysine by conjugation with N-succinimidyl-4-[18F]fluorobenzoate.

    PubMed

    Wüst, F; Hultsch, C; Bergmann, R; Johannsen, B; Henle, T

    2003-07-01

    The isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine 4 was labelled with 18F via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). A modified approach for the convenient synthesis of [18F]SFB was used, and [18F]SFB could be obtained in decay-corrected radiochemical yields of 44-53% (n = 20) and radiochemical purity >95% within 40 min after EOB. For labelling N(epsilon)-(gamma-glutamyl)-L-lysine with [18F]SFB the effects of isopeptide concentration, temperature, and pH were studied to determine the optimum reaction conditions. The coupling reaction was shown to be temperature and pH independent while being strongly affected by the isopeptide concentration. Using the optimized labelling conditions, in a typical experiment 1.3GBq of [18F]SFB could be converted into 447MBq (46%, decay-corrected) of [18F]fluorobenzoylated isopeptide within 45 min, including HPLC purification.

  19. Serum GGT activity and hsCRP level in patients with type 2 diabetes mellitus with good and poor glycemic control: An evidence linking oxidative stress, inflammation and glycemic control.

    PubMed

    Gohel, Mukesh G; Chacko, Anusha N

    2013-12-20

    Diabetes is undoubtedly one of the most challenging health problems in 21st century. Understanding the pathogenesis and preventing long term complications have been major goals of research in diabetes mellitus (DM). Research in the past few years has linked oxidative stress and inflammation to beta cell dysfunction. Aim of this study is to evaluate serum gamma-glutamyl transferase (GGT) activity (marker of oxidative stress) and high sensitivity C reactive protein (hsCRP) level (an inflammatory marker) in type 2 DM subjects with good and poor glycemic control. Further, we investigated correlation between serum GGT and hsCRP level with glycemic control (FBS, PP2BS, HbA1c) in subjects. A cross sectional study consists of 150 patients out of them 50 patients having type 2 DM with good control (Group II), 50 patients with type 2 DM with poor control (Group III) and 50 normal healthy control (Group I) were selected. Serum GGT, serum hsCRP, FBS, PP2BS, HbA1c, and other biochemical investigations include serum liver enzymes and lipids were measured. Mean serum GGT and hsCRP concentration were statistically significantly higher in group III patients compared to group I and group II subjects as well as increased in group II compared to group I (p < 0.001). Further significant positive correlation was observed between GGT and hsCRP concentration as well as both with HbA1c, FBS, and PP2BS. Oxidative stress and inflammation appears to be a key component and also associated with poor glycemic control and further pathogenesis of diabetes and its complications. All our finding suggesting a link between oxidative stress, inflammation and glycemic control in patient with type 2 diabetes mellitus.

  20. Effect of storage time at -20°C on markers used for assessment of renal damage in children: albumin, γ-glutamyl transpeptidase, N-acetyl-β-D-glucosaminidase and α1-microglobulin.

    PubMed

    Trachtenberg, Felicia; Barregard, Lars

    2010-11-01

    The objective of this study is to examine the influence of storage time at -20°C on the concentration of albumin, γ-glutamyl transpeptidase (γ-GT), N-acetyl-β-D-glucosaminidase (NAG), α(1)-microglobulin (A1M) and creatinine in a large sample of healthy children. The New England Children's Amalgam Trial followed 534 children, aged 6-10 at baseline, for 5 years, with annual urine collections. Urine samples were analysed for creatinine, albumin, γ-GT, NAG and A1M concentrations. Repeated measures analysis of covariance was used to model the effect of storage time on these concentrations. The γ-GT concentration decreased significantly with storage time at -20°C. There was also a limited decrease in NAG. Albumin, A1M and creatinine concentrations did not appear to be affected by storage time at -20°C. If it is necessary to interpret results from samples stored for a long time at -20°C, it is advisable to account for storage time in statistical models.

  1. Ursodeoxycholic Acid for Treatment of Enlarged Polycystic Liver.

    PubMed

    Iijima, Takashi; Hoshino, Junichi; Suwabe, Tatsuya; Sumida, Keiichi; Mise, Koki; Kawada, Masahiro; Imafuku, Aya; Hayami, Noriko; Hiramatsu, Rikako; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Ubara, Yoshifumi

    2016-02-01

    Patients with autosomal dominant polycystic kidney disease and polycystic liver disease (PLD) often have elevated serum levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). Ursodeoxycholic acid (UDCA) is used to treat biliary tract diseases, but its effect on PLD remains unclear. UDCA was administered for 1 year at a dose of 300 mg daily to seven PLD patients with elevated ALP or GGT levels who were selected for this treatment by experienced clinicians. Laboratory data and liver volumes were compared among three time points: 1 year before UDCA treatment, at the start of UDCA therapy, and 1 year after the start of therapy. Median GGT did not show a significant change between 1 year before UDCA (180 IU/L) and the start of UDCA therapy (209 IU/L), but it decreased significantly to 98 IU/L after 1 year of UDCA therapy (P = 0.015 vs. the start of therapy). ALP showed a significant increase from 1 year before UDCA (456 IU/L) to the start of UDCA therapy (561 IU/L), and then decreased significantly after 1 year of UDCA therapy (364 IU/L). Median liver volume did not show any significant changes among these three time points of assessment. UDCA may be effective for reducing biliary enzyme levels and inhibiting the growth of liver cysts in patients with PLD. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  2. Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer.

    PubMed

    Kawakami, Kyojiro; Fujita, Yasunori; Matsuda, Yoko; Arai, Tomio; Horie, Kengo; Kameyama, Koji; Kato, Taku; Masunaga, Koichi; Kasuya, Yutaka; Tanaka, Masashi; Mizutani, Kosuke; Deguchi, Takashi; Ito, Masafumi

    2017-05-05

    Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients. Exosomes isolated by differential centrifugation from the culture medium of androgen-dependent LNCaP prostate cancer cell line and its sublines of partially androgen-independent C4, androgen-independent C4-2 and bone metastatic C4-2B were subjected to iTRAQ-based proteomic analysis. Exosomes were also isolated by immunocapture and separated by size exclusion chromatography and density gradient centrifugation. Protein expression was determined by Western blot analysis. GGT activity was measured using a fluorescent probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG). Immunohistochemical analysis of tissues was performed using anti-GGT1 antibody. Among proteins upregulated in C4-2 and C4-2B cells than in LNCaP cells, we focused on gamma-glutamyltransferase 1 (GGT1), a cell-surface enzyme that regulates the catabolism of extracellular glutathione. The levels of both GGT1 large and small subunits were elevated in exosomes isolated from C4-2 and C4-2B cells by differential centrifugation and by immunocapture with anti-CD9 or -prostate-specific membrane antigen (PSMA) antibody. In cell lysates and exosomes, GGT1 expression correlated with GGT activity. Size exclusion chromatography of human serum demonstrated the presence of GGT activity and GGT1 subunits in fractions positive for CD9. Density gradient centrifugation revealed the co-presence of GGT1 subunits with CD9 in exosomes isolated by differential centrifugation from human serum. Since GGT activity correlated with GGT1 expression in serum exosomes isolated by differential centrifugation, we measured serum exosomal GGT activity in patients. Unexpectedly, we found that serum exosomal GGT activity was

  3. [Dynamic change study of dermatitis medicamentosa-like of trichloroethylene patients with liver damage].

    PubMed

    Liu, Wei; Zhang, Yan-fang; Zhang, Zhi-min; Li, Pei-mao; Jiang, Xiao-dong; Zhou, Gui-feng; Liu, Jian-jun

    2011-10-01

    Observing the dynamic change characteristics of serum liver function indexes in occupational dermatitis medicamentosa-like of trichloroethylene patients with liver damage, we can underlie for guiding therapy, prognosis and mechanism of dermatitis medicamentosa-like of trichloroethylene patients with liver damage. We collected serum of 10 cases of occupational dermatitis medicamentosa-like of trichloro-ethylene patients with liver damage from different time points since they were hospitalized, using automatic biochemistry analyzer to detect total protein (TP), albumin (ALB), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), albumin/globulin ratio etc 11 liver function biochemical indicators. We used Excel to establish database, professional drawing software gnuplot to draw dynamic variation diagram of each index. The variation range of 11 liver function indexes of 10 cases was TP 43.2-74.2 g/L, ALB 24.6-44.6 g/L, A/G 0.77-2.10, TBIL 3.7-268.2 umol/L, DBIL 1.0-166.0 umol/L, IBIL 2.4 -167.5 umol/L, ALT 11-5985 U/L, AST 14-5586 U/L, GGT 15-1500 U/L, ALP 35-309 U/L, S/L 0.07-1.94, respectively. TBIL, DBIL, ALT, AST, GGT, ALP concentration significantly increased, especially ALT, AST, GGT, ALT topped 5985 U/L, AST topped 5586 U/L, GGT topped 1500 U/L. But TP, ALB and S/L significantly decreased, TP lowest to 43.2 g/L, S/L lowest to 0.07. A/G basically remained unchanged, but IBIL didn't change regularly. The early liver damage in dermatitis medicamentosa-like of trichloroethylene patients was serious, and repeatedly attacked, so we should lead to enough attention to the clinical work and prevention. This also provided the basis for studying the mechanism of trichloroethylene poisoning.

  4. Predictive factors for the severity of liver fibrosis in patients with chronic hepatitis C and moderate alcohol consumption.

    PubMed

    Vădan, Roxana; Gheorghe, Liana; Becheanu, Gabriel; Iacob, Răzvan; Iacob, Speranţa; Gheorghe, Cristian

    2003-09-01

    Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus. We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis. From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis. Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

  5. Successful synthesis of active human coagulation factor VII by co-expression of mammalian gamma-glutamyl carboxylase and modification of vit.K cycle in Drosophila Schneider S2 cells.

    PubMed

    Nagahashi, Kotomi; Umemura, Kazuo; Kanayama, Naohiro; Iwaki, Takayuki

    2017-04-01

    Mammalian gamma-glutamyl carboxylase and reduced vitamin K are indispensable for synthesis of mature mammalian vitamin K dependent proteins including some of blood coagulation factors (factors II, VII, IX, and X). It was well known that Drosophila melanogaster expressed gamma-glutamyl carboxylase and possessed a vit.K cycle although native substrates for them have not been identified yet. Despite the potential capability of gamma carboxylation in D. melanogaster derived cells such as S2 cells, Drosophila gamma-glutamyl carboxylase failed to gamma carboxylate a peptide fused to the human coagulation factor IX propeptide. Thus, it had been believed that the Drosophila system was not adequate to synthesize mammalian vit.K dependent proteins. Indeed, we previously attempted to synthesize biologically active factor VII in S2 cells although we were not able to obtain it. However, recently, a successful transient expression of biologically active human factor IX from S2 cells was reported. In the present study, several expression vectors which enable expressing mammalian GGCX, VKORC1, and/or PDIA2 along with F7 were developed. S2 cells transfected with pMKA85, pMAK86, and pMAK219 successfully synthesized active FVII. Thus, mammalian GGCX was indispensable to synthesize active FVII while mammalian VKORC1 and PDIA2 were not critical but supportive factors for S2 cells.

  6. Enzyme activities in plasma, liver, and kidney of black ducks and mallards

    USGS Publications Warehouse

    Franson, J. Christian

    1982-01-01

    Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were measured in plasma, liver, and kidney, and gamma-glutamyl transferase (GGT) was measured in liver and kidney of black ducks (Anas rubripes). Activities of ALT, AST, GGT, and ornithine carbamyl transferase (OCT) were assayed in plasma, liver, and kidney of game-farm mallards (Anas platyrhynchos). Appreciable OCT and AST activity occurred in both liver and kidney. Activities of ALT, CPK, ALP and GGT were higher in kidney, while LDH was higher in liver, GGT was detected in plasma from one of four mallards.

  7. Pattern of γ-glutamyl transferase activity in cow milk throughout lactation and relationships with metabolic conditions and milk composition.

    PubMed

    Calamari, L; Gobbi, L; Russo, F; Cappelli, F Piccioli

    2015-08-01

    The main objective of this experiment was to study the γ-glutamyl transferase (GGT) activity in milk during lactation and its relationship with metabolic status of dairy cows, milk yield, milk composition, and cheesemaking properties. The study was performed in a tied stall barn and involved 20 lactations from 12 healthy multiparous Italian Friesian dairy cows. During lactation starting at d 10, milk samples were collected weekly and analyzed for composition, somatic cells count, titratable acidity, and milk coagulation properties. The GGT activity was measured in defatted samples. Blood samples were collected weekly to assess biochemical indicators related to energy, protein, and mineral metabolism, markers of inflammation and some enzyme activities. The lactations of each cow were retrospectively categorized into 2 groups according to their milk GGT activity value through lactation. A median value of GGT activity in the milk of all lactations was calculated (3,045 U/L), and 10 lactations with lower GGT activity were classified as low while 10 lactations with greater GGT activity were classified as high. The average value of milk GGT activity during lactation was 3,863 and 3,024 U/L for high and low, respectively. The GGT activity decreased in early lactation and reached minimum values in the second month (3,289 and 2,355 U/L for high and low, respectively). Thereafter GGT activity increased progressively, reaching values in late lactation of 4,511 and 3,540 U/L in high and low, respectively. On average, milk yield was 40.81 and 42.76 kg/d in high and low, respectively, and a negative partial correlation with milk GGT activity was observed. A greater milk protein concentration was observed in high (3.39%) compared with low (3.18%), and a positive partial correlation with milk GGT activity was observed. Greater titratable acidity in high than that in low (3.75 vs. 3.45 degrees Soxhlet-Henkel/50 mL, respectively) was also observed. Plasma glucose was greater in

  8. GC-MS Analysis: In Vivo Hepatoprotective and Antioxidant Activities of the Essential Oil of Achillea biebersteinii Afan. Growing in Saudi Arabia.

    PubMed

    Al-Said, Mansour S; Mothana, Ramzi A; Al-Yahya, Mohammed M; Rafatullah, Syed; Al-Sohaibani, Mohammed O; Khaled, Jamal M; Alatar, Abdulrahman; Alharbi, Naiyf S; Kurkcuoglu, Mine; Baser, Husnu C

    2016-01-01

    Liver disease is a worldwide problem. It represents one of the main causes of morbidity and mortality in humans. Achillea biebersteinii is used as herbal remedy for various ailments including liver diseases. But the scientific basis for its medicinal use remains unknown. Thus, this research was undertaken to evaluate the efficiency of A. biebersteinii essential oil (ABEO) (0.2 mL/kg) in the amelioration of CCl4-induced hepatotoxicity in rodent model. Moreover, the chemical content of the oil was investigated using GC and GC-MS. The following biochemical parameters were evaluated: serum glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), gamma-glutamyl-transpeptidase (γ-GGT), alkaline phosphatase (ALP), and total bilirubin. Furthermore, lipid profile, malondialdehyde (MDA), nonprotein sulfhydryl (NP-SH), and total protein (TP) contents in liver tissue were estimated. 44 components (92.0%) of the total oil have been identified by GC-MS analysis where α-terpinene and p-cymene were the most abundant. The high serum enzymatic (GOT, GPT, GGT, and ALP) and bilirubin concentrations as well as the level of MDA, NP-SH, and TP contents in liver tissues were significantly reinstated towards normalization by the ABEO. Histopathological study further confirmed these findings. In addition, ABEO showed mild antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and β-carotene-linoleic acid assays.

  9. Isolation of Notl sites from chromosome 22q11

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

    Ten Hoeve, J.; Groffen, J.; Heisterkamp, N.

    1993-12-01

    Chromosome 22q11 contains a large number of interesting loci, including genes associated with cancer and developmental defects. The region is also the site of the lambda immunoglobulin variable and constants regions and the BCR, [gamma]-glutamyl transpeptidase, and GGT-like activity multigene families. Because of the complexities associated with mapping highly related gene families, the authors have examined the utility of mapping large areas of DNA using a defined approach. A total of 21 complete NotI sites from band q11 were cloned and ordered into six noncontiguous clusters of sites using a combination of somatic cell hybrid panels, NotI jumping and linkingmore » libraries, and fluorescence in situ hybridization. The largest cluster spanned an estimated 2 Mb of NotI fragments, the smallest 115 kb. Approximately 3.5 Mb of band q11 could be examined for rearrangements in NotI restriction enzyme fragments. A number of conserved sequences, two genes, and a minimum of two families of related sequences were identified adjacent to NotI sites. 51 refs., 5 figs., 4 tabs.« less

  10. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals.

    PubMed

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Forman, Henry Jay; Crocker, Daniel E; Ortiz, Rudy M

    2011-04-15

    Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin-angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], γ-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in γ-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40-50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities and a 30% increase in PrxVI content. Plasma γ-glutamyl glutamine, γ-glutamyl isoleucine and γ-glutamyl methionine also increased with fasting whereas glutamate and glutamine decreased. Results indicate that GSH biosynthesis increases with fasting and that GSH contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals.

  11. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals

    PubMed Central

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Forman, Henry Jay; Crocker, Daniel E.; Ortiz, Rudy M.

    2011-01-01

    SUMMARY Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin–angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], γ-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in γ-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40–50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities and a 30% increase in PrxVI content. Plasma γ-glutamyl glutamine, γ-glutamyl isoleucine and γ-glutamyl methionine also increased with fasting whereas glutamate and glutamine decreased. Results indicate that GSH biosynthesis increases with fasting and that GSH contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals. PMID:21430206

  12. Enzymatic synthesis of γ-L-glutamyl-S-allyl-L-cysteine, a naturally occurring organosulfur compound from garlic, by Bacillus licheniformis γ-glutamyltranspeptidase.

    PubMed

    Chen, Yi-Yu; Lo, Huei-Fen; Wang, Tzu-Fan; Lin, Min-Guan; Lin, Long-Liu; Chi, Meng-Chun

    2015-01-01

    In the practical application of Bacillus licheniformis γ-glutamyltranspeptidase (BlGGT), we describe a straightforward enzymatic synthesis of γ-L-glutamyl-S-allyl-L-cysteine (GSAC), a naturally occurring organosulfur compound found in garlic, based on a transpeptidation reaction involving glutamine as the γ-glutamyl donor and S-allyl-L-cysteine as the acceptor. With the help of thin layer chromatography technique and computer-assisted image analysis, we performed the quantitative determination of GSAC. The optimum conditions for a biocatalyzed synthesis of GSAC were 200 mM glutamine, 200 mM S-allyl-L-cysteine, 50 mM Tris-HCl buffer (pH 9.0), and BlGGT at a final concentration of 1.0 U/mL. After a 15-h incubation of the reaction mixture at 60 °C, the GSAC yield for the free and immobilized enzymes was 19.3% and 18.3%, respectively. The enzymatic synthesis of GSAC was repeated under optimal conditions at 1-mmol preparative level. The reaction products together with the commercially available GSAC were further subjected to an ESI-MS/MS analysis. A significant signal with m/z of 291.1 and the protonated fragments at m/z of 73.0, 130.1, 145.0, and 162.1 were observed in the positive ESI-MS/MS spectrum, which is consistent with those of the standard compound. These results confirm the successful synthesis of GSAC from glutamine and S-allyl-L-cysteine by BlGGT. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. [Liver enzymes elevation: etiologic study and efficiency of a single-act office visit].

    PubMed

    Bendezú García, Rogger Álvaro; Casado Martín, Marta; Lázaro Sáez, Marta; Patrón Román, Gustavo Óliver; Gálvez Miras, Alejandra; Rodríguez Laiz, Gonzalo P; González Sánchez, Mercedes; Vega Sáenz, José Luis

    2013-01-01

    Liver enzyme (LE) elevation is a common finding in routine blood analysis. There is very little information on the most prevalent causes of these alterations in our population. In addition, a number of tests and several visits to the specialist are required to reach a diagnosis. For these reasons, we designed a protocol to streamline the evaluation of patients with LE elevations in a single-act office visit. From March 2008 until June 2010, we studied all patients with incidental LE elevation (isolated transaminase elevation, combined elevation of alkaline phosphatase [FA] and gamma-glutamyl transpeptidase [GGT], or isolated elevation of GGT) who were referred by their primary care physicians. At the time of referral, a complete biochemistry analysis was performed (LE, viral serology, autoantibodies, ceruloplasmin, iron metabolism, alpha-1-antitrypsin and thyroid hormones) and the patients underwent an abdominal ultrasound scan on the day of the office evaluation by the hepatologist. A total of 427 patients were included in our study. The most common cause of transaminase elevation was non-alcoholic fatty liver disease (NAFLD) (40%), followed by alcohol intake (17%), and hepatitis C virus infection (13%). Elevated GGT levels were most commonly related to NAFLD (30%), closely followed by alcohol intake (27%), and hepatotoxicity (8%). Combined elevation of GGT and FA was associated with NAFLD (21%), alcohol (17%), and hepatotoxicity (11%). Self-limited elevation was seen in 9% of the patients and we could not identify a definite cause in 11%. A definitive diagnosis was reached in 79% of the patients. The single-act office visit has proven to be efficient, yielding a diagnosis in most of the patients. The most common cause of elevated LE was NAFLD. Transaminase elevation must be confirmed before a more thorough work-up is started. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  14. The gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis and cirrhosis in HBeAg-positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China.

    PubMed

    Li, Q; Li, W; Huang, Y; Chen, L

    2016-11-01

    The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a new serum diagnostic model, which is reported to be more accurate than aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (Fib-4) for the diagnosis of significant fibrosis and cirrhosis in chronic HBV infection (CHBVI) patients in West Africa. To evaluate the performance of the GPR model for the diagnosis of liver fibrosis and cirrhosis in HBeAg-positive CHBVI patients with high HBV DNA (≥5 log 10 copies/mL) and normal or mildly elevated alanine transaminase (ALT) (≤2 times upper limit of normal (ULN)) in China. A total of 1521 consecutive CHBVI patients who underwent liver biopsies and routine laboratory tests were retrospectively screened. Of these patients, 401 treatment naïve HBeAg-positive patients with HBV DNA≥5 log 10 copies/mL and ALT≤2 ULN were included. The METAVIR scoring system was adopted as the pathological diagnosis standard of liver fibrosis. Using liver histology as a gold standard, the performances of GPR, APRI, and Fib-4 for the diagnosis of liver fibrosis and cirrhosis were evaluated and compared by receiver operating characteristic (ROC) curves and the area under the ROC curves (AUROCs). Of 401 patients, 121 (30.2%), 49 (12.2%) and 17 (4.2%) were classified as having significant fibrosis (≥F2), severe fibrosis (≥F3) and cirrhosis (=F4), respectively. After estimating the AUROC to predict significant fibrosis, the performance of GPR (AUROC=0.66, 95% CI 0.60-0.72) was higher than APRI (AUROC=0.58, 95% CI 0.52-0.64, P=.002) and Fib-4 scores (AUROC=0.54, 95% CI 0.47-0.60, P<.001). After estimating the AUROC to predict severe fibrosis, the performance of GPR (AUROC=0.71, 95% CI 0.63-0.80) was also higher than APRI (AUROC=0.65, 95% CI 0.56-0.73, P=.003) and Fib-4 scores (AUROC=0.67, 95% CI 0.58-0.75, P=.001). After estimating the AUROC to predict cirrhosis, the performance of GPR (AUROC=0.73, 95% CI 0.56-0.88) was higher than

  15. Seed storage protein deficiency improves sulfur amino acid content in common bean (Phaseolus vulgaris L.): redirection of sulfur from gamma-glutamyl-S-methyl-cysteine.

    PubMed

    Taylor, Meghan; Chapman, Ralph; Beyaert, Ronald; Hernández-Sebastià, Cinta; Marsolais, Frédéric

    2008-07-23

    The contents of sulfur amino acids in seeds of common bean ( Phaseolus vulgaris L.) are suboptimal for nutrition. They accumulate large amounts of a gamma-glutamyl dipeptide of S-methyl-cysteine, a nonprotein amino acid that cannot substitute for methionine or cysteine in the diet. Protein accumulation and amino acid composition were characterized in three genetically related lines integrating a progressive deficiency in major seed storage proteins, phaseolin, phytohemagglutinin, and arcelin. Nitrogen, carbon, and sulfur contents were comparable among the three lines. The contents of S-methyl-cysteine and gamma-glutamyl-S-methyl-cysteine were progressively reduced in the mutants. Sulfur was shifted predominantly to the protein cysteine pool, while total methionine was only slightly elevated. Methionine and cystine contents (mg per g protein) were increased by up to ca. 40%, to levels slightly above FAO guidelines on amino acid requirements for human nutrition. These findings may be useful to improve the nutritional quality of common bean.

  16. Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4[S

    PubMed Central

    Lukic, Ana; Ji, Jie; Idborg, Helena; Samuelsson, Bengt; Palmberg, Lena

    2016-01-01

    Leukotrienes (LTs) play major roles in lung immune responses, and LTD4 is the most potent agonist for cysteinyl LT1, leading to bronchoconstriction and tissue remodeling. Here, we studied LT crosstalk between myeloid cells and pulmonary epithelial cells. Monocytic cells (Mono Mac 6 cell line, primary dendritic cells) and eosinophils produced primarily LTC4. In coincubations of these myeloid cells and epithelial cells, LTD4 became a prominent product. LTC4 released from the myeloid cells was further transformed by the epithelial cells in a transcellular manner. Formation of LTD4 was rapid when catalyzed by γ-glutamyl transpeptidase (GGT)1 in the A549 epithelial lung cancer cell line, but considerably slower when catalyzed by GGT5 in primary bronchial epithelial cells. When A549 cells were cultured in the presence of IL-1β, GGT1 expression increased about 2-fold. Also exosomes from A549 cells contained GGT1 and augmented LTD4 formation. Serine-borate complex (SBC), an inhibitor of GGT, inhibited conversion of LTC4 to LTD4. Unexpectedly, SBC also upregulated translocation of 5-lipoxygenase (LO) to the nucleus in Mono Mac 6 cells, and 5-LO activity. Our results demonstrate an active role for epithelial cells in biosynthesis of LTD4, which may be of particular relevance in the lung. PMID:27436590

  17. Selenium uptake through cystine transporter mediated by glutathione conjugation.

    PubMed

    Tobe, Takao; Ueda, Koji; Aoki, Akira; Okamoto, Yoshinori; Kojima, Nakao; Jinno, Hideto

    2017-01-01

    Selenium (Se) is an essential trace element and is regarded as a protective agent against cancer. In particular, antioxidant effects of selenoenzymes contribute to cancer prevention. Se can also produce reactive oxygen species and, thereby, exert cancer-selective cytotoxicity. Selenodiglutathione (SDG) is a primary Se metabolite conjugated to two glutathione (GSH) moieties. SDG increases intracellular Se accumulation and is more toxic than selenous acid (H 2 SeO 3 ), but the mechanisms for importing Se compounds into cells are not fully understood. Here, we propose a novel mechanism for importing Se, in the form of SDG. Cellular intake of Se compounds was assessed based on Se accumulation, as detected by ICP-MS. SDG incorporation was decreased in the presence of thiols (GSH, cysteine or their oxidized forms, GSSG and cystine), whereas H 2 SeO 3 uptake was increased by addition of GSH or cysteine. Cellular SDG uptake was decreased by pretreatment with specific inhibitors against gamma-glutamyl transpeptidase (GGT) or the cystine/glutamate antiporter (system x c - ). Furthermore, siRNA against xCT, which is the light chain component of system x c - , significantly decreased SDG incorporation. These data suggest an involvement of SDG in Se incorporation, with SDG processed at the cell surface by GGT, leading to formation of selenodicysteine which, in turn, is likely to be imported via xCT. Because GGT and xCT are highly expressed in cancer cells, these mechanisms mediated by the cystine transporter might underlie the cancer-selective toxicity of Se. In addition, the system described in our study appears to represent a physiological transport mechanism for the essential element Se.

  18. Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-gamma-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan.

    PubMed Central

    Mengin-Lecreulx, D; van Heijenoort, J; Park, J T

    1996-01-01

    A gene, mpl, encoding UDP-N-acetylmuramate:L-alanyl-gamma-D-glutamyl-meso-diaminopimelat e ligase was recognized by its amino acid sequence homology with murC as the open reading frame yjfG present at 96 min on the Escherichia coli map. The existence of such an enzymatic activity was predicted from studies indicating that reutilization of the intact tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate occurred and accounted for well over 30% of new cell wall synthesis. Murein tripeptide ligase activity could be demonstrated in crude extracts, and greatly increased activity was produced when the gene was cloned and expressed under control of the trc promoter. A null mutant totally lacked activity but was viable, showing that the enzyme is not essential for growth. PMID:8808921

  19. Evaluation of a controlled drinking minimal intervention for problem drinkers in general practice (the DRAMS scheme)

    PubMed Central

    Heather, Nick; Campion, Peter D.; Neville, Ronald G.; Maccabe, David

    1987-01-01

    Sixteen general practitioners participated in a controlled trial of the Scottish Health Education Group's DRAMS (drinking reasonably and moderately with self-control) scheme. The scheme was evaluated by randomly assigning 104 heavy or problem drinkers to three groups – a group participating in the DRAMS scheme (n = 34), a group given simple advice only (n = 32) and a non-intervention control group (n = 38). Six month follow-up information was obtained for 91 subjects (87.5% of initial sample). There were no significant differences between the groups in reduction in alcohol consumption, but patients in the DRAMS group showed a significantly greater reduction in a logarithmic measure of serum gamma-glutamyl-transpeptidase than patients in the group receiving advice only. Only 14 patients in the DRAMS group completed the full DRAMS procedure. For the sample as a whole, there was a significant reduction in alcohol consumption, a significant improvement on a measure of physical health and well-being, and significant reductions in the logarithmic measure of serum gamma-glutamyl transpeptidase and in mean corpuscular volume. The implications of these findings for future research into controlled drinking minimal interventions in general practice are discussed. PMID:3448228

  20. Novel Derivative of Bardoxolone Methyl Improves Safety for the Treatment of Diabetic Nephropathy.

    PubMed

    Huang, Zhangjian; Mou, Yi; Xu, Xiaojun; Zhao, Di; Lai, Yisheng; Xu, Yuwen; Chen, Cen; Li, Ping; Peng, Sixun; Tian, Jide; Zhang, Yihua

    2017-11-09

    Currently, no effective and safe medicines are available to treat diabetic nephropathy (DN). Bardoxolone methyl (CDDO-Me) has displayed promising anti-DN activity as well as serious side effects in clinical trials, probably because the highly reactive α-cyano-α,β-unsaturated ketone (CUK) in ring A of CDDO-Me can covalently bind to thiol functionalities in many biomacromolecules. In this study, we designed and synthesized a γ-glutamyl transpeptidase (GGT)-based and CUK-modified derivative of CDDO-Me (2) to address this issue. 2 can be specifically cleaved by GGT, which is highly expressed in the kidney, to liberate CDDO-Me in situ. It should be noted that 2 exhibited anti-DN efficacy comparable to that of CDDO-Me with much less toxicity in cells and db/db mice, suggesting that its safety is better than CDDO-Me. Our findings not only reveal the therapeutic potential of 2 but also provide a strategy to optimize other synthetic molecules or natural products bearing a pharmacophore like CUK to achieve safer pharmaceutical drugs.

  1. Role of epimorphin in bile duct formation of rat liver epithelial stem-like cells: involvement of small G protein RhoA and C/EBPβ.

    PubMed

    Jia, Yali; Yao, Hailei; Zhou, Junnian; Chen, Lin; Zeng, Quan; Yuan, Hongfeng; Shi, Lei; Nan, Xue; Wang, Yunfang; Yue, Wen; Pei, Xuetao

    2011-11-01

    Epimorphin/syntaxin 2 is a high conserved and very abundant protein involved in epithelial morphogenesis in various organs. We have shown recently that epimorphin (EPM), a protein exclusively expressed on the surface of hepatic stellate cells and myofibroblasts of the liver, induces bile duct formation of hepatic stem-like cells (WB-F344 cells) in a putative biophysical way. Therefore, the aim of this study was to present some of the molecular mechanisms by which EPM mediates bile duct formation. We established a biliary differentiation model by co-culture of EPM-overexpressed mesenchymal cells (PT67(EPM)) with WB-F344 cells. Here, we showed that EPM could promote WB-F344 cells differentiation into bile duct-like structures. Biliary differentiation markers were also elevated by EPM including Yp, Cx43, aquaporin-1, CK19, and gamma glutamyl transpeptidase (GGT). Moreover, the signaling pathway of EPM was analyzed by focal adhesion kinase (FAK), extracellular regulated kinase 1/2 (ERK1/2), and RhoA Western blot. Also, a dominant negative (DN) RhoA-WB-F344 cell line (WB(RhoA-DN)) was constructed. We found that the levels of phosphorylation (p) of FAK and ERK1/2 were up-regulated by EPM. Most importantly, we also showed that RhoA is necessary for EPM-induced activation of FAK and ERK1/2 and bile duct formation. In addition, a dual luciferase-reporter assay and CHIP assay was performed to reveal that EPM regulates GGT IV and GGT V expression differentially, possibly mediated by C/EBPβ. Taken together, these data demonstrated that EPM regulates bile duct formation of WB-F344 cells through effects on RhoA and C/EBPβ, implicating a dual aspect of this morphoregulator in bile duct epithelial morphogenesis. Copyright © 2011 Wiley-Liss, Inc.

  2. Detecting early kidney damage in horses with colic by measuring matrix metalloproteinase -9 and -2, other enzymes, urinary glucose and total proteins

    PubMed Central

    Arosalo, Bela M; Raekallio, Marja; Rajamäki, Minna; Holopainen, Elina; Kastevaara, Tuulia; Salonen, Hanna; Sankari, Satu

    2007-01-01

    Background The aim of the study was to investigate urine matrix metalloproteinase (MMP-2 and -9) activity, alkaline phosphatase/creatinine (U-AP/Cr) and gamma-glutamyl-transpeptidase/creatinine (U-GGT/Cr) ratios, glucose concentration, and urine protein/creatinine (U-Prot/Cr) ratio and to compare data with plasma MMP-2 and -9 activity, cystatin-C and creatinine concentrations in colic horses and healthy controls. Horses with surgical colic (n = 5) were compared to healthy stallions (n = 7) that came for castration. Blood and urine samples were collected. MMP gelatinolytic activity was measured by zymography. Results We found out that horses with colic had significantly higher urinary MMP-9 complex and proMMP-9 activities than horses in the control group. Colic horses also had higher plasma MMP-2 activity than the control horses. Serum creatinine, although within reference range, was significantly higher in the colic horses than in the control group. There was no significant increase in urinary alkaline phosphatase, gamma-glutamyltranspeptidase or total proteins in the colic horses compared to the control group. A human cystatin-C test (Dako Cytomation latex immunoassay® based on turbidimetry) did not cross react with equine cystatin-C. Conclusion The results indicate that plasma MMP-2 may play a role in the pathogenesis of equine colic and urinary MMP-9 in equine kidney damage. PMID:17244354

  3. p-aminophenol nephrotoxicity: biosynthesis of toxic glutathione conjugates.

    PubMed

    Klos, C; Koob, M; Kramer, C; Dekant, W

    1992-07-01

    p-Aminophenol causes necrosis of the pars recta of the proximal tubules in rats, and its nephrotoxicity may be due to glutathione-dependent bioactivation reactions. We have investigated the hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S-yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3-(glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S-2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase.

  4. Comparative genomics of duplicate γ-glutamyl transferase genes in teleosts: medaka (Oryzias latipes), stickleback (Gasterosteus aculeatus), green spotted pufferfish (Tetraodon nigroviridis), fugu (Takifugu rubripes), and zebrafish (Danio rerio).

    PubMed

    Law, Sheran Hiu Wan; Redelings, Benjamin David; Kullman, Seth William

    2012-01-15

    The availability of multiple teleost (bony fish) genomes is providing unprecedented opportunities to understand the diversity and function of gene duplication events using comparative genomics. Here we examine multiple paralogous genes of γ-glutamyl transferase (GGT) in several distantly related teleost species including medaka, stickleback, green spotted pufferfish, fugu, and zebrafish. Through mining genome databases, we have identified multiple GGT orthologs. Duplicate (paralogous) GGT sequences for GGT1 (GGT1 a and b), GGTL1 (GGTL1 a and b), and GGTL3 (GGTL3 a and b) were identified for each species. Phylogenetic analysis suggests that GGTs are ancient proteins conserved across most metazoan phyla and those paralogous GGTs in teleosts likely arose from the serial 3R genome duplication events. A third GGTL1 gene (GGTL1c) was found in green spotted pufferfish; however, this gene is not present in medaka, stickleback, or fugu. Similarly, one or both paralogs of GGTL3 appear to have been lost in green spotted pufferfish, fugu, and zebrafish. Syntenic relationships were highly maintained between duplicated teleost chromosomes, among teleosts and across ray-finned (Actinopterygii) and lobe-finned (Sarcopterygii) species. To assess subfunction partitioning, six medaka GGT genes were cloned and assessed for developmental and tissue-specific expression. On the basis of these data, we propose a modification of the "duplication-degeneration-complementation" model of subfunction partitioning where quantitative differences rather than absolute differences in gene expression are observed between gene paralogs. Our results demonstrate that multiple GGT genes have been retained within teleost genomes. Questions remain, however, regarding the functional roles of multiple GGTs in these species. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.

  5. Discrimination of multilocus sequence typing-based Campylobacter jejuni subgroups by MALDI-TOF mass spectrometry.

    PubMed

    Zautner, Andreas Erich; Masanta, Wycliffe Omurwa; Tareen, Abdul Malik; Weig, Michael; Lugert, Raimond; Groß, Uwe; Bader, Oliver

    2013-11-07

    Campylobacter jejuni, the most common bacterial pathogen causing gastroenteritis, shows a wide genetic diversity. Previously, we demonstrated by the combination of multi locus sequence typing (MLST)-based UPGMA-clustering and analysis of 16 genetic markers that twelve different C. jejuni subgroups can be distinguished. Among these are two prominent subgroups. The first subgroup contains the majority of hyperinvasive strains and is characterized by a dimeric form of the chemotaxis-receptor Tlp7(m+c). The second has an extended amino acid metabolism and is characterized by the presence of a periplasmic asparaginase (ansB) and gamma-glutamyl-transpeptidase (ggt). Phyloproteomic principal component analysis (PCA) hierarchical clustering of MALDI-TOF based intact cell mass spectrometry (ICMS) spectra was able to group particular C. jejuni subgroups of phylogenetic related isolates in distinct clusters. Especially the aforementioned Tlp7(m+c)(+) and ansB+/ ggt+ subgroups could be discriminated by PCA. Overlay of ICMS spectra of all isolates led to the identification of characteristic biomarker ions for these specific C. jejuni subgroups. Thus, mass peak shifts can be used to identify the C. jejuni subgroup with an extended amino acid metabolism. Although the PCA hierarchical clustering of ICMS-spectra groups the tested isolates into a different order as compared to MLST-based UPGMA-clustering, the isolates of the indicator-groups form predominantly coherent clusters. These clusters reflect phenotypic aspects better than phylogenetic clustering, indicating that the genes corresponding to the biomarker ions are phylogenetically coupled to the tested marker genes. Thus, PCA clustering could be an additional tool for analyzing the relatedness of bacterial isolates.

  6. The genetic architecture of liver enzyme levels: GGT, ALT and AST.

    PubMed

    van Beek, Jenny H D A; de Moor, Marleen H M; de Geus, Eco J C; Lubke, Gitta H; Vink, Jacqueline M; Willemsen, Gonneke; Boomsma, Dorret I

    2013-07-01

    High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses (N = 8,371; age range 18-90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h(2) 60 %) and AST in both sexes (total h(2) 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus, the same genes influence liver enzyme levels across sex and age, but their relative contribution to the variation in GGT and ALT differs in males and females and for GGT across age. Given adequate sample sizes these results suggest that genome-wide association studies may result in the detection of new susceptibility loci for liver enzyme levels when pooling results over sex and age.

  7. Obesity, albuminuria, and gamma-glutamyl transferase predict incidence of hypertension in indigenous Australians in rural and remote communities in northern Australia.

    PubMed

    Li, Ming; McDermott, Robyn

    2015-04-01

    To describe the incidence of hypertension in a cohort of Australian Aboriginal and Torres Strait Islanders. A follow-up study conducted among 1831 indigenous population aged 15 years and over without hypertension at baseline from 19 communities in North Queensland during 1997-2008. Main measurements included baseline and follow-up weight, waist circumference, blood pressure, fasting glucose, lipids (triglycerides and cholesterol), gamma-glutamyl transferase, urinary albumin creatinine ratio, self-reported tobacco smoking, alcohol intake and physical activity. Hundred cases of hypertension developed over 2633.4 person-years giving a crude incidence of hypertension of 22.6 (16.2-31.4) per 1000 person-years in females and 60.0 (47.1-76.6) per 1000 person-years for males. Age standardized overall incidence was 51.9 per 1000 person-years. Aboriginal participants were twice as likely as Torres Strait Islanders to develop hypertension, which increased with age. Obesity (BMI >30) strongly predicted incident hypertension independently of age or sex (adjusted hazard ratio 2.9, 95% confidence interval 1.9-4.8). Albuminuria and elevated gamma-glutamyl transferase increased the risk of hypertension (adjusted hazard ratio 1.4-1.7) in this population. Incidence of hypertension in indigenous Australian adults is nearly double than that of the general Australian population. High background prevalence of obesity, diabetes and albuminuria contributes to this excess. As well as early detection and management of high blood pressure, albuminuria and diabetes in primary care settings, attention should be equally focused on community-level prevention and management of obesity.

  8. [Metabolism of rat liver in the electrostatic field and in the faraday cage before and after hepatectomy (author's transl)].

    PubMed

    Klingenberg, H G; Möse, J R; Fischer, G; Porta, J; Sadjak, A

    1975-10-01

    Investigations were performed with the aim of establishing the influence of various environmental conditions (such as steady field conditions, climatized laboratories, Faraday's cage) on a number of enzymic activities in the rat (including glutamic oxaloacetic tic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase), as well as the serum concentrations of triglycerides, the oxygen consumption of hepatic parenchyma cells, and the influence on the incorporation of 3H-thymidine (following partial hepatectomy). In the steady field, the activities of the cytoplasmic enzymes (GOT, GPT, LDH) were higher then under Faraday conditions. The same applies both to the hepatic oxygen consumption and to the neutral fat serum levels. The control values always remained within the range of the results obtained under steady field or Faraday conditions. In the structure-linked enzymes (gamma-glutamyl transpeptidase, acid phosphatase) the results were not uniform. Following partial hepatectomy, and under steady field conditions, the serum triglyceride concentrations showed a less pronounced drop than they did in the controls. Under selected environmental conditions, the results obtained lie within the physiological range. The present findings, therefore, do not permit definite conclusions to be drawn on favourable or unfavourable effects exerted by the different types of electroclimates.

  9. Role of glutathione S-transferase Pi in cisplatin-induced nephrotoxicity.

    PubMed

    Townsend, Danyelle M; Tew, Kenneth D; He, Lin; King, Jarrod B; Hanigan, Marie H

    2009-02-01

    One of the dose-limiting toxicities of cisplatin is nephrotoxicity. Renal toxicity is localized to quiescent proximal tubule cells, where the formation of DNA-adducts cannot account for the dose-limiting toxicity. Our earlier results have shown that a glutathione conjugate of cisplatin is metabolized to a nephrotoxicant via gamma-glutamyl transpeptidase (GGT) and a cysteine S-conjugate beta-lyase. The present study was designed to evaluate the potential role of glutathione S-transferase Pi (GSTP) in the initial steps of the bioactivation of cisplatin. Wild-type mice and mice deficient in both murine GSTP genes (GstP1/P2) were treated with cisplatin. Toxicity in both male and female mice was evaluated 5 days after treatment and renal damage was most severe in wild-type male mice. Wild-type males have approximately 10-fold higher levels of GSTP expression in the liver than females, suggesting that hepatic GSTP in the wild-type males contributed to the formation of the nephrotoxic platinum-glutathione conjugate. In GstP1/P2 null mice the gender difference in toxicity was eliminated. Our data show that GSTP expression is a determinant in cisplatin-induced nephrotoxicity and its levels contribute to sex-dependent differences.

  10. A vegetarian diet does not protect against nonalcoholic fatty liver disease (NAFLD): A cross-sectional study between Buddhist priests and the general population.

    PubMed

    Choi, Sung Hun; Oh, Dong Jun; Kwon, Ki Hwan; Lee, Jun Kyu; Koh, Moon Soo; Lee, Jin Ho; Kang, Hyoun Woo

    2015-07-01

    There is limited data that supports a role for a vegetarian diet in nonalcoholic fatty liver disease (NAFLD). The aim of this study is to evaluate the relationship between vegetarian diets and NAFLD, considering metabolic syndrome and obesity. This is a cross-sectional, retrospective study comparing the prevalence of NAFLD of 615 Buddhist priests and age-, sex-, Body mass index (BMI)-and presence/absence of metabolic syndrome-matched controls who underwent routine health checkups in a health promotion center. Diagnosis and severity of NAFLD was determined based on ultrasonographic findings. The prevalence of NAFLD was not statistically significantly different between the Buddhist priests and the general population (29.9% vs. 25.05%, p=0.055). The Buddhist priest group had higher serum albumin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum triglyceride levels and lower serum total bilirubin, serum fasting glucose, and serum high density lipoprotein (HDL) levels than the general population group. In univariate analysis and multivariate analysis, NAFLD was associated with old age, male gender, increased BMI, increased waist circumference, metabolic syndrome, high albumin, high glucose, high AST, high ALT, high gamma glutamyl transpeptidase (GGT), high triglycerides, low HDL, high low density lipoprotein (LDL), and high total cholesterol. The vegetarian diet does not protect against NAFLD.

  11. Extreme furfural tolerance of a soil bacterium Enterobacter cloacae GGT036.

    PubMed

    Choi, Sun Young; Gong, Gyeongtaek; Park, Hong-Sil; Um, Youngsoon; Sim, Sang Jun; Woo, Han Min

    2015-01-10

    Detoxification process of cellular inhibitors including furfural is essential for production of bio-based chemicals from lignocellulosic biomass. Here we isolated an extreme furfural-tolerant bacterium Enterobacter cloacae GGT036 from soil sample collected in Mt. Gwanak, Republic of Korea. Among isolated bacteria, only E. cloacae GGT036 showed cell growth with 35 mM furfural under aerobic culture. Compared to the maximal half inhibitory concentration (IC50) of well-known industrial strains Escherichia coli (24.9 mM furfural) and Corynebacterium glutamicum (10 mM furfural) based on the cell density, IC50 of E. cloacae GGT036 (47.7 mM) was significantly higher after 24 h, compared to E. coli and C. glutamicum. Since bacterial cell growth was exponentially inhibited depending on linearly increased furfural concentrations in the medium, we concluded that E. cloacae GGT036 is an extreme furfural-tolerant bacterium. Recently, the complete genome sequence of E. cloacae GGT036 was announced and this could provide an insight for engineering of E. cloacae GGT036 itself or other industrially relevant bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. In situ, dual-mode monitoring of organ-on-a-chip with smartphone-based fluorescence microscope.

    PubMed

    Cho, Soohee; Islas-Robles, Argel; Nicolini, Ariana M; Monks, Terrence J; Yoon, Jeong-Yeol

    2016-12-15

    The use of organ-on-a-chip (OOC) platforms enables improved simulation of the human kidney's response to nephrotoxic drugs. The standard method of analyzing nephrotoxicity from existing OOC has majorly consisted of invasively collecting samples (cells, lysates, media, etc.) from an OOC. Such disruptive analyses potentiate contamination, disrupt the replicated in vivo environment, and require expertize to execute. Moreover, traditional analyses, including immunofluorescence microscopy, immunoblot, and microplate immunoassay are essentially not in situ and require substantial time, resources, and costs. In the present work, the incorporation of fluorescence nanoparticle immunocapture/immunoagglutination assay into an OOC enabled dual-mode monitoring of drug-induced nephrotoxicity in situ. A smartphone-based fluorescence microscope was fabricated as a handheld in situ monitoring device attached to an OOC. Both the presence of γ-glutamyl transpeptidase (GGT) on the apical brush-border membrane of 786-O proximal tubule cells within the OOC surface, and the release of GGT to the outflow of the OOC were evaluated with the fluorescence scatter detection of captured and immunoagglutinated anti-GGT conjugated nanoparticles. This dual-mode assay method provides a novel groundbreaking tool to enable the internal and external in situ monitoring of the OOC, which may be integrated into any existing OOCs to facilitate their subsequent analyses. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. A large‐scale, multicentre, double‐blind trial of ursodeoxycholic acid in patients with chronic hepatitis C

    PubMed Central

    Omata, Masao; Yoshida, Haruhiko; Toyota, Joji; Tomita, Eiichi; Nishiguchi, Shuhei; Hayashi, Norio; Iino, Shiro; Makino, Isao; Okita, Kiwamu; Toda, Gotaro; Tanikawa, Kyuichi; Kumada, Hiromitsu

    2007-01-01

    Background Combined pegylated interferon and ribavirin has improved chronic hepatitis C (CH‐C) therapy; however, sustained virological response is achieved in only about half of the patients with a 1b genotype infection. We assessed oral ursodeoxycholic acid (UDCA) on serum biomarkers as a possible treatment for interferon non‐responders. Methods CH‐C patients with elevated alanine aminotransferase (ALT) were assigned randomly to 150 (n = 199), 600 (n = 200) or 900 mg/day (n = 197) UDCA intake for 24 weeks. Changes in ALT, aspartate aminotransferase (AST) and gamma‐glutamyl transpeptidase (GGT) were assessed. This study is registered at ClinicalTrial.gov, identifier NCT00200343. Results ALT, AST and GGT decreased at week 4 and then remained constant during drug administration. The median changes (150, 600 and 900 mg/day, respectively) were: ALT, −15.3, −29.2 and −36.2%; AST, −13.6, −25.0 and −29.8%; GGT, −22.4, −41.0 and −50.0%. These biomarkers decreased significantly less in the 150 mg/day than in the other two groups. Although changes in ALT and AST did not differ between the 600 and 900 mg/day groups, GGT was significantly lower in the 900 mg/day group. In subgroup analysis, ALT decreased significantly in the 900 mg/day group when the baseline GGT exceeded 80 IU/l. Serum HCV‐RNA did not change in any group. Adverse effects were reported by 19.1% of the patients, with no differences between groups. Conclusions A 600 mg/day UDCA dose was optimal to decrease ALT and AST levels in CH‐C patients. The 900 mg/day dose decreased GGT levels further, and may be preferable in patients with prevailing biliary injuries. PMID:17573387

  14. Phosphatidylethanol Levels Are Elevated and Correlate Strongly with AUDIT Scores in Young Adult Binge Drinkers.

    PubMed

    Piano, Mariann R; Tiwari, Stephanie; Nevoral, Lauren; Phillips, Shane A

    2015-09-01

    To compare levels of phosphatidylethanol (PEth) to self-reported alcohol intake among young adult binge drinkers (18-30 years). Abstainers (n = 23), moderate (n = 22), and binge drinkers (n = 58) completed an alcohol consumption questionnaire and the AUDIT. PEth was measured in whole blood and dried blood spots via high-performance liquid chromatography with tandem mass spectrometry. Also measured was mean corpuscular volume (MCV) and gamma glutamyl transpeptidase (GGT). Most subjects were female (65%) and Caucasian (73%). Among binge drinkers, past-month average number of binge episodes was 7.2 ± 4; average duration of binge drinking behavior was 4.3 ± 3 years. AUDIT scores and PEth levels (ng/ml) in whole blood or dried blood spots were significantly (P < 0.001) greater in binge drinkers (13 ± 4, 186 ± 170, and 65 ± 53, respectively) compared to moderate drinkers (6 ± 3, 24 ± 29, and 11 ± 13, respectively) and abstainers (0.6 ± 0.89, 0, and 0, respectively). No differences were found in MCV and GGT among groups. There were significant correlations between whole blood and dried blood spot PEth levels and AUDIT scores (Spearman's r = 0.745 and 0.738, P < 0.0001, respectively), and whole blood and dried blood spot PEth levels were significantly correlated (0.899, P < 0.0001). PEth levels measured in whole blood and dried blood spots were significantly greater in binge drinkers compared to abstainers and moderate drinkers, and these levels were positively correlated with AUDIT scores. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  15. [Clinical and genetic study of an infant with Alagille syndrome: identification of a novel chromosomal interstitial deletion including JAG1 gene].

    PubMed

    Li, Hua; Liu, Jia-Jia; Deng, Mei; Guo, Li; Cheng, Ying; Song, Yuan-Zong

    2017-10-01

    Alagille syndrome (ALGS) is an autosomal dominant disease affecting multiple systems including the liver, heart, skeleton, eyes, kidneys and face. This paper reports the clinical and genetic features of an infant with this disease. A 3-month-and-10-day-old female infant was referred to the hospital with jaundiced skin and sclera for 3 months. Physical examination revealed wide forehead and micromandible. A systolic murmur of grade 3-4/6 was heard between the 2th and 3th intercostal spaces on the left side of the sternum. The abdomen was distended, and the liver palpable 3 cm under the right subcostal margin with a medium texture. Serum biochemistry analysis revealed abnormal liver function indices, with markedly elevated bilirubin (predominantly direct bilirubin), total bile acids (TBA) and gamma-glutamyl transpeptidase (GGT). Atrial septal defect and pulmonary stenosis were detected on echocardiography. Next generation sequencing detected entire deletion of the JAG1 gene, and then chromosomal microarray analysis revealed a novel interstitial deletion of 3.0 Mb in size on chr20p12.3p12.2, involving JAG1 gene. The child had special facial features, heart malformations, and cholestasis, and based on the genetic findings, ALGS was definitively diagnosed. Thereafter, symptomatic and supportive treatment was introduced. Thus far, the infant had been followed up till his age of 11 months. The hyperbilirubinemia got improved, but GGT and TBA were persistently elevated, and the long-term outcome needs to be observed. This study extended the JAG1 mutation spectrum, and provided laboratory evidences for the diagnosis and treatment of the patient, and for the genetic counseling and prenatal diagnosis in the family.

  16. Causal mediation analysis with multiple mediators.

    PubMed

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  17. Association of canalicular membrane enzymes with bile acid micelles and lipid aggregates in human and rat bile.

    PubMed

    Accatino, L; Pizarro, M; Solís, N; Koenig, C S

    1995-01-18

    This study was undertaken to gain insights into the characteristics of the polymolecular association between canalicular membrane enzymes, bile acids, cholesterol and phospholipids in bile and into the celular mechanisms whereby the enzymes are secreted into bile. With this purpose, we studied the distribution of bile acids, cholesterol, phospholipids, proteins and representative canalicular membrane enzymes (alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase), which can be considered specific marker constituents, in bile fractions enriched in phospholipid-cholesterol lamellar structures (multilamellar and unilamellar vesicles) and bile acid-mixed micelles. These fractions were isolated by ultracentrifugation from human hepatic bile, normal rat bile and bile of rats treated with diosgenin, a steroid that induces a marked increase in biliary cholesterol secretion, and were characterized by density, lipid composition and transmission electron microscopy. These studies demonstrate that alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase are secreted into both human and rat bile where they are preferentially associated with bile acid-mixed micelles, suggesting a role for bile acids in both release of these enzymes and lipids from the canalicular membrane and solubilization in bile. In addition, heterogeneous association of these enzymes with nonmicellar, lamellar structures in human and rat bile is consistent with the hypothesis that processes independent of the detergent effects of bile acids might also result in the release of specific intrinsic membrane proteins into bile.

  18. Nigella sativa (black cumin) ameliorates potassium bromate-induced early events of carcinogenesis: diminution of oxidative stress.

    PubMed

    Khan, Naghma; Sharma, Sonia; Sultana, Sarwat

    2003-04-01

    Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this paper, we report the chemopreventive effect of Nigella sativa (black cumin) on KBrO3-mediated renal oxidative stress, toxicity and tumor promotion response in rats. KBrO3 (125 mg/kg body weight, intraperitoneally) enhances lipid peroxidation, gamma-glutamyl transpeptidase, hydrogen peroxide and xanthine oxidase with reduction in the activities of renal antioxidant enzymes and renal glutathione content. A marked increase in blood urea nitrogen and serum creatinine has also been observed. KBrO3 treatment also enhances ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into renal DNA. Prophylaxis of rats orally with Nigella sativa extract (50 mg/kg body weight and 100 mg/kg body weight) resulted in a significant decrease in renal microsomal lipid peroxidation (P < 0.001), gamma-glutamyl transpeptidase (P < 0.001), H2O2 (P < 0.001) and xanthine oxidase (P < 0.05). There was significant recovery of renal glutathione content (P < 0.01) and antioxidant enzymes (P < 0.001). There was also reversal in the enhancement of blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Data suggest that Nigella sativa is a potent chemopreventive agent and may suppress KBrO3-mediated renal oxidative stress, toxicity and tumour promotion response in rats.

  19. Effects of Synthetic Androgens on Liver Function Using the Rabbit as a Model*†

    PubMed Central

    Hild, Sheri Ann; Attardi, Barbara J.; Koduri, Sailaja; Till, Bruce A.; Reel, Jerry R.

    2010-01-01

    The objective of this study was to determine if the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0–13 with 17α-methyltestosterone (MT), as a positive control, and testosterone (T), as a negative control, to validate this model. Synthetic androgens tested were: 7α-methyl-19-nortestosterone (MENT), dimethandrolone-undecanoate (DMAU), and 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7 and 14, were determined. As expected, T (10 mg/kg/day) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/day) increased BSP retention, and AST, ALT, GGT, and SDH levels indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/day), increased BSP retention, and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11β-MNTDC at 10 mg/kg/day did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/day. For the androgens that exhibited liver toxicity at 10 mg/kg/day (MT, DMAU, and MENT), a no observed effect level (NOEL) of 1 mg/kg/day was established. Overall ranking of the synthetic androgens from most to least hepatotoxic based on %BSP retention was: MT ≫ DMAU > MENT > 11β-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury. PMID:20378929

  20. Antimicrobial Activities of Isothiocyanates Against Campylobacter jejuni Isolates

    PubMed Central

    Dufour, Virginie; Alazzam, Bachar; Ermel, Gwennola; Thepaut, Marion; Rossero, Albert; Tresse, Odile; Baysse, Christine

    2012-01-01

    Food-borne human infection with Campylobacter jejuni is a medical concern in both industrialized and developing countries. Efficient eradication of C. jejuni reservoirs within live animals and processed foods is limited by the development of antimicrobial resistances and by practical problems related to the use of conventional antibiotics in food processes. We have investigated the bacteriostatic and bactericidal activities of two phytochemicals, allyl-isothiocyanate (AITC), and benzyl isothiocyanate (BITC), against 24 C. jejuni isolates from chicken feces, human infections, and contaminated foods, as well as two reference strains NCTC11168 and 81-176. AITC and BITC displayed a potent antibacterial activity against C. jejuni. BITC showed a higher overall antibacterial effect (MIC of 1.25–5 μg mL−1) compared to AITC (MIC of 50–200 μg mL−1). Both compounds are bactericidal rather than bacteriostatic. The sensitivity levels of C. jejuni isolates against isothiocyanates were neither correlated with the presence of a GGT (γ-Glutamyl Transpeptidase) encoding gene in the genome, with antibiotic resistance nor with the origin of the biological sample. However the ggt mutant of C. jejuni 81-176 displayed a decreased survival rate compared to wild-type when exposed to ITC. This work determined the MIC of two ITC against a panel of C. jejuni isolates, showed that both compounds are bactericidal rather than bacteriostatic, and highlighted the role of GGT enzyme in the survival rate of C. jejuni exposed to ITC. PMID:22919644

  1. Pesticide risk assessment: A study on inhalation and dermal exposure to 2,4-D and paraquat among Malaysian paddy farmers.

    PubMed

    Baharuddin, Mohd Rafee B; Sahid, Ismail B; Noor, Mohamad Azhar B Mohd; Sulaiman, Norela; Othman, Fadzil

    2011-01-01

    A cross-section analytical study was conducted to evaluate the risk of pesticide exposure to those applying the Class II pesticides 2,4-D and paraquat in the paddy-growing areas of Kerian, Perak, Malaysia. It investigated the influence of weather on exposure as well as documented health problems commonly related to pesticide exposure. Potential inhalation and dermal exposure for 140 paddy farmers (handlers of pesticides) were assessed. Results showed that while temperature and humidity affected exposure, windspeed had the strongest impact on pesticide exposure via inhalation. However, the degree of exposure to both herbicides via inhalation was below the permissible exposure limits set by United States National Institute of Occupational Safety and Health (NIOSH). Dermal Exposure Assessment Method (DREAM) readings showed that dermal exposure with manual spraying ranged from moderate to high. With motorized sprayers, however, the level of dermal exposure ranged from low to moderate. Dermal exposure was significantly negatively correlated with the usage of protective clothing. Various types of deleterious health effects were detected among users of manual knapsack sprayers. Long-term spraying activities were positively correlated with increasing levels of the gamma-glutamyl transpeptidase (GGT) liver enzyme. The type of spraying equipment, usage of proper protective clothing and adherence to correct spraying practices were found to be the most important factors influencing the degree of pesticide exposure among those applying pesticides.

  2. The Role of Ischemia Modified Albumin as a Biomarker in Patients with Chronic Liver Disease.

    PubMed

    Kumar, Prashanth Ashok; Subramanian, Kavitha

    2016-03-01

    Chronic Liver Disease (CLD) is characterised by gradual destruction of liver tissue over time. Ischemia Modified Albumin (IMA) is an upcoming biomarker shown to be elevated in conditions associated with ischemia and oxidative stress. Albumin levels are greatly reduced in patients with CLD and studying its alterations will provide essential information regarding the molecular changes occurring to it. The study aims to estimate IMA and IMA/Albumin ratio in patients with CLD and to correlate it with parameters assessing liver function and the Model for End Stage Liver Disease (MELD) score. The study consisted of 43 CLD patients as test subjects and 28 apparently healthy individuals as controls. Multiple parameters assessing liver function like albumin, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), Gamma Glutamyl Transpeptidase (GGT), alkaline phosphatase (ALP), Prothrombin Time (PT) INR and creatinine were estimated and the MELD score calculated. Serum IMA expressed as Absorbance Units (ABSU) was estimated using the Albumin Cobalt Binding test (ABT). Student's t-test and correlation coefficient was used for statistical analysis. Serum IMA was significantly higher in CLD patients (0.5320 ± 0.1677) as compared to the control group (0.3203 ± 0.1257) with a p-value of <0.0001. The IMA/Albumin ratio was also significantly higher (0.2035 ± 0.0970) in patients with CLD compared to control group (0.0714 ± 0.0283) with a p-value of <0.0001. IMA has a negative correlation with albumin. The IMA/Albumin ratio shows positive correlation with MELD score, bilirubin and ALP. There was no correlation with ALT, AST, GGT and PT INR. Decreased serum albumin correlates with increase in IMA in CLD could indicate a qualitative change and not merely a quantitative reduction of albumin. IMA can serve as a biomarker to assess the disease severity and prognosis of CLD patients.

  3. Age-dependent systemic DNA damage in early Type 2 Diabetes mellitus.

    PubMed

    Rogulj, Dinko; El Aklouk, Ismail; Konjevoda, Paško; Ljubić, Spomenka; Pibernik Okanović, Mirjana; Barbir, Ante; Luburić, Marijana; Radman, Maja; Budinski, Ninoslav; Vučić Lovrenčić, Marijana

    2017-01-01

    Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM. Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, gamma-glutamyl transpeptidase (GGT), uric acid, C-reactive protein (CRP), total leukocyte/neutrophil count, and urinary 8-hidroxy-deoxyguanosine (u-8-OHdG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications. BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-OHdG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Higher 8-OHdG in older subjects with T2DM suggests that both aging process and diabetes could contribute to the development of DNA damage. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

  4. Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study.

    PubMed

    Kokaze, Akatsuki; Yoshida, Masao; Ishikawa, Mamoru; Matsunaga, Naomi; Karita, Kanae; Ochiai, Hirotaka; Shirasawa, Takako; Nanri, Hinako; Mitsui, Kiyomi; Hoshimo, Hiromi; Takashima, Yutaka

    2016-06-04

    Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees. A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on elevated levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum gamma-glutamyl transpeptidase (GGT) was then conducted. For men with Mt5178C, after adjustment for age, body mass index, alcohol consumption, habitual smoking, green tea consumption, antihypertensive treatment, and antidiabetic treatment, elevated levels of serum AST, as defined as ≥30 U/L; those of serum ALT, as defined as ≥25 U/L; or those of serum GGT, as defined as ≥60 or >51 U/L, may depend on coffee consumption (P for trend = 0.013, P for trend <0.001, P for trend = 0.002, and P for trend <0.001, respectively). On the other hand, no significant joint effects of Mt5178A genotype and coffee consumption on elevated levels of serum liver enzymes were observed. The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.

  5. Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

    PubMed

    Williams, Kathryn H; Sullivan, David R; Nicholson, Geoffrey C; George, Jacob; Jenkins, Alicia J; Januszewski, Andrzej S; Gebski, Val J; Manning, Patrick; Tan, Yong Mong; Donoghoe, Mark W; Ehnholm, Christian; Young, Simon; O'Brien, Richard; Buizen, Luke; Twigg, Stephen M; Keech, Anthony C

    2016-05-01

    Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5years. Over 5years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001. Conversely, GGT >70U/L, compared with GGT ≤70U/L, had HR 1.82 (1.48-2.24), p<0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Influence of hepatic load from far-off dry period to early postpartum period on the first postpartum ovulation and accompanying subsequent fertility in dairy cows.

    PubMed

    Kawashima, Chiho; Ito, Nozomi; Nagashima, Shuntarou; Matsui, Motozumi; Sawada, Kumiko; Schweigert, Florian J; Miyamoto, Akio; Kida, Katsuya

    2016-06-17

    The aim of the present study was to investigate nutritional and metabolic parameters during the dry and early postpartum periods of ovulatory and anovulatory cows, as well as their postpartum reproductive performance. Blood samples from 20 multiparous Holstein cows were collected once a week from the far-off dry period to 3 weeks postpartum. Early postpartum (0-3 weeks) ovulation was confirmed using plasma progesterone concentration profiles, and cows were considered ovulatory if they had resumed luteal activity by this point (n = 9), whereas cows that had not were considered anovulatory (n = 11). Data from the ovulatory and anovulatory cows were analyzed separately for the far-off dry period (7-4 weeks prepartum), the close-up dry period (3-1 weeks prepartum), and the early postpartum period (0-3 weeks). Serum gamma-glutamyl transpeptidase activity (far-off, P = 0.065; close-up, P = 0.051; and early postpartum, P = 0.030) and aspartate aminotransferase (close-up, P = 0.050 and early postpartum, P = 0.087) activities were higher in anovulatory than in ovulatory cows. The days open period was longer (P = 0.019) in anovulatory than in ovulatory cows, and the number of artificial inseminations per conception (P = 0.025) was greater. In conclusion, we found that continuously high gamma-glutamyl transpeptidase activities in serum, which may be induced by liver disorders, prevent subsequent ovulation and affect subsequent fertility, even if cows obtain sufficient ovulation-related energy and β-carotene.

  7. Health problems in adolescents with alcohol use disorders: self-report, liver injury, and physical examination findings and correlates.

    PubMed

    Clark, D B; Lynch, K G; Donovan, J E; Block, G D

    2001-09-01

    Although adolescent alcohol consumption has been found to be positively correlated with self-reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self-reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated. The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or alcohol abuse (n = 57) and reference adolescents without AUDs recruited from community sources (n = 131). The assessment of health status included self-reported health problems in 15 areas; serum liver enzyme assays, including gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire. Adolescent AUDs were associated with more self-reported health problems, higher gamma-glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self-reported health problems, mediated the relationship between AUDs and self-reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities. These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self-reported health problems were probably best understood, in this context, as a negative emotionality manifestation.

  8. Circulating gamma-glutamyltransferase fractions in cirrhosis.

    PubMed

    Elawdi, Hassan A; Franzini, Maria; Paolicchi, Aldo; Emdin, Michele; Fornaciari, Irene; Fierabracci, Vanna; De Simone, Paolo; Carrai, Paola; Filipponi, Franco

    2014-08-01

    Four gamma-gultamyltransferases (GGT) fractions (b-, m-, s-, and f-GGT) have been identified in human plasma and their concentrations and ratios vary in different pathological conditions. To assess the behaviour of fractional GGT in cirrhotic patients evaluated for liver transplantation. This was a single-centre, cross-sectional study; GGT fractions were determined by gel-filtration chromatography. 264 cirrhotic patients (215 males; median age 54.5 years) were included and compared against a group of 200 healthy individuals (100 males; median age 41.5). Median (25th-75th percentile) total and fractional GGT were higher in cirrhotics, with s-GGT showing the greatest increase [36.6 U/L (21.0-81.4) vs. 5.6 U/L (3.2-10.2), P<0.0001], while the median b-GGT/s-GGT ratio was lower in cirrhotics than in healthy controls [0.06 (0.04-0.10)] vs. 0.28 (0.20-0.40), P<0.0001]. The ratio showed higher diagnostic accuracy (ROC-AUC, 95% CI: 0.951, 0.927-0.969) then either s-GGT (0.924, 0.897-0.947; P<0.05) or total GGT (0.900, 0.869-0.925; P<0.001). The diagnostic accuracy of the ratio was maintained (0.940, 0.907-0.963) in cirrhotic patients (n=113) with total GGT values within the reference range. The s-GGT fraction consisted of two components, with one (s2-GGT) showing a significant positive correlation with serum aspartate aminotransferases, alanine aminotransferase, lactate dehydrogenases (LDH), alkaline phosphatases and bilirubin, and negative with albumin. The b-GGT fraction showed a positive correlation with albumin, fibrinogen, and platelet counts, and negative with international normalized ratio, bilirubin and LDH. The ratio performs as a sensitive biomarker of the liver parenchymal rearrangement, irrespective of aetiology of cirrhosis and presence of hepatocellular carcinoma, even in patients with total GGT values within the reference range. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Excessive drinking--brief intervention by a primary health care nurse. A randomized controlled trial.

    PubMed

    Tomson, Y; Romelsjö, A; Aberg, H

    1998-09-01

    To evaluate the effect of a nurse-conducted intervention on excessive drinkers. Randomized, controlled trial. Vårby Health Centre, Stockholm. The intervention group visited a nurse three times during a 12-month period. The controls met once with a general practitioner (GP). Patients were recruited at a health screening on the basis of a raised gamma-glutamyl transferase (GGT). Of 2338 subjects, aged 25-54 years, 222 had a screening GGT of > or = 0.9 mukat/l. 100 were randomized to the treatment and 122 to the control group. GGT, self-reported alcohol consumption (g/week), sickness allowance and use of health care. After 2 years a reduction of GGT from 1.52 to 1.21 mukat/l (p = 0.02) had occurred in the treatment group. The controls increased their mean level of GGT from 1.75 to 2.16 mukat/l. Mean weekly alcohol consumption in the intervention group was reduced from 337 to 228 g/week (p = 0.02). The controls did not quantify their alcohol consumption initially, but reported a reduced weekly consumption at follow-up. The intervention had an impact on GGT and self-reported consumption. The controls also reported decreased consumption possibly because their appointment with the GP functioned as a very brief intervention.

  10. Early Biochemical Effects of an Organic Mercury Fungicide on Infants: ``Dose Makes the Poison''

    NASA Astrophysics Data System (ADS)

    Gotelli, Carlos A.; Astolfi, Emilio; Cox, Christopher; Cernichiari, Elsa; Clarkson, Thomas W.

    1985-02-01

    Phenylmercury absorbed through the skin from contaminated diapers affected urinary excretion in infants in Buenos Aires. The effects were reversible and quantitatively related to the concentration of urinary mercury. Excretion of γ -glutamyl transpeptidase, an enzyme in the brush borders of renal tubular cells, increased in a dose-dependent manner when mercury excretion exceeded a ``threshold'' value. Urine volume also increased but at a higher threshold with respect to mercury. The results support the threshold concept of the systemic toxicity of metals. γ -Glutamyl transpeptidase is a useful and sensitive marker for preclinical effects of toxic metals.

  11. Gamma-glutamyltransferase fractions in human plasma and bile: characteristic and biogenesis.

    PubMed

    Fornaciari, Irene; Fierabracci, Vanna; Corti, Alessandro; Aziz Elawadi, Hassan; Lorenzini, Evelina; Emdin, Michele; Paolicchi, Aldo; Franzini, Maria

    2014-01-01

    Total plasma gamma-glutamyltransferase (GGT) activity is a sensitive, non-specific marker of liver dysfunction. Four GGT fractions (b-, m-, s-, f-GGT) were described in plasma and their differential specificity in the diagnosis of liver diseases was suggested. Nevertheless fractional GGT properties have not been investigated yet. The aim of this study was to characterize the molecular nature of fractional GGT in both human plasma and bile. Plasma was obtained from healthy volunteers; whereas bile was collected from patients undergoing liver transplantation. Molecular weight (MW), density, distribution by centrifugal sedimentation and sensitivity to both detergent (deoxycholic acid) and protease (papain) were evaluated. A partial purification of b-GGT was obtained by ultracentrifugation. Plasma b-GGT fraction showed a MW of 2000 kDa and a density between 1.063-1.210 g/ml. Detergent converted b-GGT into s-GGT, whereas papain alone did not produce any effect. Plasma m-GGT and s-GGT showed a MW of 1,000 and 200 kDa, and densities between 1.006-1.063 g/ml and 1.063-1.210 g/ml respectively. Both fractions were unaffected by deoxycholic acid, while GGT activity was recovered into f-GGT peak after papain treatment. Plasma f-GGT showed a MW of 70 kDa and a density higher than 1.21 g/ml. We identified only two chromatographic peaks, in bile, showing similar characteristics as plasma b- and f-GGT fractions. These evidences, together with centrifugal sedimentation properties and immunogold electronic microscopy data, indicate that b-GGT is constituted of membrane microvesicles in both bile and plasma, m-GGT and s-GGT might be constituted of bile-acid micelles, while f-GGT represents the free-soluble form of the enzyme.

  12. Association between gamma-glutamyltransferase and coronary artery calcification.

    PubMed

    Atar, Asli I; Yilmaz, Omer C; Akin, Kayihan; Selcoki, Yusuf; Er, Okan; Eryonucu, Beyhan

    2013-08-20

    The exact mechanisms behind the association between atherosclerosis and gamma-glutamyltransferase (GGT) are unclear. Coronary artery calcification (CAC) detected by computerized tomography is an important marker of atherosclerosis and its severity correlates with coronary plaque burden. The aim of this study was to investigate if serum GGT levels are associated with CAC in patients without known coronary heart disease (CHD) who had low-intermediate risk for CHD. Two hundred and seventy two patients who had low-intermediate risk for coronary artery disease were included in the study. Serum GGT levels were measured spectrophotometrically. CACS (Agatston method) were performed using a 64-slice computerized tomography scanner. The patients were grouped according to their GGT values in four quartiles. Patients in higher GGT quartiles had elevated CAC score (P<0.001). Patients in higher GGT quartiles were predominantly males (P<0.001) and were more likely to be smoking (P=0.004), and have elevated uric acid (P<0.001), fasting blood glucose (P<0.001), CRP levels (P=0.003) and 10-year total cardiovascular risk (P=0.007) and low HDL levels (P<0.001). Positive correlations were found between log GGT and CAC (r=0.233, P<0.001). In the multivariate analysis GGT, age, smoking and serum uric acid levels appeared as independent factors predictive of presence of CAC. We demonstrated a significant correlation between serum GGT levels and CAC and CHD risk factors. Serum GGT level was an independent marker of CAC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. A study on risk factors and diagnostic efficiency of posthepatectomy liver failure in the nonobstructive jaundice.

    PubMed

    Wang, He; Lu, Shi-Chun; He, Lei; Dong, Jia-Hong

    2018-02-01

    Liver failure remains as the most common complication and cause of death after hepatectomy, and continues to be a challenge for doctors.t test and χ test were used for single factor analysis of data-related variables, then results were introduced into the model to undergo the multiple factors logistic regression analysis. Pearson correlation analysis was performed for related postoperative indexes, and a diagnostic evaluation was performed using the receiver operating characteristic (ROC) of postoperative indexes.Differences in age, body mass index (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time, cumulative portal vein occlusion time, intraoperative blood volume, residual liver volume (RLV)/entire live rvolume, ascites volume at postoperative day (POD)3, supplemental albumin amount at POD3, hospitalization time after operation, and the prothrombin activity (PTA) were statistically significant. Furthermore, there were significant differences in total bilirubin and the supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin amounts, ascites volume at POD3, and their combined diagnosis were performed, which had diagnostic value for postoperative liver failure (area under the curve (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903).Preoperative total bilirubin level and the supplemental albumin amount at POD3 were independent risk factors. PTA can be used as the index of postoperative liver failure, and the combined diagnosis of the indexes can improve the early prediction of postoperative liver failure.

  14. Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

    PubMed Central

    Milton Prabu, S.; Muthumani, M.; Shagirtha, K.

    2012-01-01

    The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats. PMID:23961183

  15. Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats.

    PubMed

    Milton Prabu, S; Muthumani, M; Shagirtha, K

    2012-04-01

    The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.

  16. Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

    PubMed

    Müller, Liz Girardi; Pase, Camila Simonetti; Reckziegel, Patrícia; Barcelos, Raquel C S; Boufleur, Nardeli; Prado, Ana Cristina P; Fett, Roseane; Block, Jane Mara; Pavanato, Maria Amália; Bauermann, Liliane F; da Rocha, João Batista Teixeira; Burger, Marilise Escobar

    2013-01-01

    The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption. Copyright © 2011 Elsevier GmbH. All rights reserved.

  17. Regulatory aspects of the glutamylation of methotrexate in cultured hepatoma cells

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

    Nimec, Z.; Galivan, J.

    1983-10-15

    The glutamylation of methotrexate has been evaluated in H35 hepatoma cells in vitro as a function of the conditions of culture. Glutamylation yields methotrexate polyglutamate with two to five additional glutamate residues and is a saturable process. The rate of glutamylation increases little above 10 microM extracellular methotrexate which corresponds to an intracellular concentration of approximately 4 microM. The rate of glutamylation measured over a 6-h period was stimulated by a reduction in cellular folates and prior incubation of the cells with insulin. Glutamylation was also more rapid in dividing cultures than in confluent cells. The combination of insulin inclusionmore » and folate reduction, which was additive, caused approximately a fourfold increase in the rate of glutamylation over control cells under the conditions tested. The maximal rate of methotrexate glutamylation, which was 100 nmol/g/h, occurred in folate-depleted, insulin-supplemented cells. Supplementing folate-depleted cells with reduced folate coenzymes caused the glutamylation to be reduced by more than 90%. In addition to showing that folates can modify the rates of methotrexate polyglutamate formation, data are presented suggesting that methotrexate polyglutamates can regulate their own synthesis. The consequences of the formation of these retained forms of methotrexate in H35 hepatoma cells and the effects of potential regulators of this process are discussed in terms of the glutamylation of folates in the cells and the chemotherapeutic effects of antifolates.« less

  18. Correlation between gamma glutamyltransferase fractions and bone quality.

    PubMed

    Franzini, M; Nesti, A; Panetta, D; Fierabracci, V; Marchetti, S; Parchi, P D; Caponi, L; Paolicchi, A; Musetti, V; Salvadori, P; Edmin, M; Pucci, A; Bonicoli, E; Scaglione, M; Piolanti, N

    Gamma-glutamyltransferase (GGT) has been recently identified as a bone-resorbing factor. The aim of this study was to investigate the association between plasma GGT fractions levels and bone quality. Plasma GGT fractions were analysed by gel-filtration chromatography. Bone quality was established quantitatively by two micro-CT derived microarchitectural parameters: the BV/TV (mineralised bone volume/total volume), and the SMI (structure model index) that describes the rod-like (low resistant) or plate-like (high-resistant) shape of bone trabeculae. We enrolled 93 patients hospitalised for elective total hip replacement (group Arthrosis, n=46) or for proximal femoral fracture (group Fracture, n=47). Patients within the first quartile of BV/TV (Q1, osteoporotic patients, n=6) showed higher levels of b-GGT fraction [median (min-max): 3.37 (1.42–6.81)] compared to patients with normal bone density (fourth quartile Q4, n=10; 1.40 (0.83–4.36); p=0.0393]. Also, according to SMI, b-GGT value was higher in the subgroup with bone fragility [Q1, n=8: 1.36 (0.43–4.36); Q4, n=8: 5.10 (1.4 –7.60); p=0.0117]. In conclusion, patients characterised by fragile bone structure showed specifically higher levels of plasma b-GGT activity thus suggesting fractional GGT analysis as a possible biomarker in the diagnosis of osteoporosis.

  19. Caenorhabditis elegans glutamylating enzymes function redundantly in male mating.

    PubMed

    Chawla, Daniel G; Shah, Ruchi V; Barth, Zachary K; Lee, Jessica D; Badecker, Katherine E; Naik, Anar; Brewster, Megan M; Salmon, Timothy P; Peel, Nina

    2016-09-15

    Microtubule glutamylation is an important modulator of microtubule function and has been implicated in the regulation of centriole stability, neuronal outgrowth and cilia motility. Glutamylation of the microtubules is catalyzed by a family of tubulin tyrosine ligase-like (TTLL) enzymes. Analysis of individual TTLL enzymes has led to an understanding of their specific functions, but how activities of the TTLL enzymes are coordinated to spatially and temporally regulate glutamylation remains relatively unexplored. We have undertaken an analysis of the glutamylating TTLL enzymes in C. elegans We find that although all five TTLL enzymes are expressed in the embryo and adult worm, loss of individual enzymes does not perturb microtubule function in embryonic cell divisions. Moreover, normal dye-filling, osmotic avoidance and male mating behavior indicate the presence of functional amphid cilia and male-specific neurons. A ttll-4(tm3310); ttll-11(tm4059); ttll-5(tm3360) triple mutant, however, shows reduced male mating efficiency due to a defect in the response step, suggesting that these three enzymes function redundantly, and that glutamylation is required for proper function of the male-specific neurons. © 2016. Published by The Company of Biologists Ltd.

  20. An Integrated Approach Combining Chemical Analysis and an In Vivo Bioassay to Assess the Estrogenic Potency of a Municipal Solid Waste Landfill Leachate in Qingdao

    PubMed Central

    Gong, Yufeng; Tian, Hua; Wang, Lijia; Yu, Suping; Ru, Shaoguo

    2014-01-01

    Various adverse effects related to landfill leachate have made leachates an important issue in past decades, and it has been demonstrated that landfill leachate is an important source of environmental estrogens. In this study, we employed chemical analysis of some already evaluated estrogenic substances, in combination with a bioassay using several specific biomarkers (e.g., plasma vitellogenin and sex steroids, enzyme activity of gonad gamma-glutamyl transpeptidase, and gonadosomatic index) to evaluate the estrogenic activities in outlets from different stages of the leachate treatment process. The results indicated that 5 environmental estrogens (4-t-octylphenol, bisphenol A, di-ethyl phthalate, di-n-butyl phthalate, and diethylhexyl phthalate) were detected by a gas chromatography-mass spectrometry, and the concentrations in leachate samples were 6153 ng/L, 3642 ng/L, 2139 ng/L, 5900 ng/L, and 9422 ng/L, respectively. Leachate (1∶200 diluted) induced the synthesis of plasma vitellogenin and led to decreased enzyme activity of gonad gamma-glutamyl transpeptidase and gonadosomatic index in male goldfish (Carassius auratus) after a 28-day exposure, while increased circulating 17β-estradiol level was also observed in males exposed to treated effluent. Although the target EEs were partially removed with removal rates varying from 87.2% to 99.77% by the “membrane bioreactor+reverse osmosis+aeration zeolite biofilter” treatment process, the treated effluent is still estrogenic to fish. The method combined chemical techniques with the responses of test organisms allowing us to identify the group of estrogen-like chemicals so that we were able to evaluate the overall estrogenic effects of a complex mixture, avoiding false negative assessments. PMID:24743634

  1. *NO and oxyradical metabolism in new cell lines of rat brain capillary endothelial cells forming the blood-brain barrier.

    PubMed

    Blasig, I E; Giese, H; Schroeter, M L; Sporbert, A; Utepbergenov, D I; Buchwalow, I B; Neubert, K; Schönfelder, G; Freyer, D; Schimke, I; Siems, W E; Paul, M; Haseloff, R F; Blasig, R

    2001-09-01

    To investigate the relevance of *NO and oxyradicals in the blood-brain barrier (BBB), differentiated and well-proliferating brain capillary endothelial cells (BCEC) are required. Therefore, rat BCEC (rBCEC) were transfected with immortalizing genes. The resulting lines exhibited endothelial characteristics (factor VIII, angiotensin-converting enzyme, high prostacyclin/thromboxane release rates) and BBB markers (gamma-glutamyl transpeptidase, alkaline phosphatase). The control line rBCEC2 (mock transfected) revealed fibroblastoid morphology, less factor VIII, reduced gamma-glutamyl transpeptidase, weak radical defence, low prostanoid metabolism, and limited proliferation. Lines transfected with immortalizing genes (especially rBCEC4, polyoma virus large T antigen) conserved primary properties: epitheloid morphology, subcultivation with high proliferation rate under pure culture conditions, and powerful defence against reactive oxygen species (Mn-, Cu/Zn-superoxide dismutase, catalase, glutathione peroxidase, glutathione) effectively controlling radical metabolism. Only 100 microM H2O2 overcame this defence and stimulated the formation of eicosanoids similarly as in primary cells. Some BBB markers were expressed to a lower degree; however, cocultivation with astrocytes intensified these markers (e.g., alkaline phosphatase) and paraendothelial tightness, indicating induction of BBB properties. Inducible NO synthase was induced by a cytokine plus lipopolysaccharide mixture in all lines and primary cells, resulting in *NO release. Comparing the cell lines obtained, rBCEC4 are stable immortalized and reveal the best conservation of properties from primary cells, including enzymes producing or decomposing reactive species. These cells can be subcultivated in large amounts and, hence, they are suitable to study the role of radical metabolism in the BBB and in the cerebral microvasculature. Copyright 2001 Academic Press.

  2. Role of APN and TNF-α in type 2 diabetes mellitus complicated by nonalcoholic fatty liver disease.

    PubMed

    Lin, X; Zhang, Z; Chen, J M; Xu, Y Y; Ye, H R; Cui, J; Fang, Y; Jin, Y; Zhu, D R; Yuan, L

    2015-04-10

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by non-excessive alcohol consumption and is the most common cause of elevated levels of serum liver enzymes. We examined changes in adiponectin (APN) and tumor necrosis factor-α (TNF-α) in type 2 diabetes mellitus (T2DM) complicated by NAFLD and their relationships with insulin resistance (IR). Forty-two T2DM, 39 NAFLD, and 45 T2DM complicated with NAFLD (complicated group) patients were enrolled in this study. Body mass index, fasting blood plasma glucose (FPG), fasting insulin, triglyceride (TG), alanine aminotransferase, gamma-glutamyl transpeptidase, APN, TNF-α, and homeostasis model of assessment (HOMA)-IR were determined. The degree of fatty liver was graded according to liver/spleen computed tomography ratio and intrahepatic vessel manifestations. Compared with the T2DM and NAFLD groups, fasting blood plasma glucose, alanine aminotransferase, gamma-glutamyl transpeptidase, TG, TNF-α, and HOMA-IR in the complicated group were significantly increased, while APN was significantly reduced. Body mass index in the complicated group was significantly higher than in the T2DM group. The complicated group was prone to severe fatty liver compared with the NAFLD group. APN was negatively correlated with body mass index, fasting blood plasma glucose, TG, TNF-α, and HOMA-IR. TNF-α was negatively correlated with APN, but positively correlated with FPG, fasting insulin, TG, and HOMA-IR. The complicated group had clear IR. A more severe degree of fatty liver was associated with higher HOMA-IR and TNF-α and lower APN. APN was an important factor for antagonizing inflammation and mitigating IR.

  3. Probiotic effect on calves infected with Salmonella Dublin: haematological parameters and serum biochemical profile.

    PubMed

    Soto, L P; Astesana, D M; Zbrun, M V; Blajman, J E; Salvetti, N R; Berisvil, A P; Rosmini, M R; Signorini, M L; Frizzo, L S

    2016-02-01

    The aim of this study was to evaluate the effect of a probiotic/lactose inoculum on haematological and immunological parameters and renal and hepatic biochemical profiles before and during a Salmonella Dublin DSPV 595T challenge in young calves. Twenty eight calves, divided into a control and probiotic group were used. The probiotic group was supplemented with 100 g lactose/calf/d and 10 10 cfu/calf/d of each strain of a probiotic inoculum composed of Lactobacillus casei DSPV318T, Lactobacillus salivarius DSPV315T and Pediococcus acidilactici DSPV006T throughout the experiment. The pathogen was administered on day 11 of the experiment, at an oral dose of 10 9 cfu/animal (LD 50 ). Aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), urea, red blood cells, haemoglobin, haematocrit, mean cell haemoglobin (MCH), mean corpuscular volume, mean corpuscular haemoglobin concentration (MCHC), white blood cells, lymphocytes, neutrophils, band neutrophils, monocytes, eosinophils, basophils and the neutrophils/lymphocytes ratio were measured on days 1, 10, 20 and 27 of the experiment. In addition, animals were necropsied to evaluate immunoglobulin A (IgA) production in the jejunal mucosa. The most significant differences caused by the administration of the inoculum/lactose were found during the acute phase of Salmonella challenge (9 days after challenge), when a difference between groups in neutrophils/lymphocytes ratio were detected. These results suggest that the probiotic/lactose inoculum administration increases the calf's ability to respond to the disease increasing the systemic immune response specific. No differences were found in haemoglobin, haematocrit, MCH, MCHC, AST, urea, GGT, band neutrophils, eosinophils, monocytes and IgA in the jejunum between the two groups of calves under the experimental conditions of this study. Further studies must be conducted to evaluate different probiotic/pathogens doses and different sampling times, to achieve a

  4. [Relationship between alcoholic liver injury and endotoxin leakage from gut and intervention effect of jianpi liqi huoxue decoction].

    PubMed

    Fang, Zhi-hong; Hu, Yi-yang; Cui, Jian-wei

    2006-09-01

    To study the effects and mechanisms of Jianpi Liqi Huoxue Decoction (JLHD) in anti-alcoholic liver injury (ALI) through the pathological relation of ALI with changes of intestinal permeability and endotoxin leakage. The liver injury model induced by Lieber-DeCarli alcoholic forage was established. Altogether 42 male SD rats were randomly divided into 4 groups, the normal group (n=6), the control group fed with non-alcohol diet (n=12), the model group fed with alcoholic diet (n=12) and the treated group fed with alcoholic diet and treated with JLHD (n=12). The medicine or distilled water was administered by gavage from the 3rd week to the end of the 6th week. Then after fasting for 5 h all the rats except those in the normal group were given lipopolysaccharide (LPS) 10 mg/kg by gavage, and the blood plasma from portal vein, serum from inferior cava vein as well as tissues of liver and intestine were prepared for detection of plasma LPS level in the portal vein to observe the change of intestinal permeability through LPS content in portal vein blood plasma, the pathological and ultrastructural changes of the small intestine by HE staining, the pathological change of liver and triglyceride (TG) content and gamma glutamyl transpeptidase (GGT) activity in liver, the changes of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, and plasma tumor necrosis factor-alpha (TNF-alpha) level. In rats after modeling, there were obvious fatty degeneration, significant increase of hepatic TG content and GGT activity, serum ALT and AST activity, as well as plasma TNF-alpha level, with high plasma LPS level indicating increased intestinal permeability, and seriously injured mucosa microvilla of small intestine. However, all the above abnormal changes were milder in the treated group than those in the model group. Meanwhile, the TNF-alpha content, endotoxin level and ALT activity were found to be positively correlated. JLHD could alleviate liver injury

  5. Blood-Based Indicators of Insulin Resistance and Metabolic Syndrome in Bottlenose Dolphins (Tursiops truncatus)

    PubMed Central

    Venn-Watson, Stephanie; Smith, Cynthia Rowe; Stevenson, Sacha; Parry, Celeste; Daniels, Risa; Jensen, Eric; Cendejas, Veronica; Balmer, Brian; Janech, Michael; Neely, Benjamin A.; Wells, Randall

    2013-01-01

    Similar to people with metabolic syndrome, bottlenose dolphins (Tursiops truncatus) can have a sustained postprandial hyperglycemia and hyperinsulinemia, dyslipidemia, and fatty liver disease. A panel of potential postprandial blood-based indicators of insulin resistance and metabolic syndrome were compared among 34 managed collection dolphins in San Diego Bay, CA, USA (Group A) and 16 wild, free-ranging dolphins in Sarasota Bay, FL, USA (Group B). Compared to Group B, Group A had higher insulin (2.1 ± 2.5 and 13 ± 13 μIU/ml), glucose (87 ± 19 and 108 ± 12 mg/dl), and triglycerides (75 ± 28 and 128 ± 45 mg/dl) as well as higher cholesterol (total, high-density lipoprotein cholesterol, and very low density lipoprotein cholesterol), iron, transferrin saturation, gamma-glutamyl transpeptidase (GGT), alanine transaminase, and uric acid. Group A had higher percent unmodified adiponectin. While Group A dolphins were older, the same blood-based differences remained when controlling for age. There were no differences in body mass index (BMI) between the groups, and comparisons between Group B and Group A dolphins have consistently demonstrated lower stress hormones levels in Group A. Group A dolphins with high insulin (greater than 14 μIU/ml) had higher glucose, iron, GGT, and BMI compared to Group A dolphins with lower insulin. These findings support that some dolphin groups may be more susceptible to insulin resistance compared to others, and primary risk factors are not likely age, BMI, or stress. Lower high-molecular weight adiponectin has been identified as an independent risk factor for type 2 diabetes in humans and may be a target for preventing insulin resistance in dolphins. Future investigations with these two dolphin populations, including dietary and feeding differences, may provide valuable insight for preventing and treating insulin resistance in humans. PMID:24130551

  6. [Results transferability on RXL, ARX, X-Pand, BN2 (Dade Behring) and modular DP (Roche Diagnostics) analysers: application to component assays of fibrotest and Actitest].

    PubMed

    Imbert-Bismut, F; Messous, D; Raoult, A; Poynard, T; Bertrand, J J; Marie, P A; Louis, V; Audy, C; Thouy, J M; Hainque, B; Piton, A

    2005-01-01

    The follow up of patients with chronic liver diseases and the data from multicentric clinical studies are affected by the variability of assay results for the same parameter between the different laboratories. Today, the main objective in clinical chemistry throughout the world is to harmonise the assay results between the laboratories after the confirmation of their traceability, in relation to defined reference systems. In this context, the purpose of our study was to verify the homogeneity of haptoglobin, apolipoprotein A1, total bilirubin, GGT activity, ALAT activity results, which are combined in Fibrotest and Actitest, between Dimension Analysers RXL, ARX and X-PAND (Dade Behring Society). Moreover, we verified the transferability of Fibrotest and Actitest results between the RXL, and either the BN2 (haptoglobin and apolipoprotein A1) or the Modular DP (total bilirubin, GGT and ALAT activity concentrations). The serum samples from 150 hospitalised patients were analysed on the different analysers. Specific protein assays were calibrated using solutions standardised against reference material on Dimension and BN2 analysers. Total bilirubin assays were performed by a diazoreaction on Dimension and Modular DP analysers. The GGT and ALAT activity measurements on the Dimension analysers were performed in accordance with the reference methods defined by the International Federation of Clinical Chemisty and Laboratory Medicine (IFCC). On the Modular, enzyme activity measurements were performed according to the Szasz method (L-gamma- glutamyl-4-nitroanilide as substrate) modified by Persijn and van der Slik (L-gamma- glutamyl-3-carboxy- 4-nitroanilide as substrat) for GGT and according to the IFCC specifications for ALAT. The methods of enzymatic activity measurement were calibrated on the Modular only. Liver fibrosis and necroinflammatory activity indices were determined using calculation algorithms, after having adjusted each component's result of Fibrotest and

  7. Military cold injury during the war in the Falkland Islands 1982: an evaluation of possible risk factors.

    PubMed

    Craig, R P

    2007-01-01

    Throughout the history of war, there have been many instances when the cold has ravaged armies more effectively than their enemies. Delineated risk factors are restricted to negro origins, previous cold injury, moderate but not heavy smoking and the possession of blood group O. No attention has been directed to the possibility that abnormal blood constituents could feasibly predispose to the development of local cold injury. This study considers this possibility and investigates the potential contribution of certain components of the circulating blood which might do so. Three groups of soldiers from two of the battalions who served during the war in the Falklands Islands in 1982 were investigated. The risk factors which were sought included the presence or absence of asymptomatic cryoglobulinaemia, abnormal total protein, albumin, individual gamma globulin or complement C3 or C4 levels, plasma hyperviscosity or evidence of chronic alcoholism manifesting as high haemoglobin, PCV, RBC, MCV or gamma glutamyl transpeptidase (GGT). No cases of cryoglobulinaemia were isolated and there was no haematological evidence to suggest that any of those men who had developed cold injury, one year before this study was performed, had abnormal circulating proteins, plasma hyperviscosity or indicators of alcohol abuse. Individual blood groups were not incriminated as a predisposing factor although the small numbers of negroes in this series fared badly. Although this investigation has excluded a range of potential risk factors which could contribute to the development of cold injury, the problem persists. Two areas of further study are needed: the first involves research into the production of better protective clothing in the form of effective cold weather boots and gloves and the second requires the delineation of those dietary and ethnic factors which allow certain communities to adapt successfully to the cold. A review of the literature in this latter area is presented.

  8. A cluster version of the GGT sum rule

    NASA Astrophysics Data System (ADS)

    Hencken, Kai; Baur, Gerhard; Trautmann, Dirk

    2004-03-01

    We discuss the derivation of a "cluster sum rule" from the Gellmann-Goldberger-Thirring (GGT) sum rule as an alternative to the Thomas-Reiche-Kuhn (TRK) sum rule, which was used as the basis up to now. We compare differences in the assumptions and approximations. Some applications of the sum rule for halo nuclei, as well as, nuclei with a pronounced cluster structure are discussed.

  9. [Reference values in the usual laboratory data for sub-Saharan immigrants. Importance in the management of infectious diseases].

    PubMed

    Sanz-Peláez, O; Angel-Moreno, A; Tapia-Martín, M; Conde-Martel, A; Carranza-Rodríguez, C; Carballo-Rastrilla, S; Soria-López, A; Pérez-Arellano, J L

    2008-09-01

    The progressive increase in the number of immigrants to Spain in recent years has made it necessary for health-care professionals to be aware about the specific characteristics of this population. An attempt is made in this study to define the normal range of common laboratory values in healthy sub-Saharan adults. Common laboratory values were studied (blood cell counts, clotting tests and blood biochemistry values) and were measured in 150 sub-Saharan immigrants previously defined as healthy according to a complete health evaluation that included a clinical history, physical examination, serologic tests and study of stool parasites. These results were compared to those from a control group consisting of 81 age-and-sex matched healthy blood donors taken from the Spanish native population. Statistically significant differences were obtained in the following values. Mean corpuscular volume (MCV), red cell distribution width (RDW), total leukocytes, and serum levels of creatinine, uric acid, total protein content, creatin-kinase (CK), aspartate aminotransferase (AST), gamma-glutamyl-transpeptidase (GGT), Immunoglobulin G (IgG) and M (IgM). If evaluated according to the normal values in native people, a considerable percentage of healthy sub-Saharan immigrants would present values (with potential clinical relevance) in the following parameters. MCV, RDW, total leukocyte counts and serum levels of CK, IgG and IgM. A proper interpretation of the common laboratory values in sub-Saharan immigrants, and probably in other foreign collectives, requires a previously-established range of normality in these parameters for those populations in order to avoid diagnostic mistakes and inadequate work-up and management.

  10. Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat.

    PubMed

    Petersen, B E; Goff, J P; Greenberger, J S; Michalopoulos, G K

    1998-02-01

    Hepatic oval cells (HOC) are a small subpopulation of cells found in the liver when hepatocyte proliferation is inhibited and followed by some type of hepatic injury. HOC can be induced to proliferate using a 2-acetylaminofluorene (2-AAF)/hepatic injury (i.e., CCl4, partial hepatectomy [PHx]) protocol. These cells are believed to be bipotential, i.e., able to differentiate into hepatocytes or bile ductular cells. In the past, isolation of highly enriched populations of these cells has been difficult. Thy-1 is a cell surface marker used in conjunction with CD34 and lineage-specific markers to identify hematopoietic stem cells. Thy-1 antigen is not normally expressed in adult liver, but is expressed in fetal liver, presumably on the hematopoietic cells. We report herein that HOC express high levels of Thy-1. Immunohistochemistry revealed that the cells expressing Thy-1 were indeed oval cells, because they also expressed alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase (GGT), cytokeratin 19 (CK-19), OC.2, and OV-6, all known markers for oval cell identification. In addition, the Thy-1+ cells were negative for desmin, a marker specific for Ito cells. Using Thy-1 antibody as a new marker for the identification of oval cells, a highly enriched population was obtained. Using flow cytometric methods, we isolated a 95% to 97% pure Thy-1+ oval cell population. Our results indicate that cell sorting using Thy-1 could be an attractive tool for future studies, which would facilitate both in vivo and in vitro studies of HOC.

  11. Coffee consumption, serum gamma-glutamyltransferase and risk of type II diabetes.

    PubMed

    Bidel, S; Silventoinen, K; Hu, G; Lee, D-H; Kaprio, J; Tuomilehto, J

    2008-02-01

    To study the joint association of coffee consumption and serum gamma-glutamyltransferase (GGT) levels on the risk of developing type II diabetes. A total of 21,826 Finnish men and women who were 35-74 years of age and without any history of diabetes at baseline (years 1982, 1987, 1992 and 1997) were included in the present analyses. They were prospectively followed up for onset of type II diabetes (n=862 cases), death or until the end of the year 2002. Coffee consumption, serum GGT and other study parameters were determined at baseline using standardized measurements. Analyses were stratified by the serum GGT level classified into two classes using the 75th sex-specific percentiles as the cut point. Coffee consumption was significantly and inversely associated with incident diabetes among both men and women. Serum GGT modified the association between coffee consumption and incident diabetes. Subjects in the high category of coffee consumption with the GGT level > or = 75th percentile showed a significant inverse association for women, and for both sexes combined. The association was not significant in subjects with the GGT level < or = 75th percentile. There was a significant interaction effect of GGT and coffee consumption on risk of type II diabetes in data of women (P=0.05) and in both sexes combined (P=0.02). Habitual coffee consumption is associated with lower incidence of type II diabetes particularly in those with higher baseline serum GGT levels.

  12. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests.

    PubMed

    Kukuk, Guido M; Schaefer, Stephanie G; Fimmers, Rolf; Hadizadeh, Dariusch R; Ezziddin, Samer; Spengler, Ulrich; Schild, Hans H; Willinek, Winfried A

    2014-10-01

    To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a

  13. Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study.

    PubMed

    Koller, Tomas; Galambosova, Martina; Filakovska, Simona; Kubincova, Michaela; Hlavaty, Tibor; Toth, Jozef; Krajcovicova, Anna; Payer, Juraj

    2017-06-14

    To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients. During a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury. Two hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes

  14. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

    PubMed Central

    2009-01-01

    Background Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. Results TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment. PMID:19943946

  15. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats.

    PubMed

    Gharib, Ola Ali

    2009-11-27

    Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  16. Hematological, biochemical effects, and self-reported symptoms in pesticide retailers.

    PubMed

    Rojas-García, Aurora Elizabeth; Medina-Díaz, Irma Martha; Robledo-Marenco, María de Lourdes; Barrón-Vivanco, Briscia Socorro; Girón-Pérez, Manuel Iván; Velázquez-Fernández, Jesús Bernardino; González-Arias, Cyndia Azucena; Albores-Medina, Arnulfo; Quintanilla-Vega, Betzabet; Ostrosky-Wegman, Patricia; Rojas-García, María Consuelo; Pérez-Herrera, Norma Elena; López-Flores, Juan Fernando

    2011-05-01

    This study evaluates the effects of exposure to pesticides on the health of pesticide retailers. The study population comprised 83-male pesticide retailers and 98 controls. Serum butyrylcholinesterase levels and complete blood analysis were performed in a certified laboratory and each subject completed a structured questionnaire. Butyrylcholinesterase activity and hematological parameters such as hemoglobin and hematocrit were significantly lower in pesticide retailers than in control subjects. In contrast, platelet count as well as hepatic parameters such as glutamic-pyruvate transaminase and gamma-glutamyl transpeptidase activities was higher in pesticide retailers. Furthermore, pesticide retailers experienced burning sensations in the skin more frequently than controls. These preliminary results suggest the importance of evaluating further toxicological biomarkers in these populations.

  17. Red-Emitting Fluorescent Probe for Detection of γ-Glutamyltranspeptidase and Its Application of Real-Time Imaging under Oxidative Stress in Cells and in Vivo.

    PubMed

    Liu, Feiyan; Wang, Zhen; Wang, Wenli; Luo, Jian-Guang; Kong, Lingyi

    2018-06-19

    γ-Glutamyltranspeptidase (GGT) plays critical roles in regulating various physiological/pathophysiological processes including the intracellular redox homeostasis. However, an effective fluorescent probe for dissecting the relationships between GGT and oxidative stress in vivo remains largely unexplored. Herein, we present a light-up fluorescent probe (DCDHF-Glu) with long wavelength emission (613 nm) for the highly sensitive and selective detection of GGT using dicyanomethylenedihydrofuran derivative as the fluorescent reporter and γ-glutamyl group as the enzyme-active trigger. DCDHF-Glu is competent to real-time image endogenous GGT in live cells and mice. In particular, DCDHF-Glu enables the direct real-time visualization of the upregulation of GGT under drug-induced oxidative stress in the HepG2 cells and the LO2 cells, as well as in vivo, vividly implying its excellent capacity in elucidation of GGT function in GGT-related biological events.

  18. Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (γ-EV) Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis.

    PubMed

    Chee, MacKenzie E; Majumder, Kaustav; Mine, Yoshinori

    2017-07-26

    Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis. The γ-EV exhibited antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine. γ-EV also reduced the phosphorylation of the signaling proteins JNK and IκBα. We concluded that γ-EV could possess an antisepsis effect against bacterial infection in intestine. This study proposes a signaling mechanism whereby the calcium-sensing receptor (CaSR) allosterically activated by γ-EV stimulates the interaction of β-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and IκBα to suppress inflammatory signaling.

  19. Structural analysis and taste evaluation of γ-glutamyl peptides comprising sulfur-containing amino acids.

    PubMed

    Amino, Yusuke; Wakabayashi, Hidehiko; Akashi, Satoko; Ishiwatari, Yutaka

    2018-03-01

    The structures, flavor-modifying effects, and CaSR activities of γ-glutamyl peptides comprising sulfur-containing amino acids were investigated. The chemical structures, including the linkage mode of the N-terminal glutamic acid, of γ-L-glutamyl-S-(2-propenyl)-L-cysteine (γ-L-glutamyl-S-allyl-L-cysteine) and its sulfoxide isolated from garlic were established by comparing their NMR spectra with those of authentic peptides prepared using chemical methods. Mass spectrometric analysis also enabled determination of the linkage modes in the glutamyl dipeptides by their characteristic fragmentation. In sensory evaluation, these peptides exhibited flavor-modifying effects (continuity) in umami solutions less pronounced but similar to that of glutathione. Furthermore, the peptides exhibited intrinsic flavor due to the sulfur-containing structure, which may be partially responsible for their flavor-modifying effects. In CaSR assays, γ-L-glutamyl-S-methyl-L-cysteinylglycine was most active, which indicates that the presence of a medium-sized aliphatic substituent at the second amino acid residue in γ-glutamyl peptides enhances CaSR activity.

  20. Arabidopsis thaliana ggt1 photorespiratory mutants maintain leaf carbon/nitrogen balance by reducing RuBisCO content and plant growth.

    PubMed

    Dellero, Younès; Lamothe-Sibold, Marlène; Jossier, Mathieu; Hodges, Michael

    2015-09-01

    Metabolic and physiological analyses of glutamate:glyoxylate aminotransferase 1 (GGT1) mutants were performed at the global leaf scale to elucidate the mechanisms involved in their photorespiratory growth phenotype. Air-grown ggt1 mutants showed retarded growth and development, that was not observed at high CO2 (3000 μL L(-1) ). When compared to wild-type (WT) plants, air-grown ggt1 plants exhibited glyoxylate accumulation, global changes in amino acid amounts including a decrease in serine content, lower organic acid levels, and modified ATP/ADP and NADP(+) /NADPH ratios. When compared to WT plants, their net CO2 assimilation rates (An ) were 50% lower and this mirrored decreases in ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) contents. High CO2 -grown ggt1 plants transferred to air revealed a rapid decrease of An and photosynthetic electron transfer rate while maintaining a high energetic state. Short-term (a night period and 4 h of light) transferred ggt1 leaves accumulated glyoxylate and exhibited low serine contents, while other amino acid levels were not modified. RuBisCO content, activity and activation state were not altered after a short-term transfer while the ATP/ADP ratio was lowered in ggt1 rosettes. However, plant growth and RuBisCO levels were both reduced in ggt1 leaves after a long-term (12 days) acclimation to air from high CO2 when compared to WT plants. The data are discussed with respect to a reduced photorespiratory carbon recycling in the mutants. It is proposed that the low An limits nitrogen-assimilation, this decreases leaf RuBisCO content until plants attain a new homeostatic state that maintains a constant C/N balance and leads to smaller, slower growing plants. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  1. Gamma-glutamyltransferase, alanine transaminase and aspartate transaminase levels and the diagnosis of gestational diabetes mellitus.

    PubMed

    Tan, Peng Chiong; Aziz, Ainul Zahaniah; Ismail, Ikram Shah; Omar, Siti Zawiah

    2012-10-01

    To evaluate gamma-glutamyltransferase (GGT), alanine transaminases (ALT) and aspartate transaminases (AST) levels and prevalent gestational diabetes mellitus (GDM). Random plasma glucose, GGT, ALT and AST and the 50-g glucose challenge test were done on antenatal women followed by diagnostic 3-point 75-g oral glucose tolerance test within two weeks. GDM was diagnosed by ADA (2011) criteria. The GDM rate was 12.2% (319/2610). Mean GGT level was higher in GDM women, 18 ± 12 vs. 16 ± 11 IU/L; P=0.03. The risk for GDM was higher for women in the highest GGT quartile band compared to the lowest: RR 1.35 95%CI 1.0-1.8; P=0.04. However, after adjustment for confounders, GGT was no longer associated with GDM. There was no correlation between ALT and AST levels and GDM. Liver transaminases do not predict GDM in contrast to type 2 diabetes. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  2. [Predictive value of liver enzymes and alcohol consumption for risk of type 2 diabetes].

    PubMed

    Ma, Xiaokun; Wang, Qingzhu; Qin, Guijun; Zhao, Yanyan; Zhang, Yinghui; Ma, Xiaojun; Li, Zhizhen; Wang, Zhimin; Ren, Gaofei; Bi, Yufang; Wang, Weiqing; Ning, Guang

    2015-01-01

    To compare the predictive value of liver enzymes and alcohol consumption for determining risk of type 2 diabetes (T2DM). A cross-sectional study was conducted in Zhengzhou with a total of 2, 693 men.Participants' height, weight, and histories of smoking and drinking were recorded. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and blood glucose, as well as related metabolic indexes were detected. Moderate daily alcohol consumption (more than 35 g ethanol/week and less than 140 g ethanol/week) decreased the risk of type 2 diabetes (OR =0.376, 95% CI:0.306 -0.463, P less than 0.05) but increased risk for higher levels of GGT and ALT (OR GGT =3.012, 95% CI:2.357-3.849, Pless than 0.01; ORALT =1.473, 95% CI:1.043-2.081, Pless than 0.05). In joint analyses of alcohol consumption and liver enzymes, the group of nondrinkers/light drinkers (less than or equal to 35 g ethanol/week) in the fourth quartile of GGT levels had the highest risk for type 2 diabetes (OR =12.219, 95% CI:6.217-24.016, P less than 0.01). The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT (nondrinkers/light drinkers in the fourth quartile of ALT levels (OR =5.357, 95% CI:3.070-9.350, P less than 0.0 1). GGT, ALT and daily alcohol consumption were independently associated with risk of type 2 diabetes. Nondrinkers/light drinkers with the highest levels ofGGT orALT were at high risk of type 2 diabetes.

  3. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis

    PubMed Central

    Abarbanel, David N.; Seki, Scott M.; Davies, Yinka; Marlen, Natalie; Benavides, Joseph A.; Cox, Kathleen; Nadeau, Kari C.; Cox, Kenneth L.

    2012-01-01

    Vancomycin has been shown to affect tumor necrosis factor-alpha (TNF-α) pathways as an immunomodulator; this is thought to be separate from its function as an antibiotic [1]. Previous studies have shown that oral vancomycin (OV) is an effective treatment for concomitant primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) in children [2, 3]. Since both diseases are associated with immune dysfunction, we hypothesized that vancomycin’s therapeutic effect in IBD and PSC occurs through immunomodulation. Therefore, we examined the in vivo immunological changes that occur during OV treatment of 14 children with PSC and IBD. Within 3 months of OV administration, peripheral gamma-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) concentrations, white blood cell (WBC) counts, and neutrophil counts normalized from elevated levels before treatment. Patients also demonstrated improved biliary imaging studies, liver biopsies and IBD symptoms and biopsies. Additionally, plasma transforming growth factor beta (TGF-β) levels were increased without concurrent shifts in Th1- or Th2-associated cytokine production. Peripheral levels of CD4+CD25hiCD127lo and CD4+FoxP3+ regulatory T (Treg) cells also increased in OV-treated PSC+IBD patients compared to pretreatment levels. A unique case study shows that the therapeutic effects of OV in the treatment of PSC+IBD do not always endure after OV discontinuation, with relapse of PSC associated with a decrease in blood Treg levels; subsequent OV retreatment was then associated with a rise in blood Treg levels and normalization of liver function tests (LFTs). Taken together, these studies support immune-related pathophysiology of PSC with IBD, which is responsive to OV. PMID:23054338

  4. Barium chloride induces redox status unbalance, upregulates cytokine genes expression and confers hepatotoxicity in rats-alleviation by pomegranate peel.

    PubMed

    Elwej, Awatef; Grojja, Yousri; Ghorbel, Imen; Boudawara, Ons; Jarraya, Raoudha; Boudawara, Tahia; Zeghal, Najiba

    2016-04-01

    The present study was performed to establish the therapeutic efficacy of pomegranate peel against barium chloride induced liver injury. Adult rats were divided into four groups of six animals each: group I, serving as controls, received distilled water; group II received by their drinking water 67 ppm of BaCl2; group III received both 67 ppm of BaCl2 by the same way than group II and 5 % of pomegranate peel (PP) via diet; group IV received 5 % of PP. Analysis by HPLC/MS of PP showed its rich composition in flavonoids such as gallic acid, castalin, hyperin, quercitrin, syringic acid, and quercetin. The protective effects of pomegranate peel against hepatotoxicity induced by barium chloride were assessed using biochemical parameters and histological studies. Exposure of rats to barium caused oxidative stress in the liver as evidenced by an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOHs), H2O2 and advanced oxidation protein product (AOPP) levels, and lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities, a decrease in catalase (CAT) and glutathione peroxidase (GPx) activities, glutathion (GSH), non-protein thiol (NPSH), vitamin C levels, and Mn-SOD gene expression. Liver total MT levels, MT-1, and MT-2 and pro-inflammatory cytokine genes expression like TNF-α, IL-1β and IL-6 were increased. Pomegranate peel, supplemented in the diet of barium-treated rats, showed an improvement of all the parameters indicated above.The present work provided ethnopharmacological relevance of pomegranate peel against the toxic effects of barium, suggesting its beneficial role as a potential antioxidant.

  5. Testicular and spermatotoxic effects of quinalphos in rats.

    PubMed

    Pant, N; Srivastava, S P

    2003-01-01

    Testicular and spermatotoxic effects were investigated in rats exposed to technical-grade quinalphos (70%) at dose levels of 0.52 mg kg(-1) (1/50th ld(50)) or 1.04 mg kg(-1) body weight (1/25th ld(50)) for 5 days a week for 60 days. The activities of marker testicular enzymes such as sorbitol dehydrogenase (SDH) and acid phosphatase were significantly decreased but those of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase were significantly increased in a dose-dependent manner. This particular pattern in the activity of testicular-cell-specific enzymes, a decrease in sperm motility and total epididymal sperm count and an increase in abnormal sperm suggest damage to germ cells and Sertoli cells. The testicular and spermatotoxic effects observed in rats may be due to the pesticide quinalphos or its metabolites. Copyright 2003 John Wiley & Sons, Ltd.

  6. Compositions of orthogonal glutamyl-tRNA and aminoacyl-tRNA synthetase pairs and uses thereof

    DOEpatents

    Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA; Santoro, Stephen [Cambridge, MA

    2009-05-05

    Compositions and methods of producing components of protein biosynthetic machinery that include glutamyl orthogonal tRNAs, glutamyl orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of glutamyl tRNAs/synthetases are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins using these orthogonal pairs.

  7. Psychiatric Comorbidity and Physical Correlates in Alcohol-dependent Patients.

    PubMed

    Gauba, Deepak; Thomas, Pramod; Balhara, Yatan P S; Deshpande, Smita N

    2016-01-01

    To examine the prevalence and pattern of comorbidity in alcohol dependence and its relationship with physical and laboratory findings. Eighty males with alcohol dependence were examined using the Hindi version of Diagnostic Interview for Genetic Studies, the International Classification of Disease-10 th Edition Personality Disorder Examination, Alcohol Use Disorder Identification Test for alcohol use, global assessment of functioning, blood sampling electrocardiogram, and ultrasonogram. Eighty-seven percent had a comorbid Axis I or an Axis II psychiatric disorder, over 78% had nicotine dependence, and 56% had comorbid Axis II disorder, antisocial personality being the most common. Gamma glutamyl transpeptidase levels were significantly associated with comorbidity. High comorbidity of Axis I psychiatric disorders was found among persons with alcohol dependence. Axis II disorders were also present.

  8. Hematologic and plasma chemistry values in captive psittacine birds.

    PubMed

    Polo, F J; Peinado, V I; Viscor, G; Palomeque, J

    1998-01-01

    Reference values for some hematologic parameters in 19 species and plasma chemical values in 11 species of Psittacine birds, including cockatoos, parrots, amazons, macaws, conures, and lories, were established for use in veterinary medicine. The following parameters were studied: hematocrit, hemoglobin concentration, erythrocyte number, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte dimensions, leukocyte number and differential leukocyte count, glucose, urea, uric acid, cholesterol, triglycerides, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine phosphokinase, lactic dehydrogenase, gamma glutamyl transpeptidase, total plasma protein, albumin, globulins, albumin-globulin ratio, sodium, potassium, calcium, magnesium, total phosphorus, chloride, and osmolality. Hematologically, the Psittacine is a very homogeneous avian group, with small differences between species. They are, however, different from other groups of birds.

  9. [Non-alcoholic fatty liver in children and adolescents with excess weight and obesity].

    PubMed

    Guijarro de Armas, M Guadalupe; Monereo Megías, Susana; Navea Aguilera, Cristina; Merino Viveros, María; Vega Piñero, M Belén

    2015-01-20

    Hepatic steatosis, also known as non-alcoholic fatty liver (NAFL), is the most frequent liver disease in obese children. Due to an increase in infantile obesity, it is experiencing a significant increment in incidence. Our objetives are: Estimate the prevalence of NAFL in children with excess weight and obesity using the glutamate pyruvate transaminase (GPT) value as a biochemical test and an abdominal ultrasound, and correlate the presence of hepatic steatosis with various anthropometric and biochemical parameters. Cross-sectional prevalence study which includes children with excess weight and obesity between the ages of 5 and 15 years, between the years 2004-2012. The independent variables included were: age, sex, weight, size, body mass index (BMI), waist circumference (WC), waist size index (WSI), insulinemia, Homeostasis model assessment-insulin resistance (HOMA-R), total cholesterol, triglycerides (TG), high density lipoproteins (HDL), low density lipoproteins (LDL), glutamic-oxaloacetic transaminase (GOT), GPT and gamma-glutamyl transpeptidase (GGT). One hundred and twenty-six patients, with an average age of 11.94 (3.12) years were recruited. A percentage of 19.66 of the patients presented elevated GPT pathology. Of the 126 abdominal ultrasounds performed, 38 patients presented hepatic steatosis (30.15%). The levels of insulinemia, HOMA-R and LDL were significantly higher in patients with altered GPT, compared to those with normal GPT values (P=.015, P=.008 and P=.002, respectively). The patients with an objective HGNA in ultrasound, also showed greater levels of insulinemia, WC, WSI, total cholesterol, TG, LDL, GLT, GPT and GGT than the patients with normal ultrasounds, thereby achieving statistical significance in insulinemia, HOMA-R, LDL and GPT values. NAFL is a relatively frequent disorder in obese children and adolescents. In our study, 2 of 10 children -using GPT- and 3 of every 10 -using abdominal ultrasound- present the same. The biochemical marker

  10. Detection of serum AFB1-lysine adduct in Malaysia and its association with liver and kidney functions.

    PubMed

    Mohd Redzwan, S; Rosita, Jamaluddin; Mohd Sokhini, A M; Nurul 'Aqilah, A R; Wang, Jia-Sheng; Kang, Min-Su; Zuraini, Ahmad

    2014-01-01

    Aflatoxin is ubiquitously found in many foodstuffs and produced by Aspergillus species of fungi. Of many aflatoxin metabolites, AFB1 is classified by the International Agency for Research on Cancer (IARC) as group one carcinogen and linked to the development of hepatocellular carcinoma (HCC). The study on molecular biomarker of aflatoxin provides a better assessment on the extent of human exposure to aflatoxin. In Malaysia, the occurrences of aflatoxin-contaminated foods have been documented, but there is a lack of data on human exposure to aflatoxin. Hence, this study investigated the occurrence of AFB1-lysine adduct in serum samples and its association with liver and kidney functions. 5ml fasting blood samples were collected from seventy-one subjects (n=71) for the measurement of AFB1-lysine adduct, albumin, total bilirubin, AST (aspartate aminotransferase), ALT (alanine transaminase), ALP (alkaline phosphatase), GGT (gamma-glutamyl transpeptidase), creatinine and BUN (blood urea nitrogen). The AFB1-lysine adduct was detected in all serum samples (100% detection rate) with a mean of 6.85±3.20pg/mg albumin (range: 1.13-18.85pg/mg albumin). Male subjects (mean: 8.03±3.41pg/mg albumin) had significantly higher adduct levels than female subjects (mean: 5.64±2.46pg/mg albumin) (p<0.01). It was noteworthy that subjects with adduct levels greater than average (>6.85pg/mg albumin) had significantly elevated level of total bilirubin (p<0.01), GGT (p<0.05) and creatinine (p<0.01). Nevertheless, only the level of total bilirubin, (r=0.347, p-value=0.003) and creatinine (r=0.318, p-value=0.007) showed significant and positive correlation with the level of AFB1-lysine adduct. This study provides a valuable insight on human exposure to aflatoxin in Malaysia. Given that aflatoxin can pose serious problem to the health, intervention strategies should be implemented to limit/reduce human exposure to aflatoxin. Besides, a study with a big sample size should be warranted in

  11. Amelioration effects against N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera.

    PubMed

    Kartik, R; Rao, Ch V; Trivedi, S P; Pushpangadan, P; Reddy, G D

    2010-12-01

    The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis. The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl(4)), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl(4), treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups. The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl(4) -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were

  12. Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

    PubMed

    Dain, Alejandro; Repossi, Gaston; Diaz-Gerevini, Gustavo T; Vanamala, Jairam; Das, Undurti N; Eynard, Aldo R

    2016-11-25

    Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory

  13. The glutathione cycle: Glutathione metabolism beyond the γ-glutamyl cycle.

    PubMed

    Bachhawat, Anand Kumar; Yadav, Shambhu

    2018-04-17

    Glutathione was discovered in 1888, over 125 years ago. Since then, our understanding of various functions and metabolism of this important molecule has grown over these years. But it is only now, in the last decade, that a somewhat complete picture of its metabolism has emerged. Glutathione metabolism has till now been largely depicted and understood by the γ-glutamyl cycle that was proposed in 1970. However, new findings and knowledge particularly on the transport and degradation of glutathione have revealed that many aspects of the γ-glutamyl cycle are incorrect. Despite this, an integrated critical analysis of the cycle has never been undertaken and this has led to the cycle and its errors perpetuating in the literature. This review takes a careful look at the γ-glutamyl cycle and its shortcomings and presents a "glutathione cycle" that captures the current understanding of glutathione metabolism. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  14. Dynamics induced by β-lactam antibiotics in the active site of Bacillus subtilis L,D-transpeptidase.

    PubMed

    Lecoq, Lauriane; Bougault, Catherine; Hugonnet, Jean-Emmanuel; Veckerlé, Carole; Pessey, Ombeline; Arthur, Michel; Simorre, Jean-Pierre

    2012-05-09

    β-lactams inhibit peptidoglycan polymerization by acting as suicide substrates of essential d,d-transpeptidases. Bypass of these enzymes by unrelated l,d-transpeptidases results in β-lactam resistance, although carbapenems remain unexpectedly active. To gain insight into carbapenem specificity of l,d-transpeptidases (Ldts), we solved the nuclear magnetic resonance (NMR) structures of apo and imipenem-acylated Bacillus subtilis Ldt and show that the cysteine nucleophile is present as a neutral imidazole-sulfhydryl pair in the substrate-free enzyme. NMR relaxation dispersion does not reveal any preexisting conformational exchange in the apoenzyme, and change in flexibility is not observed upon noncovalent binding of β-lactams (K(D) > 37.5 mM). In contrast, covalent modification of active cysteine by both carbapenems and 2-nitro-5-thiobenzoate induces backbone flexibility that does not result from disruption of the imidazole-sulfhydryl proton interaction or steric hindrance. The chemical step of the reaction determines enzyme specificity since no differences in drug affinity were observed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Gamma-Glutamyl Transpeptidase-to-Platelet Ratio Predicts Significant Liver Fibrosis of Chronic Hepatitis B Patients in China

    PubMed Central

    Ren, Tianyi; Wang, Huan; Wu, Ruihong

    2017-01-01

    Background and Aims We want to investigate whether a novel noninvasive marker is suitable for Chinese CHB patients. Methods A total of 160 treatment-naïve CHB patients who underwent liver biopsy were enrolled in our study, and we assessed the diagnostic accuracies of GPR, aspartate transaminase-to-platelet ratio index (APRI), and the fibrosis index based on 4 factors (FIB-4) in them. Results Of these 160 CHB patients, the numbers of F0, F1, F2, F3, and F4 are 34 (21.3%), 62 (38.8%), 18 (11.3%), 24 (15%), and 22 (13.8%), respectively. The area under the receiver operating characteristic curves (AUROC) of GPR for fibrosis (0.77 versus 0.70, P = 0.03), significant fibrosis (0.70 versus 0.63, P = 0.02), and extensive fibrosis (0.71 versus 0.64, P = 0.02) were significantly higher than those of APRI. The AUROCs of GPR and Fib-4 for fibrosis (0.77 versus 0.75, P = 0.14), significant fibrosis (0.70 versus 0.70, P = 0.22), extensive fibrosis (0.71 versus 0.68, P = 0.13), and cirrhosis (0.64 versus 0.67, P = 0.24) were comparable. Conclusions The GPR can be a routine laboratory marker to stage liver fibrosis in patients with CHB in China. PMID:28831282

  16. Fibrinogen storage disease in a Chinese boy with de novo fibrinogen Aguadilla mutation: Incomplete response to carbamazepine and ursodeoxycholic acid.

    PubMed

    Zhang, Mei-Hong; Knisely, A S; Wang, Neng-Li; Gong, Jing-Yu; Wang, Jian-She

    2016-08-12

    Fibrinogen storage disease (FSD) is a rare autosomal-dominant disorder caused by mutation in FGG, encoding the fibrinogen gamma chain. Here we report the first Han Chinese patient with FSD, caused by de novo fibrinogen Aguadilla mutation, and his response to pharmacologic management. Epistaxis and persistent clinical-biochemistry test-result abnormalities prompted liver biopsy in a boy, with molecular study of FGG in him and his parents. He was treated with the autophagy enhancer carbamazepine, reportedly effective in FSD, and with ursodeoxycholic acid thereafter. Inclusion bodies in hepatocellular cytoplasm stained immune-histochemically for fibrinogen. Selective analysis of FGG found the heterozygous mutation c.1201C > T (p.Arg401Trp), absent in both parents. Over more than one year's follow-up, transaminase and gamma-glutamyl transpeptidase activities have lessened but not normalized. This report expands the epidemiology of FSD and demonstrates idiosyncrasy in response to oral carbamazepine and/or ursodeoxycholic acid in FSD.

  17. Relationship between hepatic CTGF expression and routine blood tests at the time of liver transplantation for biliary atresia: hope or hype for a biomarker of hepatic fibrosis.

    PubMed

    Haafiz, Allah; Farrington, Christian; Andres, Joel; Islam, Saleem

    2011-01-01

    Progressive hepatic fibrosis (HF) is a prominent feature of biliary atresia (BA), the most common indication for liver transplantation (LT) in children. Despite its importance in BA, HF is not evaluated in routine patient care because the invasiveness of liver biopsy makes histologic monitoring of fibrosis unfeasible. Therefore, the identification of noninvasive markers to assess HF is desirable especially in children. The main goal of this pilot project was to establish an investigational framework correlating hepatic expression of fibrogenic markers with routine blood tests in BA. Using liver explants from patients with BA (n = 26), immune-expression of connective tissue growth factor (CTGF), a key fibrogenic cytokine was determined using horseradish-labeled antibodies. Expression intensities of lobular (L-CTGF) and portal (P-CTGF) CTGF were determined by using ImageJ software. These CTGF intensities were correlated with blood tests performed at the time of LT. Correlation coefficients were determined for each blood test variable versus mean L-CTGF and P-CTGF expression intensities. A P-value of less than 0.05 was considered statistically significant. All patients had end-stage liver disease and persistent cholestasis at the time of LT. Kendall tau (τ) rank correlation coefficient for L-CTGF and white blood cell (WBC) was inversed (-0.52; P ≤ 0.02). Similar but statistically nonsignificant inverse relationships were noted between L-CTGF and prothrombin time (PT) (-0.15; P ≤ 0.4), international normalized ratio (INR) (-0.14; P ≤ 0.5), and platelet count (-0.36; P ≤ 0.09). Inversed (τ) rank correlation coefficients were also evident between P-CTGF expression and gamma-glutamyl transpeptidase (GGT), PT, INR, and platelet count. Pearson correlation coefficients for combinational analysis of standardized total bilirubin (TB), alkaline phosphatase, GGT, and platelet count with L-CTGF (0.33; P = 0.3) and P-CTGF (0.06; P = 0.8), were not significant. Similar

  18. Ameliorative Effect of Camel's Milk and Nigella Sativa Oil against Thioacetamide-induced Hepatorenal Damage in Rats.

    PubMed

    Ahmad, Aftab; Al-Abbasi, Fahad A; Sadath, Saida; Ali, Soad Shaker; Abuzinadah, Mohammed F; Alhadrami, Hani A; Mohammad Alghamdi, Anwar Ali; Aseeri, Ali H; Khan, Shah Alam; Husain, Asif

    2018-01-01

    -induced hepatorenal toxicity in rats. The antihepatotxic potential of Camel's Milk (CM) and Nigella sativa oil (NSO) against thioacetamide (TAA) induced hepatorenal toxicity was evaluated in ratsThe oral administration of fresh CM (250 mL/24h/cage), NSO (2 mL/kg/day) and NSO+fresh CM and Jigreen (2 mL/kg/day) for 21 days significantly decreased the hepatorenal toxicity as evidenced from analyzed biochemical parameters in serum and histopathological studies of liver and kidney tissuesThis study demonstrated the ameliorative effects of CM and NSO against TAA induced hepatorenal toxicity. Abbreviations used: CM: Camel milk; NS: Nigella sativa ; NSO: Nigella sativa Oil; TAA: Thioacetamide; S.C.: Subcutaneous; Jig: Jigreen; b.w.: Body Weight; mL: Milli liter; mg: Milli gram; g: Gram; Kg: Kilo gram; ALT: Alanine transaminase; AST: Aspartate transaminase; GGT: Gamma-Glutamyl Transpeptidase; ALP: Alkaline Phosphatase; TC: Total Cholesterol; HDL-C: High Density Lipoprotein Cholesterol; LDL-C: Low Density Lipoprotein Cholesterol; TG: Triglyceride; TB: Total bilirubin; K + : Potassium; Na + : Sodium; CCl 4 : Carbon Tetrachloride; °C: Degree Celsius; p.o.: Per Oral; RPM: Revolutions per minute; H&E: Hematoxylin and Eosin; SEM: Standard Error of Mean; ANOVA: The one-way analysis of variance.

  19. Ameliorative Effect of Camel's Milk and Nigella Sativa Oil against Thioacetamide-induced Hepatorenal Damage in Rats

    PubMed Central

    Ahmad, Aftab; Al-Abbasi, Fahad A.; Sadath, Saida; Ali, Soad Shaker; Abuzinadah, Mohammed F.; Alhadrami, Hani A.; Mohammad Alghamdi, Anwar Ali; Aseeri, Ali H.; Khan, Shah Alam; Husain, Asif

    2018-01-01

    effects of CM, NSO, and CM plus NSO combination against TAA-induced hepatorenal toxicity in rats. SUMMARY The antihepatotxic potential of Camel's Milk (CM) and Nigella sativa oil (NSO) against thioacetamide (TAA) induced hepatorenal toxicity was evaluated in ratsThe oral administration of fresh CM (250 mL/24h/cage), NSO (2 mL/kg/day) and NSO+fresh CM and Jigreen (2 mL/kg/day) for 21 days significantly decreased the hepatorenal toxicity as evidenced from analyzed biochemical parameters in serum and histopathological studies of liver and kidney tissuesThis study demonstrated the ameliorative effects of CM and NSO against TAA induced hepatorenal toxicity. Abbreviations used: CM: Camel milk; NS: Nigella sativa; NSO: Nigella sativa Oil; TAA: Thioacetamide; S.C.: Subcutaneous; Jig: Jigreen; b.w.: Body Weight; mL: Milli liter; mg: Milli gram; g: Gram; Kg: Kilo gram; ALT: Alanine transaminase; AST: Aspartate transaminase; GGT: Gamma-Glutamyl Transpeptidase; ALP: Alkaline Phosphatase; TC: Total Cholesterol; HDL-C: High Density Lipoprotein Cholesterol; LDL-C: Low Density Lipoprotein Cholesterol; TG: Triglyceride; TB: Total bilirubin; K+: Potassium; Na+: Sodium; CCl4: Carbon Tetrachloride; °C: Degree Celsius; p.o.: Per Oral; RPM: Revolutions per minute; H&E: Hematoxylin and Eosin; SEM: Standard Error of Mean; ANOVA: The one-way analysis of variance. PMID:29576698

  20. Preparation of guinea pig macrophage for electrophoretic experiments in space

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Methods of storage and cultivation of macrophage cells in preparation for space experiments were investigated. Results show that freezing and thawing immediately after extraction did not cause any change in viability or electrophoretic mobility of the cells. A prolonged storage at -80 C did cause cell damage as indicated by a 95% reduction in variable cells. Cell damage was decreased when Glycerol or Dimethyl Sulfoxide (DMSO) was added as a cryogenic protective agent. A 100% viability was observed in cultivation experiments after two weeks due to the additional serum. Results from gamma-glutamyl transpeptidase study showed a zero activity rate. It is suggested that a flat stationary field be used for the collection and use of macrophage. It was found that a 24-hour delay in obtaining macrophage cells helps to maintain a pure culture.

  1. Establishment of the Tree Shrew as an Alcohol-Induced Fatty Liver Model for the Study of Alcoholic Liver Diseases

    PubMed Central

    Xing, Huijie; Jia, Kun; He, Jun; Shi, Changzheng; Fang, Meixia; Song, Linliang; Zhang, Pu; Zhao, Yue; Fu, Jiangnan; Li, Shoujun

    2015-01-01

    Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals’ suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs. PMID:26030870

  2. Prevalence and determinants of biochemical dysfunction of the liver in Atayal Aboriginal community of Taiwan: Is betel nut chewing a risk factor?

    PubMed Central

    Lin, Ching-Feng; Shiau, Tun-Jen; Ko, Ying-Chin; Chen, Ping-Ho; Wang, Jung-Der

    2008-01-01

    Background We address the independent and interactive roles of habitual betel quid chewing and other known risk factors for biochemical dysfunction and cirrhosis of the liver. Methods To determine the prevalence rates and risk factors associated with biochemical dysfunction of the liver, a total of 3,010 adult residents in an Atayal Aboriginal community were invited to participate in the study. Abdominal ultrasonography was used to diagnose liver cirrhosis. Results There were 2,063 Atayal Aboriginal and 947 non-Aboriginal in this study. The result showed overall prevalence rates for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) were 21.2 % and 2.9 %, respectively. There were 16.5 %, 15.1 % and 22.4 % subjects with abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transpeptidase (GGT), accordingly. Multiple logistic regression analysis showed that combined infections with HBV and HCV presented with the highest risks with OR (odds ratio) and 95% CI (confidence interval) of 4.2 (1.2–17.4) and 3.8 (1.0–14.1), respectively for elevation of ALT and AST; followed by alcohol (1.7 and 3.1), male gender (1.7 and 1.6), betel quid (1.5 and 1.3), smoking (1.4 and 1.8), and aboriginal (1.4 and 1.3). There is effect-measure modification between viral infection and betel quid chewing for increased severity of abnormal ALT elevation. Among 1,382 subjects consenting to abdominal ultrasonography, 41(3.0%) were found to have liver cirrhosis with the same factors associated with higher risks. Conclusion In addition to infections with viral hepatitis B and/or C, we found Atayal Aboriginal, males, current smokers, drinkers and betel quid chewers were independently associated with biochemical dysfunction and probably cirrhosis of the liver. Further study is needed to corroborate the above hypothesis. PMID:18439308

  3. Blood plasma chemistries from wild mourning doves held in captivity.

    PubMed

    Schulz, J H; Bermudez, A J; Tomlinson, J L; Firman, J D; He, Z

    2000-07-01

    Despite the extensive amount of research conducted on mourning doves (Zenaida macroura), no biochemical reference values exist for this species. Our objective, therefore, was to establish base line clinical chemistry reference values for mourning doves to assist with establishing clinical diagnoses. Wild mourning doves were captured 19 March 1996 to 8 August 1996, and 6 February 1998 to 12 May 1998; blood samples were collected from 382 mourning doves. Plasma biochemical values were established for glucose, sodium, potassium, chloride, enzymatic CO2, albumin, total protein, globulin, calcium, phosphorus, cholesterol, magnesium, aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), and uric acid. These reference values are invaluable for determining diagnosis of diseases of the gastrointestinal, hepatic, renal, cardiovascular, musculoskeletal, and endocrine systems.

  4. Inverse associations of total and decaffeinated coffee with liver enzyme levels in NHANES 1999–2010

    PubMed Central

    Xiao, Qian; Sinha, Rashmi; Graubard, Barry I.; Freedman, Neal D.

    2014-01-01

    Background Coffee may have hepatoprotective effects and higher coffee consumption has been associated inversely with levels of liver enzymatic markers. However, it is unclear whether decaffeinated coffee is also associated with liver enzymes. Methods The study population included 27,793 participants, age 20 or older, in the US National Health and Nutrition Examination Survey (1999–2010). Coffee intake was evaluated by 24-hour dietary recall. Serum levels of aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transaminase (GGT) were measured. We examined the relationship between coffee intake and enzymatic levels using weighted multiple variable logistic (abnormally elevated levels of enzymes) and linear regression (continuous enzymatic levels). Results Total coffee consumption was inversely associated with abnormal levels of all four liver enzymes and continuous levels of AST, ALP and GGT. Compared to those reporting no coffee consumption, participants reporting ≥3 cups per day had an odds ratio (OR) (95% confidence interval (CI)) of 0.75 (0.63, 0.89)), 0.82 (0.68, 0.98), 0.73 (0.55, 0.95) and 0.69 (0.57, 0.83) for abnormal levels of ALT, AST, ALP and GGT, respectively. Similar inverse associations were found with decaffeinated coffee intake and abnormal levels of ALT (OR≥2 vs 0 cup/d: 0.62 (0.41, 0.94)), AST (0.74 (0.49, 1.11)), and GGT (0.70, 0.49–1.00). Conclusion Higher intakes of coffee, regardless of its caffeine content, were associated with lower levels of liver enzymes. PMID:25124935

  5. Serum gamma-glutamyltransferase activity is increased in patients with calcific aortic valve stenosis.

    PubMed

    Bozbas, Huseyin; Yildirir, Aylin; Demir, Ozlem; Cakmak, Abdulkadir; Karacaglar, Emir; Yilmaz, Mustafa; Eroglu, Serpil; Pirat, Bahar; Ozin, Bulent; Muderrisoglu, Haldun

    2008-07-01

    A growing body of data indicates an independent association between serum gamma-glutamyltransferase (GGT) activity, a marker of increased oxidative stress, and cardiovascular diseases. The process of calcific aortic valve disease has been shown to present characteristics of atherosclerosis. The study aim was to evaluate the possible role of serum GGT in patients with calcific aortic valve disease. The results of patients' echocardiography studies from 2005 for the presence of calcific aortic valve disease in the forms of aortic stenosis (AS) and aortic valve calcification (AVC) without significant valve stenosis, were retrospectively evaluated. Age-and gender-matched patients with normal aortic valve morphology were selected at random as a control group. A total of 383 patients was enrolled into the study (126 with AS, 133 with AVC, 124 controls). Serum GGT activity, along with other liver enzyme analyses and laboratory results, were determined and compared among the groups. Age, gender and clinical and laboratory results were similar among the three groups. Median serum GGT levels in the AS, AVC and control groups were 23.0 U/1 (mean 31.5 +/- 24.9 U/1), 22.0 U/1 (mean 27.6 +/- 18.6 U/) and 18.0 U/l (mean 22.4 +/- 16.4 U/l), respectively. Compared to controls, AS patients had significantly higher serum GGT and C-reactive protein levels, while the differences between AVC patients and controls for these parameters were not significant. The study results suggest that serum GGT activity is increased in patients with calcific AS. These increases seem to occur in advanced rather than milder forms of calcific aortic valve disease.

  6. Associated liver enzymes with hyperlipidemic profile in type 2 diabetes patients.

    PubMed

    Al-Jameil, Noura; Khan, Farah A; Arjumand, Sadia; Khan, Mohammad F; Tabassum, Hajera

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and is associated with dyslipidemia and disturbed liver function. Aim of the present work is to assess the liver enzymes and to find its association with hyperlipidemic profile in T2DM. Total of 157 subjects were studied and divided into two groups; diabetes (n=81) and non-diabetes (n=76). Various biochemical parameters like fasting glucose, post prandial glucose, HbA1c, total cholesterol (TC), triglycerides (Tg), high density lipoprotein cholesterol (HDL-C), alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl transferase (GGT) were analyzed by ROCHE module Cobas 6000 (C501 & C601) analyzer, kits were procured by ROCHE diagnostics. Low density lipoprotein cholesterol (LDL-C) was estimated by Freidwald's formula. Statistical analysis was performed by applying student t test and Pearson's correlation coefficient, at 0.0001 and 0.05 level of significance, respectively. All the glycemic control parameters, lipid profile parameters except HDL-C and liver enzymes were found increased in diabetes group and significantly differ from non-diabetes group (p>0.0001). ALT showed significant positive correlation with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and GGT at p>0.05. AST showed very weak relation with all parameters while GGT was positively associated with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and ALT at p>0.05. In conclusion, T2DM incline to elevate liver enzymes, especially ALT and GGT were of significance. Routine screening of ALT and GGT in T2DM patients may assists early detection of liver abnormalities and to arrest the progress of disease.

  7. Bioaccumulation of methyl parathion and its toxicology in several species of the freshwater community in Ignacio Ramirez dam in Mexico.

    PubMed

    De La Vega Salazar, M Y; Tabche, L M; García, C M

    1997-10-01

    Environmental contamination by pesticides, including the presence of chemical residues in aquatic wildlife, is a widespread ecological problem. Methyl parathion (MP), a widely used organophosphorate insecticide, is a potent neurotoxic in both vertebrates and invertebrates. The effect of a subchronic exposure to MP in aquatic organisms was evaluated in a natural ecosystem measuring acetyl cholinesterase (AChE) and gamma glutamil transpeptidase (GGT) activity. Two samples were conducted. Physicochemical characterization was done at each sampling time and organisms were collected. MP and metabolite 4-nitrophenol (4-NP) concentrations were measured in water sediment and organisms. The major differences in physical features between season were an increase of turbidity and salinity and depletion of dissolved oxygen in the rainy season. MP and 4-NP are bioconcentrated in organisms in response to environmental stress. MP concentration was measured in different size/age and reproductive stages separately. A significant concentration in reproductive tissues (plants)/unborn progeny (animals) was always found, and this can affect egg viability. The metabolite 4-NP is bioaccumulated and is toxic because it causes an increase of AChE activity. GGT activity was higher than that in controls. The increase in enzymatic activity provides a detoxification mechanism from chronic sublethal exposure, when hepatic glutation depletion occurs, and may be an indicator of liver damage.

  8. A Reaction Path Study of the Catalysis and Inhibition of the Bacillus anthracis CapD gamma-Glutamyl Transpeptidase

    DTIC Science & Technology

    2014-10-21

    lases.11,30,31 The first bound structure of CapD [Protein Data Bank ( PDB ) entry 3G9K] was determined with a di-α-L-Glu ligand.29 The di-α-L-Glu ligand...Article dx.doi.org/10.1021/bi500623c | Biochemistry 2014, 53, 6954−69676956 into the CapD structure ( PDB entry 3G9K29) identified two principal...in capsule anchoring and remodeling makes the enzyme a promising target for anthrax medical countermeasures. Although the structure of CapD is known

  9. Post-translational glutamylation and tyrosination in tubulin of tritrichomonads and the diplomonad Giardia intestinalis.

    PubMed

    Boggild, A K; Sundermann, C A; Estridge, B H

    2002-01-01

    Glutamylated and tyrosinated tubulin were localized in Giardia intestinalis and selected trichomonads of the Tritrichomonadinae subfamily, using specific monoclonal antibodies directed at each of the post-translational modifications. Analysis was carried out using indirect immunofluorescence microscopy. Although trichomonad tubulins remained unlabeled by anti-tyrosine tubulin (TUB-1A2), the presence of the glutamylation motif (GT 335) was confirmed and found to differ in distribution among tritrichomonads. Tritrichomonas muris was most heavily labeled with GT 335, while T. foetus was the least so. Like trichomonads, Giardia was unreactive to anti-tyrosine tubulin; however, the GT 335 antibody produced marked fluorescence in Giardia trophozoites. This study is the first to report immunofluorescent localization of tubulin glutamylation in Giardia and confirms previously reported mass spectrometry data.

  10. Dose-effect relation between daily ethanol intake in the range 0-70 grams and %CDT value: validation of a cut-off value.

    PubMed

    Schellenberg, François; Schwan, Raymund; Mennetrey, Louise; Loiseaux, Marie-Nadia; Pagès, Jean Christophe; Reynaud, Michel

    2005-01-01

    To evaluate the ability to infer alcohol consumption using the %CDT (carbohydrate deficient transferrin) immunoassay (Axis Shield). One hundred and eighty-three healthy subjects (143 men, 40 women) undergoing a routine medical check-up at their workplace declared frequency and quantity of alcohol consumption covering the last 4 weeks. Seven sub-groups were made up from this population, according to daily ethanol intake and by increments of 10 g from 0 to 70 g/day. A reference group that consisted of 133 healthy teetotallers (74 men, 59 women) was recruited by occupational medicine in the same conditions as the 183 subjects of the study. Percentage CDT and gamma glutamyl transferase (GGT) were assayed on a fasting blood sample. There was a proportional dose-response effect of daily ethanol intake on %CDT values in the range of 0-70 g per day. A threshold effect on %CDT values for patients having an alcohol intake of over 40 g per day was found, an effect which was not observed for GGT activity. The kit has clinical usefulness, and the value of 2.6% proposed by the manufacturer for the cut-off for hazardous drinking in both sexes has been validated.

  11. Zingiber officinale acts as a nutraceutical agent against liver fibrosis

    PubMed Central

    2011-01-01

    Background/objective Zingiber officinale Roscoe (ginger) (Zingiberaceae) has been cultivated for thousands of years both as a spice and for medicinal purposes. Ginger rhizomes successive extracts (petroleum ether, chloroform and ethanol) were examined against liver fibrosis induced by carbon tetrachloride in rats. Results The evaluation was done through measuring antioxidant parameters; glutathione (GSH), total superoxide dismutase (SOD) and malondialdehyde (MDA). Liver marker enzymes; succinate and lactate dehydrogenases (SDH and LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP), 5'- nucleotidase (5'NT) and liver function enzymes; aspartate and alanine aminotransferases (AST and ALT) as well as cholestatic markers; alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin were estimated. Liver histopathological analysis and collagen content were also evaluated. Treatments with the selected extracts significantly increased GSH, SOD, SDH, LDH, G-6-Pase, AP and 5'NT. However, MDA, AST, ALT ALP, GGT and total bilirubin were significantly decreased. Conclusions Extracts of ginger, particularly the ethanol one resulted in an attractive candidate for the treatment of liver fibrosis induced by CCl4. Further studies are required in order to identify the molecules responsible of the pharmacological activity. PMID:21689445

  12. Usefulness of admission gamma-glutamyltransferase level for predicting new-onset heart failure in patients with acute coronary syndrome with left ventricular systolic dysfunction.

    PubMed

    Sarıkaya, Savaş; Aydın, Gülay; Yücel, Hasan; Kaya, Hakkı; Yıldırımlı, Kutay; Başaran, Ahmet; Zorlu, Ali; Sahin, Safak; Akyol, Lütfü; Bulut, Musa

    2014-04-01

    Our aim was to determine whether there is a relationship between admission gamma-glutamyltransferase (GGT) and subsequent heart failure hospitalizations in patients with acute coronary syndrome. We selected 123 patients with newly diagnosed acute coronary syndrome of ejection fraction (EF) <45%. Patients were followed 15±10 months, and the relationship between admission GGT level and hospitalization because of heart failure during the follow-up was examined. Twenty-three (18.7%) patients were hospitalized during the follow-up of 15±10 months. Receiver operating characteristic (ROC) curve analysis showed that the cut-off point of admission GGT related to predict hospitalization was 49 IU/L, with a sensitivity of 81.7% and specificity of 65.2%. Increased GGT >49 IU/L on admission, presence of hypertension and hyperlipidemia, left ventricular ejection fraction (LVEF), right ventricular dysfunction, moderate-to-severe mitral regurgitation, alanine aminotransferase level, and antiplatelet agent usage were found to have prognostic significance in univariate Cox proportional hazards analysis. In multivariate Cox proportional-hazards model, increased GGT >49 IU/L on admission (hazard ratio [HR] 2.663, p=0.047), presence of hypertension (HR 4.107, p=0.007), and LVEF (HR 0.911, p=0.002) were found to be independent factors to predict new-onset heart failure requiring hospitalization. Hospitalization in heart failure was associated with increased admission GGT levels. Increased admission GGT level in acute coronary syndrome with heart failure should be monitored closely and treated aggressively.

  13. [Protective effect of emodin pretreatment in young rats with intrahepatic cholestasis].

    PubMed

    Xiong, Xiao-Li; Yan, Su-Qi; Qin, Huan; Zhou, Li-Shan; Zhang, Ling-Ling; Jiang, Zhi-Xia; Ding, Yan

    2016-02-01

    To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain

  14. Amelioration effects against N-nitrosodiethylamine and CCl4-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera

    PubMed Central

    Kartik, R.; Rao, Ch. V.; Trivedi, S.P.; Pushpangadan, P.; Reddy, G.D.

    2010-01-01

    Objective: The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis. Materials and Methods: The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl4), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl4, treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups. Results: The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl4 -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The

  15. Tubulin Glutamylation Regulates Ciliary Motility by Altering Inner Dynein Arm Activity

    PubMed Central

    Suryavanshi, Swati; Eddé, Bernard; Fox, Laura A.; Guerrero, Stella; Hard, Robert; Hennessey, Todd; Kabi, Amrita; Malison, David; Pennock, David; Sale, Winfield S.; Wloga, Dorota; Gaertig, Jacek

    2010-01-01

    SUMMMARY How microtubule-associated motor proteins are regulated is not well understood. A potential mechanism for spatial regulation of motor proteins is provided by post-translational modifications of tubulin subunits that form patterns on microtubules. Glutamylation is a conserved tubulin modification [1] that is enriched in axonemes. The enzymes responsible for this PTM, glutamic acid ligases (E-ligases), belong to a family of proteins with a tubulin tyrosine ligase (TTL) homology domain (TTL-like or TTLL proteins) [2]. We show that in cilia of Tetrahymena, TTLL6 E-ligases generate glutamylation mainly on the B-tubule of outer doublet microtubules, the site of force production by ciliary dynein. Deletion of two TTLL6 paralogs caused severe deficiency in ciliary motility associated with abnormal waveform and reduced beat frequency. In isolated axonemes with a normal dynein arm composition, TTLL6 deficiency did not affect the rate of ATP-induced doublet microtubule sliding. Unexpectedly, the same TTLL6 deficiency increased the velocity of microtubule sliding in axonemes that also lack outer dynein arms, in which forces are generated by inner dynein arms. We conclude that tubulin glutamylation on the B-tubule inhibits the net force imposed on sliding doublet microtubules by inner dynein arms. PMID:20189389

  16. Association of serum gamma-glutamyltransferase and alanine aminotransferase activities with risk of type 2 diabetes mellitus independent of fatty liver.

    PubMed

    Kim, Chul-Hee; Park, Joong-Yeol; Lee, Ki-Up; Kim, Jin-Ho; Kim, Hong-Kyu

    2009-01-01

    Although elevated serum concentrations of gamma-glutamyltrans- ferase (GGT) or alanine aminotransferase (ALT) have been associated with type 2 diabetes mellitus, it is unclear whether each is an independent predictor of type 2 diabetes or merely a surrogate marker for fatty liver or hepatic injury. We assessed clinical and laboratory findings in 3556 non-diabetic subjects (2217 men, 1339 women; age, 45.7 +/- 8.1 (range 20-79) years) without fatty liver or clinically significant hepatic dysfunction who underwent voluntary medical check-ups at a 5-year interval. The odds ratio of developing type 2 diabetes increased significantly with increasing GGT and ALT levels at baseline. In multiple logistic regression models adjusted for age, sex, alcohol consumption, smoking, body mass index (BMI), triglycerides, high-density lipoprotein (HDL)-cholesterol, fasting glucose, and ALT, the highest quartile of GGT remained significantly associated with type 2 diabetes. Compared with the first GGT quartile, the odds ratios of the second, third, and fourth GGT quartiles were 0.64 (95% CI, 0.25-1.65), 1.12 (0.45-2.78), and 3.07 (1.21-7.76), respectively. The adjusted odds ratios for the second, third, and fourth ALT quartiles in the same logistic regression model were 2.40 (0.83-6.94), 2.85 (1.03-7.90), and 4.31 (1.56-11.88), respectively. The risk of type 2 diabetes was additive with respect to GGT and ALT quartiles. Increased serum GGT and ALT levels are independent, additive risk factors for the development of type 2 diabetes mellitus in subjects without fatty liver or hepatic dysfunction. Copyright 2009 John Wiley & Sons, Ltd.

  17. Enzymatic and histopathologic biomarkers as indicators of contaminant exposure and effect in Asian clam (Potamocorbula amurensis)

    USGS Publications Warehouse

    Teh, S.J.; Clark, S.L.; Brown, C.L.; Luoma, S.N.; Hinton, D.E.

    1999-01-01

    Enzymatic and histopathologic alterations of the digestive gland, gill, gonad, and kidney were studied in Asian clam (Potamocorbula amurensis) in April, 1997 from each of four United States Geological Survey (USGS) stations in the San Francisco Estuary. Stations were selected based on differing body burdens of metallic contaminants in clams (Stn 4.1>6.1>8.1>12.5) observed over 7 years. Because no pristine sites are known within the estuary and because no laboratory-reared stocks of P. amurensis were available, clams from station 12.5 served as reference animals. Histopathologic analysis revealed no lesions in clams collected from station 12.5. Mild digestive gland atrophy and moderate distal kidney tubular vacuolation were seen in clams collected from station 8.1. Mild digestive gland atrophy, moderate kidney tubular atrophy, and moderate gill inflammation were seen in clams collected from station 6.1. Lesions found only in clams from station 4.1 were: (1) severe inflammation and moderate atrophy of primary ducts and diverticula, and decreased numbers of heterophagosomes and heterolysosomes in diverticula of the digestive gland; (2) severe gill inflammation; (3) severe kidney tubular atrophy; (4) severe ovarian and testicular inflammation and necrosis (5) decreased numbers of mature ova; and (6) decreased number of glycogen storage cells in the ovary and testis. Localization of specific enzymes including adenosine triphosphatase (ATP), acid phosphatase (ACP), alkaline phosphatase (ALKP), gamma-glutamyl transpeptidase (GGT), and glucose-6-phosphate dehydrogenase (G6PDH) was performed and correlated, in serial sections with glycogen (PAS) and haematoxylin and eosin stains. Enzymatic analysis revealed: (1) increased digestive diverticula ATP in stations 6.1 and 4.1; (2) decreased digestive diverticula ACP in stations 6.1 and 4.1 and proximal kidney tubular ACP deficiency in station 4.1; (3) no ALKP differences among stations; (4) increased distal kidney tubular GGT at

  18. Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity

    PubMed Central

    2013-01-01

    Background Having considered how bioavailable aluminium (Al) may affect ecological systems and animals living there, especially cattle, and in search for a preventive dietary treatment against Al toxicity, we aimed to test the protective role of fenugreek seeds against chronic liver injury induced by aluminum chloride (AlCl3) in Wistar rats. Results Five months of AlCl3 oral exposure (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) caused liver atrophy, an inhibition of aspartate transaminase (AST), alanine transaminase (ALT) and glutamyl transpeptidase (GGT), an enhancement of both lipid peroxidation and lactate dehydrogenase (LDH) activity and an increase of total protein level in liver. Moreover, histopathological and histochemical examinations revealed moderate alterations in the hepatic parenchyma in addition to a disrupted iron metabolism. Co-administration of fenugreek seed powder (FSP) at 5% in pellet diet during two months succeeded to antagonize the harmful effects of AlCl3 by restoring all tested parameters. Conclusion This study highlighted the hepatotoxicity of AlCl3 through biochemical and histological parameters in one hand and the hepatoprotective role of fenugreek seeds on the other hand. Thus this work could be a pilot study which will encourage farmers to use fenugreek seeds as a detoxifying diet supplement for domestic animals. PMID:23363543

  19. [Value of non-invasive models of liver fibrosis in judgment of treatment timing in chronic hepatitis B patients with ALT < 2×upper limit of normal].

    PubMed

    Zhou, Q Q; Hu, Y B; Zhou, K; Zhang, W W; Li, M H; Dong, P; Di, J G; Hong, L; Du, Q W; Xie, Y; Sun, Q F

    2016-09-20

    Objective: To investigate the value of non-invasive liver fibrosis models, FIB-4, S index, aspartate aminotransferase to platelet ratio index(APRI), globulin-platelet(GP)model, aspartate aminotransferase/platelet/gamma-glutamyl transpeptidase/alpha-fetoprotein(APGA), and platelet/age/phosphatase/alpha-fetoprotein/aspartate aminotransferase(PAPAS), in the diagnosis of marked liver fibrosis in chronic hepatitis B(CHB)patients with ALT < 2×upper limit of normal(ULN), as well as treatment timing for this population. Methods: A total of 389 CHB patients with ALT < 2×ULN who were admitted to Beijing Ditan Hospital and whose treatment timing was difficult to judge were enrolled. Transdermal liver biopsy was performed to obtain pathological results, and routine serological tests were performed, including routine blood test, serum biochemical parameters, hepatitis B virus(HBV)markers, and HBV DNA. According to liver pathology, the patients were divided into non-marked liver fibrosis group(S < 2)with 324 patients and marked liver fibrosis group(S≥2)with 65 patients. The non-invasive models for predicting liver fibrosis was established with reference to original articles. SPSS 19.0 software was used for statistical analysis, and the receiver operating characteristic(ROC)curve was used to compare the value of different non-invasive models in predicting marked liver fibrosis in this population. Results: All the non-invasive models had a certain diagnostic value for liver fibrosis degree in these patients, and the areas under the ROC curve for APRI, FIB-4, APGA, S index, PAPAS, and GP model were 0.718, 0.691, 0.758, 0.729, 0.673, and 0.691, respectively. APGA had the largest area under the ROC curve(0.758, 95% CI 0.673-0.844), and gamma-glutamyl transpeptidase was significantly positively correlated with liver fibrosis degree. Conclusion: The non-invasive models of liver fibrosis can identify marked liver fibrosis in CHB patients with ALT < 2×ULN in whom it is difficult to

  20. [Effects of moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) on liver function in rats with precancerous lesion of hepatic cellular cancer].

    PubMed

    Liu, Yang; Hou, Zhongwei; Lu, Jun; Dong, Feng; Wang, Pei; Jia, Wenrui; Wang, Chaoyang

    2015-07-01

    To explore the effects of moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) on liver furiction and morphology in rat with precancerous lesion of hepatic cellular cancer MCC). A total of 60 male Wistar rats were randomly divided into a normal group (10 rats), a model group (20 rats), a 20-day treatment group (15 rats) and a 40-day treatment group (15 rats). HCC model was established by intraperitoneal injection of diethylnitrosamine (DEN). Rats in the normal group received no treatment. Rats in the model group were treated with fixation. Rats in the 20-day treatment group and 40-day treatment group were treated by moxibustion with seed-sized moxa cone at "Ganshu" (BL 18), once every other day, for 20 days and 40 days, respectively. Blood sample in each group was collected 1 d before model establishment, 20 d, 40 d and 84 d after model establishment. Chemical method was applied to test the activity of ALT (alamine aminotransferase), AST (aspartate transaminase) and GGT (glutamyl transpeptidase); at the end of model establishment, all the rats were sacrificed to observe the liver morphology changes. After the first therapeutic course, the. content of ALT and AST in the 20-day treatment group was significantly lower than that in the model group (all P<0. 05); after the second therapeutic course, the content of ALT, AST and GGT in the 40-day treatment group was insignificantly lower than that in the model group (all P>0. 05). Under light microscope, the slice of liver tissue indicated that primary tumor was induced in the model group, and the tumor cells were stained and irregular; the cytoplasm in the 20-day treatment group was even, and the tumor cells were few with several nodules alone. In the 40-day treatment group the liver morphology was normal and the staining was even; the tumor cells were few without nodules or a few. Conclusion Moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) could reduce the serum content of ALT, AST and GGT in rats with HCC

  1. Comparative assessment of a DNA and protein Leishmania donovani gamma glutamyl cysteine synthetase vaccine to cross-protect against murine cutaneous leishmaniasis caused by L. major or L. mexicana infection.

    PubMed

    Campbell, S A; Alawa, J; Doro, B; Henriquez, F L; Roberts, C W; Nok, A; Alawa, C B I; Alsaadi, M; Mullen, A B; Carter, K C

    2012-02-08

    Leishmaniasis is a major health problem and it is estimated that 12 million people are currently infected. A vaccine which could cross-protect people against different Leishmania spp. would facilitate control of this disease as more than one species of Leishmania may be present. In this study the ability of a DNA vaccine, using the full gene sequence for L. donovani gamma glutamyl cysteine synthetase (γGCS) incorporated in the pVAX vector (pVAXγGCS), and a protein vaccine, using the corresponding recombinant L. donovani γGCS protein (LdγGCS), to protect against L. major or L. mexicana infection was evaluated. DNA vaccination gave transient protection against L. major and no protection against L. mexicana despite significantly enhancing specific antibody titres in vaccinated infected mice compared to infected controls. Vaccination with the LdγGCS protected against both species but only if the protein was incorporated into non-ionic surfactant vesicles for L. mexicana. The results of this study indicate that a L. donovani γGCS vaccine could be used to vaccinate against more than one Leishmania species but only if the recombinant protein is used. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Oral cancer.

    PubMed

    Gerson, S J

    1990-01-01

    In the U.S. oral cancer accounts for 2.1% of all cancers and 1% of cancer deaths. Two to three times as many males as females are affected. Blacks have more intra-oral cancer than whites, and their incidence and mortality rates have increased in recent years. The etiologic process very likely involves several factors. The major etiologic agents are tobacco (all types) and alcoholic beverages. Herpes simplex virus, human papilloma virus, and Candida have been implicated. Host factors include poor state of dentition, nutritional aberrations, cirrhosis of liver, lichen planus, and immunologic impairmant. Cellular changes include amplification of some oncogenes, alterations in antigen expression, production of gamma-glutamyl transpeptidase, and disturbance of keratin and involucrin production. Experimentally, cancer is readily produced on the hamster cheek pouch and rat oral mucosa. Unlike oral cancer in humans, most experimental lesions are exophytic, and they rarely metastasize.

  3. Characterization of brush borders purified in iso-osmotic medium and microvillar membranes subfractionated from mouse small intestine.

    PubMed Central

    Fujita, M; Ohta, H; Uezato, T

    1981-01-01

    Brush borders free of nuclei were isolated by repeated homogenization and centrifugation in iso-osmotic medium. They showed typical morphology under electron microscopy. The mean recovery and enrichment of alkaline phosphatase activity in the brush-border fraction were 50% and 17.5-fold respectively. gamma-Glutamyl transpeptidase showed a close parallelism with alkaline phosphatase and sucrase in subcellular distribution. Microvillar membranes were purified from isolated brush borders; they showed a further enrichment for alkaline phosphatase and were composed of homogeneous vesicles. Both brush-border and microvillar-membrane preparations were analysed for contamination by basolateral and endoplasmic-reticular membranes. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the microvillar-membrane preparation in six different systems revealed approx. 40 components in the mol.wt. range 15 000-232 000. They were grouped into seven major classes on the basis of molecular weight and electrophoretic patterns. Images PLATE 1 PLATE 2 PMID:7317008

  4. Gamma-glutamyltransferase, fatty liver index and hepatic insulin resistance are associated with incident hypertension in two longitudinal studies.

    PubMed

    Bonnet, Fabrice; Gastaldelli, Amalia; Pihan-Le Bars, Florence; Natali, Andrea; Roussel, Ronan; Petrie, John; Tichet, Jean; Marre, Michel; Fromenty, Bernard; Balkau, Beverley

    2017-03-01

    We hypothesized that liver markers and the fatty liver index (FLI) are predictive of incident hypertension and that hepatic insulin resistance plays a role. The association between liver markers and incident hypertension was analysed in two longitudinal studies of normotensive individuals, 2565 from the 9-year data from an epidemiological study on the insulin resistance cohort and the 321 from the 3-year 'Relationship between Insulin Sensitivity and Cardiovascular disease' cohort who had a measure of endogenous glucose production. The FLI is calculated from BMI, waist circumference, triglycerides and gamma-glutamyltransferase (GGT) and the hepatic insulin resistance index from endogenous glucose production and fasting insulin. The incidence of hypertension increased across the quartiles groups of both baseline GGT and alanine aminotransferase. After adjustment for sex, age, waist circumference, fasting glucose, smoking and alcohol intake, only GGT was significantly related with incident hypertension [standardized odds ratio: 1.21; 95% confidence interval (1.10-1.34); P = 0.0001]. The change in GGT levels over the follow-up was also related with an increased risk of hypertension, independently of changes in body weight. FLI analysed as a continuous value, or FLI at least 60 at baseline were predictive of incident hypertension in the multivariable model. In the RISC cohort, the hepatic insulin resistance index was positively related with the risk of 3-year incident hypertension [standardized odds ratio: 1.54 (1.07-2.22); P = 0.02]. Baseline GGT and FLI, as well as an increase in GGT over time, were associated with the risk of incident hypertension. Enhanced hepatic insulin resistance predicted the onset of hypertension and may be a link between liver markers and hypertension.

  5. Association between long working hours and serum gamma-glutamyltransferase levels in female workers: data from the fifth Korean National Health and Nutrition Examination Survey (2010-2011).

    PubMed

    Park, Seung-Gwon; Lee, Yong-Jin; Ham, Jung-Oh; Jang, Eun-Chul; Kim, Seong-Woo; Park, Hyun

    2014-01-01

    The present study investigated the association between long working hours and serum gamma-glutamyltransferase (GGT) levels, a factor influencing the incidence of cardiovascular disease. Data from the fifth Korean National Health and Nutrition Examination Survey (2010-2011) were used to analyze 1,809 women. Subjects were divided into three groups based on the number of weekly working hours: ≤29, 30-51, and ≥52 hours per week. Complex samples logistic regression was performed after adjusting for general and occupational factors to determine the association between long working hours and high serum GGT levels. The prevalence of high serum GGT levels in groups with ≤29, 30-51, and ≥52 working hours per week was 22.0%, 16.9%, and 26.6%, respectively. Even after adjusting for general and occupational factors, those working 30-51 hours per week had the lowest prevalence of high serum GGT levels. Compared to those working 30-51 hours per week, the odds ratios (OR) of having high serum GGT levels in the groups with ≥52 and ≤29 working hours per week were 1.56 (95% confidence interval [CI], 1.10-2.23) and 1.53 (95% CI, 1.05-2.24), respectively. Long working hours were significantly associated with high serum GGT levels in Korean women.

  6. Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

    PubMed Central

    Lim, Tong-Hye; Nor-Amdan, Nur-Asyura

    2017-01-01

    Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver. PMID:28280515

  7. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress.

    PubMed

    Colacino, Justin A; Arthur, Anna E; Ferguson, Kelly K; Rozek, Laura S

    2014-05-01

    Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003-2010 National Health and Nutrition Examination Survey to quantify diet׳s role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation by multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress

    PubMed Central

    Colacino, Justin A.; Arthur, Anna E.; Ferguson, Kelly K.; Rozek, Laura S.

    2014-01-01

    Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003–2010 National Health and Nutrition Examination Survey to quantify diet’s role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation by multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. PMID:24607659

  9. Biochemical and histological responses of Rattus novergicus (Wistar) infected by Echinostoma paraensei (Trematoda: Echinostomatidae).

    PubMed

    Garcia, Juberlan S; Hooper, Cleber S; Simões, Raquel O; Dos Santos, Marcos Antônio J; Maldonado, Arnaldo; Pinheiro, Jairo

    2011-05-31

    Tests were performed to evaluate the biochemical alterations in Rattus norvegicus after infection by the intestinal trematode Echinostoma paraensei. The rodents received 150 metacercariae each, serum samples were collected and the parasite load was quantified weekly until the fifth week of infection. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALKP), gamma-glutamyl transferase (GGT), bilirubin, glucose, total proteins and fractions and hepatic glycogen were determined. All the animals exposed to the metacercariae were infected in the first week and worms were recovered up to the third week after infection. The levels of AST, ALT, GGT, bilirubin and globulin rose in the first and/or second week and declined thereafter to levels near those of the control group. In contrast, the level of total proteins in the plasma fell significantly in the first week while the ALKP activity went down only in the fourth and fifth weeks in relation to the control group. There was no significant difference in the levels of albumin, glycogen and glucose. Infection by E. paraensei in R. norvegicus causes changes in the hepatic function, possibly resulting from the cholestasis produced by the partial obstruction of the bile duct by the helminths. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Assessing alcohol intake & its dose-dependent effects on liver enzymes by 24-h recall and questionnaire using NHANES 2001-2010 data

    DOE PAGES

    Agarwal, Sanjiv; Fulgoni, III, Victor L.; Lieberman, Harris R.

    2016-06-22

    Alcohol is a significant component of the diet with dose-dependent risks and benefits. High doses of alcohol damage the liver and early symptoms of liver disease include changes in routinely assessed liver enzymes. Less is known regarding the mechanisms responsible for the benefits of moderate alcohol consumption, including their effects on the liver. The objectives of this study were to examine alcohol’s dose-dependent effects on markers of liver function (alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and bilirubin), as well as to compare the different methods of assessing alcohol intake using NHANES 2001–2010 adultmore » data (N =24,807). Three methods were used to estimate alcohol intake from all volunteers: 24-h recall; the National Cancer Institute (NCI) method of usual intake; and a specific alcohol intake questionnaire. Mean alcohol intake by 24-h recall, NCI method and questionnaire was 41.0 ± 0.8 g/d, 10.9 ± 0.2 g/d and 11.0 ± 0.2 g/d, respectively. Alcohol consumers had significantly lower levels of ALP and higher levels of AST, GGT and bilirubin compared to non-consumers (P < 0.01) and activities of ALT, AST, and GGT increased and of ALP decreased as alcohol intake increased, regardless of intake assessment method used. The most sensitive measure of alcohol consumption was GGT. Since alcohol had a graded linear effect on several liver enzymes, including at low and moderate doses, benefits as well as risks of alcohol intake may be related to liver function. In conclusion, since the NCI method and alcohol questionnaire yielded very similar alcohol intake estimates, this study cross-validated these methods and demonstrated the robustness of the NCI method for estimating intake of irregularly consumed foods.« less

  11. Assessing alcohol intake & its dose-dependent effects on liver enzymes by 24-h recall and questionnaire using NHANES 2001-2010 data

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

    Agarwal, Sanjiv; Fulgoni, III, Victor L.; Lieberman, Harris R.

    Alcohol is a significant component of the diet with dose-dependent risks and benefits. High doses of alcohol damage the liver and early symptoms of liver disease include changes in routinely assessed liver enzymes. Less is known regarding the mechanisms responsible for the benefits of moderate alcohol consumption, including their effects on the liver. The objectives of this study were to examine alcohol’s dose-dependent effects on markers of liver function (alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and bilirubin), as well as to compare the different methods of assessing alcohol intake using NHANES 2001–2010 adultmore » data (N =24,807). Three methods were used to estimate alcohol intake from all volunteers: 24-h recall; the National Cancer Institute (NCI) method of usual intake; and a specific alcohol intake questionnaire. Mean alcohol intake by 24-h recall, NCI method and questionnaire was 41.0 ± 0.8 g/d, 10.9 ± 0.2 g/d and 11.0 ± 0.2 g/d, respectively. Alcohol consumers had significantly lower levels of ALP and higher levels of AST, GGT and bilirubin compared to non-consumers (P < 0.01) and activities of ALT, AST, and GGT increased and of ALP decreased as alcohol intake increased, regardless of intake assessment method used. The most sensitive measure of alcohol consumption was GGT. Since alcohol had a graded linear effect on several liver enzymes, including at low and moderate doses, benefits as well as risks of alcohol intake may be related to liver function. In conclusion, since the NCI method and alcohol questionnaire yielded very similar alcohol intake estimates, this study cross-validated these methods and demonstrated the robustness of the NCI method for estimating intake of irregularly consumed foods.« less

  12. Construction of environmental risk score beyond standard linear models using machine learning methods: application to metal mixtures, oxidative stress and cardiovascular disease in NHANES.

    PubMed

    Park, Sung Kyun; Zhao, Zhangchen; Mukherjee, Bhramar

    2017-09-26

    There is growing concern of health effects of exposure to pollutant mixtures. We initially proposed an Environmental Risk Score (ERS) as a summary measure to examine the risk of exposure to multi-pollutants in epidemiologic research considering only pollutant main effects. We expand the ERS by consideration of pollutant-pollutant interactions using modern machine learning methods. We illustrate the multi-pollutant approaches to predicting a marker of oxidative stress (gamma-glutamyl transferase (GGT)), a common disease pathway linking environmental exposure and numerous health endpoints. We examined 20 metal biomarkers measured in urine or whole blood from 6 cycles of the National Health and Nutrition Examination Survey (NHANES 2003-2004 to 2013-2014, n = 9664). We randomly split the data evenly into training and testing sets and constructed ERS's of metal mixtures for GGT using adaptive elastic-net with main effects and pairwise interactions (AENET-I), Bayesian additive regression tree (BART), Bayesian kernel machine regression (BKMR), and Super Learner in the training set and evaluated their performances in the testing set. We also evaluated the associations between GGT-ERS and cardiovascular endpoints. ERS based on AENET-I performed better than other approaches in terms of prediction errors in the testing set. Important metals identified in relation to GGT include cadmium (urine), dimethylarsonic acid, monomethylarsonic acid, cobalt, and barium. All ERS's showed significant associations with systolic and diastolic blood pressure and hypertension. For hypertension, one SD increase in each ERS from AENET-I, BART and SuperLearner were associated with odds ratios of 1.26 (95% CI, 1.15, 1.38), 1.17 (1.09, 1.25), and 1.30 (1.20, 1.40), respectively. ERS's showed non-significant positive associations with mortality outcomes. ERS is a useful tool for characterizing cumulative risk from pollutant mixtures, with accounting for statistical challenges such as high

  13. Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

    PubMed

    Nielsen, H K; Husted, S E; Koopmann, H D; Fasting, H; Simonsen, O; Andersen, K; Husegaard, H C; Petersen, T K

    1984-01-01

    Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

  14. Liraglutide attenuates partial warm ischemia-reperfusion injury in rat livers.

    PubMed

    Abdelsameea, Ahmed A; Abbas, Noha A T; Abdel Raouf, Samar M

    2017-03-01

    Ischemia-reperfusion (IR) injury constitutes the most important cause of primary dysfunction of liver grafts. In this study, we have addressed the possible hepatoprotective action of liraglutide against partial warm hepatic IR injury in male rats. Rats were randomly assigned into: sham, IR, and liraglutide-pretreated IR groups. Liraglutide was administered 50 μg/kg s.c. twice daily for 14 days, and then, hepatic IR was induced by clamping portal vein and hepatic artery to left and median lobes for 30 min followed by reperfusion for 24 h. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities were determined. Malondialdehyde (MDA) level, reduced glutathione (GSH) content, tumor necrosis factor-α (TNF-α), phosphoralated Akt (p-Akt), and caspase-3 levels of the liver were determined. Hematoxylin and eosin (H&E) stained sections from liver were examined as well as immunohistochemical sections for detection of Bcl-2 expression. IR injury increased ALT, AST, and GGT while decreased GSH and p-Akt with increase in MDA, TNF-α, and caspase-3 levels in the liver with necrosis and inflammatory cellular infiltration with decreased Bcl-2 expression. Pretreatment with liraglutide decreased ALT, AST, and GGT activities while increased glutathione content and Akt activation with decrements in MDA, TNF-α, and caspase-3 levels with attenuation of necrosis and inflammation while enhanced Bcl-2 expression in the liver. Liraglutide protects against IR injury of the liver through antiinflammatory and antioxidant actions as well as inhibition of apoptosis.

  15. Modulation of endothelial GSH concentrations: effect of exogenous GSH and GSH monoethyl ester

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

    Tsan, M.F.; White, J.E.; Rosano, C.L.

    We studied the effects of exogenous glutathione (GSH) and GSH monoethyl ester (GSH-MEE) on the enhancement of endothelial GSH concentrations. The preparation of GSH-MEE used contained 91% GSH-MEE, approximately 9% GSH diethyl ester (GSH-DEE) and a trace amount of GSH. Both GSH and GSH-MEE markedly stimulated the intracellular concentrations of GSH in endothelial cells. GSH-MEE was more potent than GSH. The enhancement of endothelial GSH concentration by exogenous GSH was completely inhibited by buthionine sulfoximine (BSO), a potent inhibitor of gamma-glutamylcysteine synthase, or acivicin (AT-125), an inhibitor of gamma-glutamyl transpeptidase, suggesting that it was due to the extracellular breakdown andmore » subsequent intracellular resynthesis of GSH. In contrast, the effect of GSH-MEE was largely resistant to BSO and acivicin, suggesting that it was primarily due to transport of GSH-MEE followed by intracellular hydrolysis. The GSH-MEE preparation, which contained 9% GSH-DEE, at concentrations of 2 mM or higher caused vacuolization of endothelial cells. The enhancement of GSH concentrations by exogenous GSH, but not by GSH-MEE, protected endothelial cells against H/sub 2/O/sub 2/-induced injury.« less

  16. Species differences in hematological values of captive cranes, geese, raptors, and quail

    USGS Publications Warehouse

    Gee, G.F.; Carpenter, J.W.; Hensler, G.L.

    1981-01-01

    Hematological and serum chemical constituents of blood were determined for 12 species, including 7 endangered species, of cranes, geese, raptors, and quail in captivity at the Patuxent Wildlife Research Center. Means, standard deviations, analysis of variance by species and sex, and a series of multiple comparisons of means were derived for each parameter investigated. Differences among some species means were observed in all blood parameters except gamma-glutamyl transpeptidase. Although sampled during the reproductively quiescent period, an influence of sex was noted in red blood cell count, hemoglobin, albumin, glucose, cholesterol, serum glutamic oxaloacetic transaminase, Ca, and P. Our data and values reported in literature indicate that most hematological parameters vary among species and, in some cases, according to methods used to determine them. Therefore, baseline data for captive and wild birds should be established by using standard methods, and should be made available to aid others for use in assessing physiological and pathological conditions of these species.

  17. Higher ferritin levels, but not serum iron or transferrin saturation, are associated with Type 2 diabetes mellitus in adult men and women free of genetic haemochromatosis.

    PubMed

    Yeap, Bu B; Divitini, Mark L; Gunton, Jenny E; Olynyk, John K; Beilby, John P; McQuillan, Brendan; Hung, Joseph; Knuiman, Matthew W

    2015-04-01

    Iron overload predisposes to diabetes and higher ferritin levels have been associated with diabetes. However, it is unclear whether ferritin reflects differences in iron-related parameters between diabetic and nondiabetic persons. We examined associations of serum ferritin, iron and transferrin saturation with Type 2 diabetes in adults without genetic predisposition to iron overload. Cross-sectional analysis of community-dwelling men and women aged 17-97 years from the Busselton Health Survey, Western Australia. Men and women carrying genotypes associated with haemochromatosis (C282Y/C282Y or C282Y/H63D) were excluded. Serum ferritin, iron and transferrin saturation were assayed. There were 1834 men (122 with diabetes, 6·6%) and 2351 women (141 with diabetes, 6%). In men, higher serum ferritin was associated with diabetes after adjusting for age, smoking, alcohol, cardiovascular history, body mass index (BMI), waist, blood pressure, lipids, C-reactive protein (CRP), adiponectin, alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) [odds ratio (OR): 1·29 per 1 unit increase log ferritin, 95% confidence interval (CI) = 1·01-1·65, P = 0·043]. In women, higher serum ferritin was associated with diabetes [fully adjusted OR: 1·31 per 1 unit increase log ferritin, 95% CI = 1·04-1·63, P = 0·020; 1·84 for tertile (T) 3 vs T1, 95% CI = 1·09-3·11]. Neither iron levels nor transferrin saturation were associated with diabetes risk in men or women. Higher ferritin was not associated with insulin resistance in nondiabetic adults. In adults, higher ferritin levels are independently associated with prevalent diabetes while iron and transferrin saturation are not. Ferritin is a robust biomarker for diabetes risk, but further investigation is needed to clarify whether this relationship is mediated via iron metabolism. © 2014 John Wiley & Sons Ltd.

  18. Protective effect of Ocimum sanctum on 3-methylcholanthrene, 7,12-dimethylbenz(a)anthracene and aflatoxin B1 induced skin tumorigenesis in mice

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

    Rastogi, Shipra; Shukla, Yogeshwer; Paul, Bhola N.

    A study on the protective effect of alcoholic extract of the leaves of Ocimum sanctum on 3-mthylcholanthrene (MCA), 7,12-dimethylbenzanthracene (DMBA) and aflatoxin B{sub 1} (AFB{sub 1}) induced skin tumorigenesis in a mouse model has been investigated. The study involved pretreatment of mice with the leaf extract prior to either MCA application or tetradecanoyl phorbol acetate (TPA) treatment in a two-stage tumor protocol viz a viz, DMBA/TPA and AFB1/TPA. The results of the present study indicate that the pretreatment with alcoholic extract of the leaves of O. sanctum decreased the number of tumors in MCA, DMBA/TPA and AFB1/TPA treated mice. Themore » skin tumor induced animals pretreated with alcoholic extract led to a decrease in the expression of cutaneous {gamma}-glutamyl transpeptidase (GGT) and glutathione-S-transferase-P (GST-P) protein. The histopathological examination of skin tumors treated with leaf extract showed increased infiltration of polymorphonuclear, mononuclear and lymphocytic cells, decreased ornithine decarboxylase activity with concomitant enhancement of interleukin-1{beta} (IL-1{beta}) and tumor necrosis factor-{alpha} (TNF-{alpha}) in the serum, implying the in vivo antiproliferative and immunomodulatory activity of leaf extract. The decrease in cutaneous phase I enzymes and elevation of phase II enzymes in response to topical application of leaf extract prior to MCA, AFB1, DMBA/TPA and AFB1/TPA treatment indicate the possibility of impairment in reactive metabolite(s) formation and thereby reducing skin carcinogenicity. Furthermore, pretreatment of leaf extract in the carcinogen induced animals resulted in elevation of glutathione levels and decrease in lipid peroxidation along with heat shock protein expression, indicating a scavenging or antioxidant potential of the extract during chemical carcinogenesis. Thus it can be concluded that leaf extract of O. sanctum provides protection against chemical carcinogenesis in one or more of the

  19. The γ-Glutamyl Cycle in the Choroid Plexus: Its Possible Function in Amino Acid Transport

    PubMed Central

    Tate, Suresh S.; Ross, Leonard L.; Meister, Alton

    1973-01-01

    Various anatomic regions of rabbit brain have been examined for activities of the enzymes of the γ-glutamyl cycle. While these enzyme activities were widely distributed in the brain, they are present in much higher concentrations in the choroid plexus than in other parts of the brain. The activities observed are of about the same order of magnitude as found in the kidney. These observations and other considerations suggest that the γ-glutamyl cycle may play a significant role in the transport of amino acids between blood and cerebrospinal fluid. PMID:4145786

  20. Immunochemical detection of glycated beta- and gamma-crystallins in lens and their circulating autoantibodies (IgG) in streptozocin induced diabetic rat.

    PubMed

    Ranjan, Mala; Nayak, Sujatha; Rao, Beedu Sashidhar

    2006-09-13

    This study used an immunochemical approach aimed to detect the glycated crystallins (beta- and gamma-crystallin) in rat lens and their circulating specific autoantibodies in serum during the course of cataractogenesis. Streptozocin (STZ; 55 mg/kg body mass) induced diabetic male Wistar/NIN rats (2-3 months old) and control nondiabetic rats were used for this study. Plasma glucose, glycated hemoglobin and body weight were evaluated on day zero, and at the interval of every two weeks up to the eighth week of post-injection in both the groups. Other biochemical parameters, such as the levels of nonprotein sulfhydryl (-SH) groups and the activity of gamma-glutamyl transpeptidase (gamma-GT) in lens proteins were also estimated. Cataract progress was monitored by measuring the advanced glycation end product (AGE)-like fluorophores in both intact lens as well as in lens homogenate employing digital based image analysis and spectrofluorimetric methods. Similarly, the polyclonal antibodies specific to beta-glycated-, gamma-glycated-, beta-, and gamma-crystallins were used to determine the concentration of respective immunogens in lens by noncompetitive ELISA and their respective circulating antibodies by antibody capture assay. The profile of glycated lens protein (soluble and insoluble fractions) during the course of cataractogenesis was assessed by the western blot technique. STZ induced diabetic rats showed typical signs of diabetes (hyperglycemia, increased water and food intake with no increase in body weight). Biochemical analysis of total lens protein showed a significant (p = <0.001) decrease in the levels of nonprotein -SH groups. The activity of lenticular gamma-GT in diabetic rats was found to be unaltered as compared to the control group. Digital analysis of intact lens illustrated a positive correlation (r(2)=0.888) with the formation of AGE-like fluorophores during the course of cataractogenesis. A similar trend was also observed in the levels of AGE

  1. A γ-glutamyl cyclotransferase protects Arabidopsis plants from heavy metal toxicity by recycling glutamate to maintain glutathione homeostasis.

    PubMed

    Paulose, Bibin; Chhikara, Sudesh; Coomey, Joshua; Jung, Ha-Il; Vatamaniuk, Olena; Dhankher, Om Parkash

    2013-11-01

    Plants detoxify toxic metals through a GSH-dependent pathway. GSH homeostasis is maintained by the γ-glutamyl cycle, which involves GSH synthesis and degradation and the recycling of component amino acids. The enzyme γ-glutamyl cyclotransferase (GGCT) is involved in Glu recycling, but the gene(s) encoding GGCT has not been identified in plants. Here, we report that an Arabidopsis thaliana protein with a cation transport regulator-like domain, hereafter referred to as GGCT2;1, functions as γ-glutamyl cyclotransferase. Heterologous expression of GGCT2;1 in Saccharomyces cerevisiae produced phenotypes that were consistent with decreased GSH content attributable to either GSH degradation or the diversion of γ-glutamyl peptides to produce 5-oxoproline (5-OP). 5-OP levels were further increased by the addition of arsenite and GSH to the medium, indicating that GGCT2;1 participates in the cellular response to arsenic (As) via GSH degradation. Recombinant GGCT2;1 converted both GSH and γ-glutamyl Ala to 5-OP in vitro. GGCT2;1 transcripts were upregulated in As-treated Arabidopsis, and ggct2;1 knockout mutants were more tolerant to As and cadmium than the wild type. Overexpression of GGCT2;1 in Arabidopsis resulted in the accumulation of 5-OP. Under As toxicity, the overexpression lines showed minimal changes in de novo Glu synthesis, while the ggct2;1 mutant increased nitrogen assimilation by severalfold, resulting in a very low As/N ratio in tissue. Thus, our results suggest that GGCT2;1 ensures sufficient GSH turnover during abiotic stress by recycling Glu.

  2. Comparison of the effects of metoprolol or carvedilol on serum gamma-glutamyltransferase and uric acid levels among patients with acute coronary syndrome without ST segment elevation.

    PubMed

    Aşkın, Lütfü; Karakelleoğlu, Şule; Değirmenci, Hüsnü; Demirelli, Selami; Şimşek, Ziya; Taş, Muhammed Hakan; Topçu, Selim; Lazoğlu, Zakir

    2016-01-01

    Serum gamma-glutamyltransferase (GGT) and uric acid levels measured in patients with acute coronary syndrome without ST segment elevation (NSTEMI) are important in diagnosis and in predicting the prognosis of the disease. There is a limited number of clinical studies investigating the effects of beta-blockers on GGT and uric acid levels in these patients. In our study, we aimed to investigate the effects of beta-blocker therapy on GGT and uric acid levels. We conducted a randomized, prospective clinical study. Hundred patients with NSTEMI were included in this study, and they were divided into two groups. Fifty patients were administered metoprolol succinate treatment (1 x 50 mg), whereas the remaining 50 patients were administered carvedilol treatment (2 x 12.5 mg). Thereafter, all of the patients underwent coronary angiography. Blood samples were taken at the time of admission, at the 1st month, and 3rd month to detect GGT and uric acid levels. There was no statistically significant difference among the metoprolol or carvedilol groups in terms of the GGT levels measured at the baseline, 1st month, and 3rd month (p=0.904 and p=0.573, respectively). In addition, there was no statistically significant difference among the metoprolol or carvedilol groups in terms of uric acid levels measured at the baseline, 1st month, and 3rd month (p=0.601 and p=0.601, respectively). We found that GGT and uric acid levels did not show any change compared to the baseline values, with metoprolol and carvedilol treatment initiated in the early period in patients with NSTEMI.

  3. Crystallization and preliminary crystallographic analysis of the transpeptidase domain of penicillin-binding protein 2B from Streptococcus pneumoniae

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

    Yamada, Mototsugu, E-mail: mototsugu-yamada@meiji.co.jp; Watanabe, Takashi; Baba, Nobuyoshi

    The selenomethionyl-substituted transpeptidase domain of penicillin-binding protein (PBP) 2B from S. pneumoniae was isolated from a limited proteolysis digest of the soluble form of recombinant PBP 2B and then crystallized. MAD data were collected to 2.4 Å resolution. Penicillin-binding protein (PBP) 2B from Streptococcus pneumoniae catalyzes the cross-linking of peptidoglycan precursors that occurs during bacterial cell-wall biosynthesis. A selenomethionyl (SeMet) substituted PBP 2B transpeptidase domain was isolated from a limited proteolysis digest of a soluble form of recombinant PBP 2B and then crystallized. The crystals belonged to space group P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 86.39,more » c = 143.27 Å. Diffraction data were collected to 2.4 Å resolution using the BL32B2 beamline at SPring-8. The asymmetric unit contains one protein molecule and 63.7% solvent.« less

  4. Gamma-glutamyltransferase activity and development of the metabolic syndrome (International Diabetes Federation Definition) in middle-aged men and women: Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort.

    PubMed

    André, Philippe; Balkau, Beverley; Vol, Sylviane; Charles, Marie Aline; Eschwège, Eveline

    2007-09-01

    Among hepatic enzymes, gamma-glutamyltransferase (GGT) is the main predictor of type 2 diabetes incidence, although it has not been shown that GGT predicts pre-diabetes states. Our aim was to study the association of GGT with the development of the metabolic syndrome (MetS). We analyzed the 3-year data from the Data from Epidemiological Study on the Insulin Resistance Syndrome prospective cohort of 1,656 men and 1,889 women without MetS at baseline, according to the International Diabetes Federation definition. Over 3 years, 309 participants developed the MetS. After adjustment for age, alcohol intake, physical activity, smoking habits, and alanine aminotransferase (ALT), the odds ratios for incident MetS increased across baseline GGT quartiles (1, 1.96, 2.25, and 3.81 in men, P < 0.03; and 1, 1.23, 1.80, and 1.58 in women, P < 0.05). After additional adjustment for insulin resistance markers (fasting insulin or homeostasis model assessment of insulin resistance index), the association was attenuated and the linear relation no longer significant in both sexes (P = 0.08, P = 0.16). However, men in the highest in comparison to the lowest quartile of GGT retained a significant risk for incident MetS. In women, there was no longer a significant risk. GGT was significantly associated with the 3-year incidence of individual components of the MetS. The incidence of the MetS also increased with ALT, but after adjustment on GGT this association remained significant only in women. GGT, a predictor of type 2 diabetes, was associated with a risk of incident MetS. This association was mainly related with insulin resistance but was independent of other confounding factors.

  5. Diagnostic value and clinical laboratory associations of antibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in a Caucasian cohort with systemic lupus erythematosus.

    PubMed

    Barkhudarova, Fidan; Dähnrich, Cornelia; Rosemann, Anke; Schneider, Udo; Stöcker, Winfried; Burmester, Gerd-Rüdiger; Egerer, Karl; Schlumberger, Wolfgang; Hiepe, Falk; Biesen, Robert

    2011-02-10

    In this study, we sought to determine the diagnostic value and clinical laboratory associations of autoantibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in systemic lupus erythematosus (SLE). Autoantibodies against recombinant ribosomal P proteins (aRibPR0, aRibPR1 and aRibPR2) and antibodies against native ribosomal P heterocomplex (aRibPNH) were determined in sera from patients with SLE (n = 163), systemic sclerosis (n = 66), Sjögren's syndrome (n = 54), rheumatoid arthritis (n = 90) and healthy donors (n = 100) using enzyme-linked immunosorbent assay. Test results were correlated to medical records, including the American College of Rheumatology criteria, the Systemic Lupus Erythematosus Disease Activity Index 2000, laboratory data and medications of all SLE patients. Sensitivities of 22.0% for aRibPR0, 14.9% for aRibPR2, 14.3% for aRibPNH and 10.7% for aRibPR1 were obtained at a specificity of 99%. The assay for aRibPR0 detection demonstrated the best performance in receiver-operating characteristics analysis, with aRibPR0 detectable in 10% of anti-Smith antibody and anti-double-stranded DNA-negative sera at a specificity of 100%. ARibPR0 positivity was associated with lymphocytopenia. ARibPR1+ patients had significantly higher γ-glutamyl transpeptidase (GGT) levels than their aRibPR1- counterparts. No specific damage occurred in aRibP+ lupus patients compared with a group of age-, sex- and nephritis-matched aRibP- lupus patients within 3 years. The determination of antibodies against ribosomal P proteins improves the diagnosis of SLE and should therefore be implemented in upcoming criteria for the diagnosis or classification of SLE. High titers of aRibPR0 can be associated with lymphocytopenia, and high titers of aRibPR1 can be associated with elevated GGT levels. So far, there is no evidence for a prognostic value of aRibPs for damage.

  6. Assessment of non-invasive models for liver fibrosis in chronic hepatitis B virus related liver disease patients in resource limited settings.

    PubMed

    Shrivastava, Rakesh; Sen, Sourav; Banerji, Debabrata; Praharaj, Ashok K; Chopra, Gurvinder Singh; Gill, Satyajit Singh

    2013-01-01

    A total of 350 million individuals are affected by chronic hepatitis B virus infection world-wide. Historically, liver biopsy has been instrumental in adequately assessing patients with chronic liver disease. A number of non-invasive models have been studied world-wide. The aim of this study is to assess the utility of non-invasive mathematical models of liver fibrosis in chronic hepatitis B (CHB). Indian patients in a resource limited setting using routinely performed non-invasive laboratory investigations. A cross-sectional study carried out at a tertiary care center. A total of 52 consecutive chronic liver disease patients who underwent percutaneous liver biopsy and 25 healthy controls were enrolled in the study. Routine laboratory investigations included serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gama glutamyl transpeptidase (GGT), total bilirubin, total cholesterol, prothrombin time and platelet count. Three non-invasive models for namely aspartate aminotransferase to platelet ratio index (APRI), Fibrosis 4 (FIB-4) and Forn's index were calculated. Outcomes were compared for the assessment of best predictor of fibrosis by calculating the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each index. Medcalc online software and by Microsoft Excel Worksheet. Chi-square test was used for significance. P value < 0.05 was taken as significant. While the serum levels of AST, ALT and GGT were significantly higher in patients group as compare with the healthy controls (P < 0.01), the platelet counts were significantly lower in patient group as compared to the control group (P < 0.01). Mean value of all 3 indices were significantly higher in patients group as compare with the controls (P < 0.01). Out of the three indices, APRI index with a NPV of 95% appeared to be a better model for excluding significant liver fibrosis while FIB-4 with a PPV of 61% showed fair correlation with significant

  7. tRNAGlu increases the affinity of glutamyl-tRNA synthetase for its inhibitor glutamyl-sulfamoyl-adenosine, an analogue of the aminoacylation reaction intermediate glutamyl-AMP: mechanistic and evolutionary implications.

    PubMed

    Blais, Sébastien P; Kornblatt, Jack A; Barbeau, Xavier; Bonnaure, Guillaume; Lagüe, Patrick; Chênevert, Robert; Lapointe, Jacques

    2015-01-01

    For tRNA-dependent protein biosynthesis, amino acids are first activated by aminoacyl-tRNA synthetases (aaRSs) yielding the reaction intermediates aminoacyl-AMP (aa-AMP). Stable analogues of aa-AMP, such as aminoacyl-sulfamoyl-adenosines, inhibit their cognate aaRSs. Glutamyl-sulfamoyl-adenosine (Glu-AMS) is the best known inhibitor of Escherichia coli glutamyl-tRNA synthetase (GluRS). Thermodynamic parameters of the interactions between Glu-AMS and E. coli GluRS were measured in the presence and in the absence of tRNA by isothermal titration microcalorimetry. A significant entropic contribution for the interactions between Glu-AMS and GluRS in the absence of tRNA or in the presence of the cognate tRNAGlu or of the non-cognate tRNAPhe is indicated by the negative values of -TΔSb, and by the negative value of ΔCp. On the other hand, the large negative enthalpy is the dominant contribution to ΔGb in the absence of tRNA. The affinity of GluRS for Glu-AMS is not altered in the presence of the non-cognate tRNAPhe, but the dissociation constant Kd is decreased 50-fold in the presence of tRNAGlu; this result is consistent with molecular dynamics results indicating the presence of an H-bond between Glu-AMS and the 3'-OH oxygen of the 3'-terminal ribose of tRNAGlu in the Glu-AMS•GluRS•tRNAGlu complex. Glu-AMS being a very close structural analogue of Glu-AMP, its weak binding to free GluRS suggests that the unstable Glu-AMP reaction intermediate binds weakly to GluRS; these results could explain why all the known GluRSs evolved to activate glutamate only in the presence of tRNAGlu, the coupling of glutamate activation to its transfer to tRNA preventing unproductive cleavage of ATP.

  8. tRNAGlu Increases the Affinity of Glutamyl-tRNA Synthetase for Its Inhibitor Glutamyl-Sulfamoyl-Adenosine, an Analogue of the Aminoacylation Reaction Intermediate Glutamyl-AMP: Mechanistic and Evolutionary Implications

    PubMed Central

    Blais, Sébastien P.; Kornblatt, Jack A.; Barbeau, Xavier; Bonnaure, Guillaume; Lagüe, Patrick; Chênevert, Robert; Lapointe, Jacques

    2015-01-01

    For tRNA-dependent protein biosynthesis, amino acids are first activated by aminoacyl-tRNA synthetases (aaRSs) yielding the reaction intermediates aminoacyl-AMP (aa-AMP). Stable analogues of aa-AMP, such as aminoacyl-sulfamoyl-adenosines, inhibit their cognate aaRSs. Glutamyl-sulfamoyl-adenosine (Glu-AMS) is the best known inhibitor of Escherichia coli glutamyl-tRNA synthetase (GluRS). Thermodynamic parameters of the interactions between Glu-AMS and E. coli GluRS were measured in the presence and in the absence of tRNA by isothermal titration microcalorimetry. A significant entropic contribution for the interactions between Glu-AMS and GluRS in the absence of tRNA or in the presence of the cognate tRNAGlu or of the non-cognate tRNAPhe is indicated by the negative values of –TΔSb, and by the negative value of ΔCp. On the other hand, the large negative enthalpy is the dominant contribution to ΔGb in the absence of tRNA. The affinity of GluRS for Glu-AMS is not altered in the presence of the non-cognate tRNAPhe, but the dissociation constant K d is decreased 50-fold in the presence of tRNAGlu; this result is consistent with molecular dynamics results indicating the presence of an H-bond between Glu-AMS and the 3’-OH oxygen of the 3’-terminal ribose of tRNAGlu in the Glu-AMS•GluRS•tRNAGlu complex. Glu-AMS being a very close structural analogue of Glu-AMP, its weak binding to free GluRS suggests that the unstable Glu-AMP reaction intermediate binds weakly to GluRS; these results could explain why all the known GluRSs evolved to activate glutamate only in the presence of tRNAGlu, the coupling of glutamate activation to its transfer to tRNA preventing unproductive cleavage of ATP. PMID:25860020

  9. Structural and biochemical analyses of a Clostridium perfringens sortase D transpeptidase

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

    Suryadinata, Randy, E-mail: randy.suryadinata@csiro.au; Seabrook, Shane A.; Adams, Timothy E.

    The structure of C. perfringens sortase D was determined at 1.99 Å resolution. Comparative biochemical and structural analyses revealed that this transpeptidase may represent a new subclass of the sortase D family. The assembly and anchorage of various pathogenic proteins on the surface of Gram-positive bacteria is mediated by the sortase family of enzymes. These cysteine transpeptidases catalyze a unique sorting signal motif located at the C-terminus of their target substrate and promote the covalent attachment of these proteins onto an amino nucleophile located on another protein or on the bacterial cell wall. Each of the six distinct classes ofmore » sortases displays a unique biological role, with sequential activation of multiple sortases often observed in many Gram-positive bacteria to decorate their peptidoglycans. Less is known about the members of the class D family of sortases (SrtD), but they have a suggested role in spore formation in an oxygen-limiting environment. Here, the crystal structure of the SrtD enzyme from Clostridium perfringens was determined at 1.99 Å resolution. Comparative analysis of the C. perfringens SrtD structure reveals the typical eight-stranded β-barrel fold observed in all other known sortases, along with the conserved catalytic triad consisting of cysteine, histidine and arginine residues. Biochemical approaches further reveal the specifics of the SrtD catalytic activity in vitro, with a significant preference for the LPQTGS sorting motif. Additionally, the catalytic activity of SrtD is most efficient at 316 K and can be further improved in the presence of magnesium cations. Since C. perfringens spores are heat-resistant and lead to foodborne illnesses, characterization of the spore-promoting sortase SrtD may lead to the development of new antimicrobial agents.« less

  10. [Relationship between phenotype and genotype of ABCB11 deficiency in siblings and literature review].

    PubMed

    Peng, X R; Lu, Y; Zhang, M H; Li, L T; Xie, X B; Gong, J Y; Wang, J S

    2018-06-02

    Objective: To explore the relationship between genotype and phenotype of ABCB11 deficiency. Methods: Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene' or 'bile salt export pump', 'cholestasis' and 'child' as key words. Results: The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after

  11. Metabolic changes and induction of hepatic lipidosis during feed restriction in llamas.

    PubMed

    Tornquist, S J; Cebra, C K; Van Saun, R J; Smith, B B; Mattoon, J S

    2001-07-01

    To determine whether feed restriction induces hepatic lipidosis (HL) in llamas and to evaluate the metabolic changes that develop during feed restriction. 8 healthy adult female llamas. Llamas were fed grass hay at a rate of 0.25% of their body weight per day for 13 to 28 days. Llamas were monitored by use of clinical observation, serum biochemical analyses, and ultrasound-guided liver biopsies. All 8 llamas lost weight and mobilized fat. Five llamas developed HL, including 4 that were nursing crias. During the period of feed restriction, mean serum concentration of bile acids and activities of aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), and gamma-glutamyl transferase (GGT) were significantly higher in llamas that developed HL, compared with llamas that did not. Mean insulin-to-cortisol concentration ratios were lower in llamas with HL before and up to 7 days of feed restriction, compared with those that did not develop HL. HL in llamas may be induced by severe feed restriction, particularly in the face of increased energy demand. Llamas with weight loss attributable to inadequate dietary intake may develop biochemical evidence of hepatopathy and HL. Increases in serum concentration of bile acids and activities of GGT, AST, and SDH may indicate the development of HL in llamas and identify affected animals for aggressive therapeutic intervention.

  12. Effects of Multivitamin, Multimineral and Phytonutrient Supplementation on Nutrient Status and Biomarkers of Heart Health Risk in a Russian Population: A Randomized, Double Blind, Placebo Controlled Study.

    PubMed

    Isakov, Vasily A; Bogdanova, Alexandra A; Bessonov, Vladimir V; Sentsova, Tatiana B; Tutelyan, Victor A; Lin, Yumei; Kazlova, Valentina; Hong, Jina; Velliquette, Rodney A

    2018-01-25

    The primary objective of this clinical study was to evaluate the effect of a dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood nutrient status and biomarkers of heart health risk in a Russian population. One hundred twenty healthy adults (40-70 years) were recruited for a 56-day (eight-week) randomized, double blind, placebo controlled study with parallel design. Subjects were divided into two groups and received either a VMP or a placebo (PLA) supplement. Blood nutrient levels of β-carotene, α-tocopherol, vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured at baseline and on Days 28 and 56, and quercetin was measured at baseline and on Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl transferase (GGT), uric acid and blood lipid profile, were measured at baseline and Day 56. Dietary VMP supplementation for 56 days significantly increased circulating levels of quercetin, vitamin C, RBC folate and partially prevented the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were significantly reduced (-3.97 ± 10.09 µmol/L; -1.68 ± 14.53 U/L, respectively) after VMP supplementation compared to baseline. Dietary VMP supplementation improved the nutrient status and reduced biomarkers of heart health risk in a Russian population.

  13. Examination of the relationships between environmental exposures to volatile organic compounds and biochemical liver tests: application of canonical correlation analysis.

    PubMed

    Liu, Jing; Drane, Wanzer; Liu, Xuefeng; Wu, Tiejian

    2009-02-01

    This study was to explore the relationships between personal exposure to 10 volatile organic compounds (VOCs) and biochemical liver tests with the application of canonical correlation analysis. Data from a subsample of the 1999-2000 National Health and Nutrition Examination Survey were used. Serum albumin, total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) served as the outcome variables. Personal exposures to benzene, chloroform, ethylbenzene, tetrachloroethene, toluene, trichloroethene, o-xylene, m-,p-xylene, 1,4-dichlorobenzene, and methyl tert-butyl ether (MTBE) were assessed through the use of passive exposure monitors worn by study participants. The first two canonical correlations were 0.3218 and 0.2575, suggesting a positive correlation mainly between the six VOCs (benzene, ethylbenzene, toluene, o-xylene, m-,p-xylene, and MTBE) and the three biochemical liver tests (albumin, ALP, and GGT) and a positive correlation mainly between the two VOCs (1,4-dichlorobenzene and tetrachloroethene) and the two biochemical liver tests (LDH and TB). Subsequent multiple linear regressions show that exposure to benzene, toluene, or MTBE was associated with serum albumin, while exposure to tetrachloroethene was associated with LDH and total bilirubin. In conclusion, exposure to certain VOCs as a group or individually may influence certain biochemical liver test results in the general population.

  14. The serum level of soluble CD26/dipeptidyl peptidase 4 increases in response to acute hyperglycemia after an oral glucose load in healthy subjects: association with high-molecular weight adiponectin and hepatic enzymes.

    PubMed

    Aso, Yoshimasa; Terasawa, Tomoko; Kato, Kanako; Jojima, Teruo; Suzuki, Kunihiro; Iijima, Toshie; Kawagoe, Yoshiaki; Mikami, Shigeru; Kubota, Yoshiro; Inukai, Toshihiko; Kasai, Kikuo

    2013-11-01

    A soluble form of CD26/dipeptidyl peptidase 4 (sCD26/DPP4) is found in serum and it has DPP4 enzymatic activity. We investigated whether the serum level of sCD26/DPP4 was influenced by the oral glucose tolerance test (OGTT) in healthy subjects. The serum sCD26/DPP4 level increased significantly from 824.5 ng/mL (interquartile range, from 699.0 to 1050 ng/mL) at baseline to a peak of 985.0 ng/mL (interquartile range, from 796.5 to 1215 ng/mL) during the OGTT (P < 0.0001). The peak sCD26/DPP4 level correlated positively with the baseline age and body mass index, and fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), alanine aminotransferase, and γ-glutamyl transpeptidase (GGT) levels whereas it correlated negatively with high-density lipoprotein (HDL) cholesterol and the serum levels of total and high-molecular weight (HMW) adiponectin. Stepwise regression analysis was done with forward selection of variables, including age, FPG, HOMA-IR, TG, HDL cholesterol, uric acid, GGT, C-reactive protein, and HMW adiponectin. In a model that explained 57.5% of the variation of the peak sCD26/DPP4 level, GGT (β = 0.382, P = 0.007) and HOMA-IR (β = 0.307, P = 0.034) were independent determinants of the peak serum level of sCD26/DPP4. Serum HMW adiponectin decreased significantly from 4.43 μg/mL (interquartile range, from 2.80 to 6.65 μg/mL) at baseline to 4.17 μg/mL (interquartile range, from 2.48 to 6.96 μg/mL) 120 minutes after the oral glucose load (P < 0.0001). The baseline serum level of sCD26/DPP4 showed a significant negative correlation with the percent change of HMW adiponectin during the OGTT. In conclusion, the serum level of sCD26/DPP4 increased acutely after an oral glucose load in apparently healthy subjects. The abrupt increase of serum sCD26/DPP4 after a glucose load may be a marker of insulin resistance that could come from liver or muscle. Copyright © 2013 Mosby, Inc. All rights

  15. Effects of non-starch polysaccharides enzymes on pancreatic and small intestinal digestive enzyme activities in piglet fed diets containing high amounts of barley.

    PubMed

    Li, Wei-Fen; Feng, Jie; Xu, Zi-Rong; Yang, Cai-Mei

    2004-03-15

    To investigate effects of non-starch polysaccharides(NSP) enzymes on pancreatic and small intestinal digestive enzyme activities in piglet fed diets containing high amounts of barley. Sixty crossbred piglets averaging 13.5 kg were randomly assigned to two treatment groups with three replications (pens) based on sex and mass. Each group was fed on the diet based on barley with or without added NSP enzymes (0.15%) for a 40-d period. At the end of the experiment the pigs were weighed. Three piglets of each group were chosen and slaughtered. Pancreas, digesta from the distal end of the duodenum and jejunal mucosa were collected for determination. Activities of the digestive enzymes trypsin, chymotrypsin, amylase and lipase were determined in the small intestinal sections as well as in homogenates of pancreatic tissue. Maltase, sucrase, lactase and gamma-glutamyl transpeptidase (gamma-GT) activities were analyzed in jejunal mucosa. Supplementation with NSP enzymes improved growth performance of piglets. It showed that NSP enzymes had no effect on digestive enzyme activities in pancreas, but decreased the activities of proteolytic enzyme, trypsin, amylase and lipase in duodenal contents by 57.56%, 76.08%, 69.03% and 40.22%(P<0.05) compared with control, and increased gamma-GT activities in jejunal mucosa by 118.75%(P<0.05). Supplementation with NSP enzymes in barley based diets could improve piglets' growth performance, decrease activities of proteolytic enzyme, trypsin, amylase and lipase in duodenal contents and increase gamma-GT activities in jejunal mucosa.

  16. Blood biochemistry reference values for wild juvenile loggerhead sea turtles (Caretta caretta) from Madeira archipelago.

    PubMed

    Delgado, Cláudia; Valente, Ana; Quaresma, Isabel; Costa, Margarida; Dellinger, Thomas

    2011-07-01

    Standard biochemical parameters were determined in wild juvenile loggerhead sea turtles Caretta caretta living offshore Madeira Island, northeast Atlantic. We analyzed the influence of age, sex, sea surface temperature, and body condition index on biochemical parameters including uric acid, total bilirubin, total cholesterol, creatinine kinase (CK), glucose, total protein, urea nitrogen, lactate dehydrogenase, aspartate aminotranspherase (AST), gamma-glutamyl transferase (GGT), albumin, alkaline phosphatase (ALP), sodium (NA), potassium (K), chloride, calcium, phosphorus, and magnesium. Significant positive correlations were found between turtle body size and total cholesterol, total protein, and albumin. Total protein and the enzymes AST and CK were lower than reported levels in adults. Calcium levels were lower than those reported in adult or captive turtles, but similar to wild juveniles from Australian waters, and were interpreted as normal for this age category. These data may be useful to evaluate the health status of stranded or injured animals and to improve veterinary care at rehabilitation centers.

  17. The 148 M allele of the PNPLA3 is associated with plasma irisin levels in a population sample of Caucasian children: The PANIC Study.

    PubMed

    Viitasalo, Anna; Atalay, Mustafa; Pihlajamäki, Jussi; Jääskeläinen, Jarmo; Korkmaz, Ayhan; Kaminska, Dorota; Lindi, Virpi; Lakka, Timo A

    2015-07-01

    There are no previous data on the association of PNPLA3 I148M polymorphism (rs738409) with circulating adipokines and myokines in children. Subjects were a population sample of 481 Caucasian children aged 6-8 years. We assessed circulating levels of irisin together with IL-6, TNF-α, leptin, high molecular weight (HMW)-adiponectin, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) while the subjects were stratified according to PNPLA3 I148M variants. The PNPLA3 rs738409 polymorphism had a linear relationship with plasma levels of irisin after adjustment for age, sex and body height (p=0.007) but it was not associated with circulating levels of interleukin- 6 (IL-6), tumor-necrosis factor α (TNF-α), leptin or HMW-adiponectin. PNPLA3 148M allele carriers had higher plasma levels of irisin than the non-carriers. This might be due to compensatory mechanism to limit early steatotic and inflammatory changes in the liver. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Effect of Peppermint Oil on Serum Lipid Peroxidation and Hepatic Enzymes after Immobility Stress in Mice

    PubMed Central

    Marjani, Abdoljalal; Rahmati, Reza; Mansourian, Azad Reza; Veghary, Gholamreza

    2012-01-01

    This study was undertaken to determine the influences of various doses of peppermint oil on the hepatic en-zymes, alanine transaminase, apartate tranaminase, alkaline phosphotase and gamma glutamyl transferase and the level of malondialdehyde in the serum of mice with and without immobility stress. The mice exposed to drink water, 0.9, 27 and 60 mg/kg peppermint oil from the days 1 to 5 for a period of 4 h before and after immobility stress. Serum MDA in-creased in treatment group II, III and IV after immobility stress. There was a significant decrease in ALT in treatment group III and IV after immobility stress. There were also significant decreases in ALP and GGT in treatment group IV af-ter immobility stress. This result may suggest that, MDA level is higher in immobilization stress group than in the un-immobilized animals in serum and this results show that enzyme activities decreased after immobilization stress. PMID:22654997

  19. Primary photosensitization in cattle caused by Froelichia humboldtiana.

    PubMed

    Souza, Paulo E C; Oliveira, Samuel S; Aguiar-Filho, Cristiano R; Cunha, Ana L B; Albuquerque, Raquel F; Evêncio-Neto, Joaquim; Riet-Correa, Franklin; Mendonça, Fábio S

    2012-12-01

    Three outbreaks of primary photosensitization caused by Froelichia humboldtiana are reported in the semiarid region of the states of Pernambuco and Paraíba, in northeastern Brazil. The disease occurred from March to June 2011, affecting 27 bovines out of a total of 70. The main lesions consisted of dermatitis of the white skin, with edema and necrosis. All the bovines recovered after removal from the areas invaded by F. humboldtiana. To produce the disease experimentally, one bovine with white skin was placed for 14 days into an area with F. humboldtiana as the sole forage. This bovine presented photodermatitis on the third day of consumption. The serum concentrations of total, indirect, and conjugated bilirubin and the serum activities of gamma-glutamyl transferase (GGT) and aspartate-aminotransferase (AST) in the spontaneously affected cattle and in the experimental cattle remained within normal ranges. It is concluded that F. humboldtiana causes primary photosensitization in cattle in northeastern Brazil. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. EFFICIENCY OF BORAGE SEEDS OIL AGAINST GAMMA IRRADIATION-INDUCED HEPATOTOXICITY IN MALE RATS: POSSIBLE ANTIOXIDANT ACTIVITY.

    PubMed

    Khattab, Hala A H; Abdallah, Inas Z A; Yousef, Fatimah M; Huwait, Etimad A

    2017-01-01

    Borage ( Borago officinal L.) is an annual herbaceous plant of great interest because its oil contains a high percentage of γ-linolenic acid (GLA). The present work was carried out to detect fatty acids composition of the oil extracted from borage seeds (BO) and its potential effectiveness against γ-irradiation- induced hepatotoxicity in male rats. GC-MS analysis of fatty acids methyl esters of BO was performed to identify fatty acids composition. Sixty rats were divided into five groups (12 rats each): Control, irradiated; rats were exposed to (6.5 Gy) of whole body γ-radiation, BO (50 mg/kg b.wt), irradiated BO post-treated and irradiated BO prepost-treated. Six rats from each group were sacrificed at two time intervals 7 and 15 days post-irradiation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) levels, lipids profile, as well as serum and hepatic reduced glutathione (GSH) and lipid peroxide (malondialdehyde) (MDA) levels were assessed. Histopathological examination of liver sections were also carried out. The results showed that the high contents of BO extracted by cold pressing, were linoleic acid (34.23%) and GLA (24.79%). Also, oral administration of BO significantly improved serum levels of liver enzymes, lipids profile, as well as serum and hepatic GSH and MDA levels (p<0.001) as compared with irradiated rats after 15 days post irradiation. Moreover, it exerted marked amelioration against irradiation-induced histopathological changes in liver tissues. The improvement was more pronounced in irradiated BO prepost-treated group than irradiated BO post-treated. BO has a beneficial role in reducing hepatotoxicity and oxidative stress induced by radiation exposure. Therefore, BO may be used as a beneficial supplement for patients during radiotherapy treatment.

  1. A γ-Glutamyl Cyclotransferase Protects Arabidopsis Plants from Heavy Metal Toxicity by Recycling Glutamate to Maintain Glutathione Homeostasis[C][W

    PubMed Central

    Paulose, Bibin; Chhikara, Sudesh; Coomey, Joshua; Jung, Ha-il; Vatamaniuk, Olena; Dhankher, Om Parkash

    2013-01-01

    Plants detoxify toxic metals through a GSH-dependent pathway. GSH homeostasis is maintained by the γ-glutamyl cycle, which involves GSH synthesis and degradation and the recycling of component amino acids. The enzyme γ-glutamyl cyclotransferase (GGCT) is involved in Glu recycling, but the gene(s) encoding GGCT has not been identified in plants. Here, we report that an Arabidopsis thaliana protein with a cation transport regulator-like domain, hereafter referred to as GGCT2;1, functions as γ-glutamyl cyclotransferase. Heterologous expression of GGCT2;1 in Saccharomyces cerevisiae produced phenotypes that were consistent with decreased GSH content attributable to either GSH degradation or the diversion of γ-glutamyl peptides to produce 5-oxoproline (5-OP). 5-OP levels were further increased by the addition of arsenite and GSH to the medium, indicating that GGCT2;1 participates in the cellular response to arsenic (As) via GSH degradation. Recombinant GGCT2;1 converted both GSH and γ-glutamyl Ala to 5-OP in vitro. GGCT2;1 transcripts were upregulated in As-treated Arabidopsis, and ggct2;1 knockout mutants were more tolerant to As and cadmium than the wild type. Overexpression of GGCT2;1 in Arabidopsis resulted in the accumulation of 5-OP. Under As toxicity, the overexpression lines showed minimal changes in de novo Glu synthesis, while the ggct2;1 mutant increased nitrogen assimilation by severalfold, resulting in a very low As/N ratio in tissue. Thus, our results suggest that GGCT2;1 ensures sufficient GSH turnover during abiotic stress by recycling Glu. PMID:24214398

  2. Determination of some enzymes and macro- and microelements in stallion seminal plasma and their correlations to semen quality.

    PubMed

    Pesch, Sandra; Bergmann, Martin; Bostedt, Hartwig

    2006-07-15

    Seminal plasma is very important for sperm metabolism as well as sperm function and survival and transport in the female genital tract. Analysis of enzyme activities and concentrations of elements can estimate integrity and function of sperm cell membranes. In man much data are available about biochemical analyses of seminal plasma. However, not many studies have been conducted in horses yet. We collected ejaculates from 72 stallions, measured the volume, obtained seminal plasma by centrifugation and examined spermatozoa with light microscopy for motility, concentration, for dead sperm and morphology. Of seminal plasma fluid, we measured activities of aspartate-amino-transferase (AST), gamma-glutamyl-transferase (GGT), alkaline phosphatase (AlP), acid phosphatase (AcP) and lactate-dehydrogenase (LDH) as well as concentrations of sodium (Na(+)), potassium (K(+)), total and ionised calcium (Ca(TOTAL)/Ca(2+)), magnesium (Mg(2+)), phosphate (P), chloride (Cl), copper (Cu), iron (Fe) and zinc (Zn). In addition, correlations among different parameters in light microscopy and seminal plasma were statistically examined by using the Spearman rank correlation coefficient. Median enzyme activities for AST, GGT, AlP, AcP and LDH were 80.0, 7,500, 30,200, 20.0, 81.0 IU/L, respectively. Concentrations of Na(+), K(+), Ca(TOTAL), Ca(2+), Mg(2+), P, Cl were 110.5, 22.1, 2.9, 1.7, 3.1, 1.1 and 114.5 mmol/L, and of microelements Cu, Fe and Zn were 17.8, 1.9 and 13.2 micromol/L, respectively. Furthermore, we found significant correlations between semen volume as well as sperm concentration and AST, GGT, AlP, AcP and LDH as well as Fe and Zn. This made us propose a primary testicular and epididymal origin of these parameters. Significant correlation between GGT and motility may be a sign for its function for cell protection against free radicals. LDH activity significantly correlates with motility and progressive motility, live:dead-ratio and pathomorphology. In our study, LDH seems to

  3. l-Proline Accumulation and Freeze Tolerance in Saccharomyces cerevisiae Are Caused by a Mutation in the PRO1 Gene Encoding γ-Glutamyl Kinase

    PubMed Central

    Morita, Yuko; Nakamori, Shigeru; Takagi, Hiroshi

    2003-01-01

    We previously isolated a mutant which showed a high tolerance to freezing that correlated with higher levels of intracellular l-proline derived from l-proline analogue-resistant mutants. The mutation responsible for the analogue resistance and l-proline accumulation was a single nuclear dominant mutation. By introducing the mutant-derived genomic library into a non-l-proline-utilizing strain, the mutant was found to carry an allele of the wild-type PRO1 gene encoding γ-glutamyl kinase, which resulted in a single amino acid replacement; Asp (GAC) at position 154 was replaced by Asn (AAC). Interestingly, the allele of PRO1 was shown to enhance the activities of γ-glutamyl kinase and γ-glutamyl phosphate reductase, both of which catalyze the first two steps of l-proline synthesis from l-glutamate and which together may form a complex in vivo. When cultured in liquid minimal medium, yeast cells expressing the mutated γ-glutamyl kinase were found to accumulate intracellular l-proline and showed a prominent increase in cell viability after freezing at −20°C compared to the viability of cells harboring the wild-type PRO1 gene. These results suggest that the altered γ-glutamyl kinase results in stabilization of the complex or has an indirect effect on γ-glutamyl phosphate reductase activity, which leads to an increase in l-proline production in Saccharomyces cerevisiae. The approach described in this paper could be a practical method for breeding novel freeze-tolerant yeast strains. PMID:12513997

  4. Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark.

    PubMed

    Rex, Karsten Fleischer; Krarup, Henrik Bygum; Laurberg, Peter; Andersen, Stig

    2016-01-01

    Hepatitis B virus (HBV) infection is common in Arctic populations and high alcohol intake has been associated with an increased risk of a number of diseases. Yet, a description of the influence of alcohol intake in persons with HBV infection on liver biochemistry is lacking. We aimed to describe the association between reported alcohol intake and liver biochemistry taking into account also HBV infection, ethnicity, Inuit diet, body mass index (BMI), gender and age in an Arctic population. Population-based investigation of Inuit (n=441) and non-Inuit (94) in Greenland and Inuit living in Denmark (n=136). Participants filled in a questionnaire on alcohol intake and other life style factors. Blood samples were tested for aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, hepatitis B surface antigen, hepatitis B surface antibody and hepatitis B core antibody. We also performed physical examinations. Participation rate was 95% in Greenland and 52% in Denmark. An alcohol intake above the recommended level was reported by 12.9% of non-Inuit in Greenland, 9.1% of Inuit in East Greenland, 6.1% of Inuit migrants and 3.4% of Inuit in the capital of Greenland (p=0.035). Alcohol intake was associated with AST (p<0.001) and GGT (p=0.001), and HBV infection was associated with ALP (p=0.001) but not with AST, GGT, bilirubin or albumin in the adjusted analysis. Inuit had higher AST (p<0.001), GGT (p<0.001) and ALP (p=0.001) values than non-Inuit after adjustment for alcohol, diet, BMI and HBV exposure. Ethnic origin modified the association between alcohol and AST, while HBV infection did not modify the associations between alcohol and liver biochemistry. Non-Inuit in Greenland reported a higher alcohol intake than Inuit. Ethnic origin was more markedly associated with liver biochemistry than was alcohol intake, and Greenlandic ethnicity modified the effect of alcohol intake on AST. HBV infection was slightly

  5. Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark

    PubMed Central

    Rex, Karsten Fleischer; Krarup, Henrik Bygum; Laurberg, Peter; Andersen, Stig

    2016-01-01

    Background Hepatitis B virus (HBV) infection is common in Arctic populations and high alcohol intake has been associated with an increased risk of a number of diseases. Yet, a description of the influence of alcohol intake in persons with HBV infection on liver biochemistry is lacking. Objective We aimed to describe the association between reported alcohol intake and liver biochemistry taking into account also HBV infection, ethnicity, Inuit diet, body mass index (BMI), gender and age in an Arctic population. Design and methods Population-based investigation of Inuit (n=441) and non-Inuit (94) in Greenland and Inuit living in Denmark (n=136). Participants filled in a questionnaire on alcohol intake and other life style factors. Blood samples were tested for aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, hepatitis B surface antigen, hepatitis B surface antibody and hepatitis B core antibody. We also performed physical examinations. Results Participation rate was 95% in Greenland and 52% in Denmark. An alcohol intake above the recommended level was reported by 12.9% of non-Inuit in Greenland, 9.1% of Inuit in East Greenland, 6.1% of Inuit migrants and 3.4% of Inuit in the capital of Greenland (p=0.035). Alcohol intake was associated with AST (p<0.001) and GGT (p=0.001), and HBV infection was associated with ALP (p=0.001) but not with AST, GGT, bilirubin or albumin in the adjusted analysis. Inuit had higher AST (p<0.001), GGT (p<0.001) and ALP (p=0.001) values than non-Inuit after adjustment for alcohol, diet, BMI and HBV exposure. Ethnic origin modified the association between alcohol and AST, while HBV infection did not modify the associations between alcohol and liver biochemistry. Conclusions Non-Inuit in Greenland reported a higher alcohol intake than Inuit. Ethnic origin was more markedly associated with liver biochemistry than was alcohol intake, and Greenlandic ethnicity modified the effect

  6. Effect of the Aqueous Extract of Lantana grisebachii Stuck Against Bioaccumulated Arsenic-Induced Oxidative and Lipid Dysfunction in Rat Splenocytes.

    PubMed

    Ramos Elizagaray, Sabina I; Quiroga, Patricia L; Pérez, Roberto D; Sosa, Carlos; Pérez, Carlos A; Bongiovanni, Guillermina A; Soria, Elio A

    2018-06-29

    Arsenic (As) is a worldwide immunotoxic agent that is in contaminated waters and consumed by mammals. Phytotherapy may counteract its harmful effects. Lantana grisebachii Stuck (LG, Verbenaceae) and its extract are proposed as protective, given vvits in vitro bioactivity. The aim was to determine the protective capacity of the aqueous LG extract on splenocytes exposed in vivo to arsenic. Splenocytes were obtained from an arsenicosis model (Wistar rats consuming orally 0 [control; C] or 5 mg/Kg/d of As) that received 0-100 mg/Kg/d of LG extract for 30 days. As content (total reflection X-ray fluorescence), fatty acid profile (gas chromatography), γ-glutamyl transpeptidase activity (Szasz method), peroxides (xylenol orange-based assay), and nitrites (Griess reaction) were then assayed in viable splenocytes. Data were analyzed with ANOVA and the Tukey's test (p < .05). It was observed that the splenocytes contained 2.2 mg/Kg of this elemental arsenic. With γ-glutamyl transpeptidase inhibition and consequent triggering of hydroperoxides (p < .05), it was observed to increase saturated fatty acids and alter lipid profiles. LG treatment avoided damaging effects with values similar to unexposed C (p < .05), and cellular arsenic concentration (p < .0001). In conclusion, the aqueous extract of L. grisebachii counteracted arsenic toxicity in rat splenocytes by preventing its cellular accumulation and induction of lipid and redox disturbances, which may impair immune function.

  7. Non-organ-specific autoantibodies in chronic hepatitis C patients: association with histological activity and fibrosis.

    PubMed

    Chrétien, P; Chousterman, M; Abd Alsamad, I; Ozenne, V; Rosa, I; Barrault, C; Lons, T; Hagège, H

    2009-01-01

    Non-organ-specific autoantibodies (NOSAs) are frequently found in the sera of patients with Hepatitis C Virus (HCV) infection. However, no conclusive answers have been produced concerning the clinical relevance of these antibodies. To determine whether a relationship might exist between the presence of NOSA and the severity of liver disease in chronic hepatitis C. 186 treatment-naïve chronic hepatitis C patients were studied consecutively for autoantibodies. Liver biopsies were analyzed according to the Metavir score. NOSAs were present in 75 patients (40%). Anti-nuclear antibodies were found in 32% of patients (speckled pattern), anti-smooth muscle in 15% without F-actin specificity, anti-mitochondria in 0.5%, and anti-LKM1 in 0.5%, respectively. No liver-cytosol1 or soluble liver antigen antibodies were detected. There was a highly significant correlation between the positivity of NOSA and the degree of inflammation and hepatocellular injury (p = 0.001) and also with the degree of fibrosis (p < 0.0001). The presence of NOSA was associated with higher aspartate aminotransferase, gamma-glutamyl-transpeptidase, gamma-globulin and immunoglobulin G levels. By contrast, no differences were observed regarding age, gender, route of infection, duration of disease, HCV genotypes or viral load. NOSAs were associated with the most severe forms of chronic HCV infections.

  8. Association between plasma gamma-glutamyltransferase fractions and metabolic syndrome among hypertensive patients.

    PubMed

    Franzini, Maria; Scataglini, Ilenia; Ricchiuti, Angelo; Fierabracci, Vanna; Paolicchi, Aldo; Pompella, Alfonso; Dell'Omo, Giulia; Pedrinelli, Roberto; Corti, Alessandro

    2017-09-20

    Among the risk factors associated to metabolic syndrome (MetS), hypertension shows the highest prevalence in Italy. We investigated the relationship between the newly identified serum γ-glutamyltransferase (GGT) fractions, b- s- m- f-GGT, and risk factors associated to MetS in hypertensive patients. A total of ninety-five consecutive hypertensive patients were enrolled. GGT fractions were analysed by gel-filtration chromatography, and hepatic steatosis was evaluated by ultrasound. MetS was diagnosed in 36% of patients. Considering the whole group, b- and f-GGT showed the highest positive correlation with BMI, glucose, triglycerides and insulin, and the highest negative correlation with HDL cholesterol. While both serum triglycerides and insulin were independently associated with b-GGT levels, only triglycerides were independently associated with f-GGT. The values of b-GGT activity increased with steatosis grade (g0 = 1.19; g2 = 3.29; ratio g2/g0 = 2.75, p < 0.0001 linear trend). Patients with MetS showed higher levels of b-GGT, m-GGT and f-GGT [median (25 th -75 th ) U/L: 3.19 (1.50-6.59); 0.55 (0.26-0.81); 10.3 (9.1-13.6); respectively] as compared to subjects presenting with one or two MetS criteria [1.75 (0.95-2.85), p < 0.001; 0.33 (0.19-0.60), p < 0.05; 8.8 (7.0-10.6), p < 0.001]. Our data point to a potential role for b- and f-GGT fractions in identifying MetS patients among hypertensive subjects, thus providing a minimally invasive blood-based tool for MetS diagnosis.

  9. Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

    PubMed Central

    García-Samaniego, Javier; Romero, Miriam; Granados, Rafael; Alemán, Remedios; Jorge Juan, Miguel; Suárez, Dolores; Pérez, Ramón; Castellano, Gregorio; González-Portela, Carlos

    2013-01-01

    AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to peginterferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d). RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventy-eight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41

  10. A Liver Index and its Relationship to Indices of HCC Aggressiveness

    PubMed Central

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Masotto, Alberto; Trevisani, Franco

    2017-01-01

    A Hepatocellular (HCC) Aggressiveness Index was recently constructed, consisting of the sum of the scores for the 4 clinical parameters of maximum tumor size, multifocality, presence of portal vein thrombus and blood alphafetoprotein levels. It was observed that there was an association with several liver function tests. We have now formed a Liver Index from the 4 liver parameters with the highest hazard ratios with respect to HCC aggressiveness, namely: blood total bilirubin, gamma glutamyl transpeptidase (GGTP), albumin and platelet levels (cirrhosis surrogate). We found that the scores for the Liver Index related significantly to survival, but also to the Aggressiveness Index and to its individual HCC components as well as showing significant trends with the components. These results support the hypothesis that liver function is not only an important prognostic factor in HCC patients, but may also be involved in HCC biology and aggressiveness. Blood albumin, GGTP, albumin and platelet levels were used to create a Liver Index that related significantly to parameters of HCC aggressiveness. PMID:28580457

  11. Subchronic Toxicity Study in Rats of Two New Ethyl-Carbamates with Ixodicidal Activity

    PubMed Central

    Prado-Ochoa, María Guadalupe; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    Female and male Wistar rats were used to determine the subchronic oral toxicities of two new ethyl-carbamates with ixodicidal activities (ethyl-4-bromphenyl-carbamate and ethyl-4-chlorphenyl-carbamate). The evaluated carbamates were administered in the drinking water (12.5, 25 and 50 mg/kg/day) for 90 days. Exposure to the evaluated carbamates did not cause mortality or clinical signs and did not affect food consumption or weight gain. However, exposure to these carbamates produced alterations in water consumption, hematocrit, percentages of reticulocytes, plasma proteins, some biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, cholinesterase, and creatinine activities), thiobarbituric acid reactive substances, and the relative weight of the spleen. Histologically, slight pathological alterations were found in the liver that were consistent with the observed biochemical alterations. The nonobserved adverse effect levels (NOAELs) of the evaluated carbamates were 12.5 mg/kg/day for both the female and male rats. The low severity and reversibility of the majority of the observed alterations suggest that the evaluated carbamates have low subchronic toxicity. PMID:24818142

  12. Short-term space flight on nitrogenous compounds, lipoproteins, and serum proteins

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Lane, H. W.; Krauhs, J. M.

    1994-01-01

    Biochemical variables in blood were measured in venous blood samples from 38 to 72 Space Shuttle astronauts before and immediately after flights of 2 to 11 days. Mean pre- and postflight values were compared using the paired t-test or the Wilcoxon signed-rank test. The largest change in serum enzymes was a 21% increase (P = .0014) in gamma-glutamyl-transpeptidase, which may have been related to stress. The median value of apolipoprotein (apo) A-I decreased from 152 to 127 mg/dL (P < .0001), but the change in apo B (77 to 73 mg/dL) was not statistically significant, and the mean apo A-I/apo B ratio remained well above 1.5. A decrease in dietary fat and cholesterol intake during shuttle missions may have been a cause of the change in apo A-I. Twelve of the 16 nonenzyme serum proteins measured were significantly elevated (P < .05), possibly because of hemoconcentration and increased protein catabolism. The 56% increase in haptoglobin may be related to release of suppressed erythropoiesis at landing.

  13. Molecular insight on the non-covalent interactions between carbapenems and uc(l,d)-transpeptidase 2 from Mycobacterium tuberculosis: ONIOM study

    NASA Astrophysics Data System (ADS)

    Ntombela, Thandokuhle; Fakhar, Zeynab; Ibeji, Collins U.; Govender, Thavendran; Maguire, Glenn E. M.; Lamichhane, Gyanu; Kruger, Hendrik G.; Honarparvar, Bahareh

    2018-05-01

    Tuberculosis remains a dreadful disease that has claimed many human lives worldwide and elimination of the causative agent Mycobacterium tuberculosis also remains elusive. Multidrug-resistant TB is rapidly increasing worldwide; therefore, there is an urgent need for improving the current antibiotics and novel drug targets to successfully curb the TB burden. uc(l,d)-Transpeptidase 2 is an essential protein in Mtb that is responsible for virulence and growth during the chronic stage of the disease. Both uc(d,d)- and uc(l,d)-transpeptidases are inhibited concurrently to eradicate the bacterium. It was recently discovered that classic penicillins only inhibit uc(d,d)-transpeptidases, while uc(l,d)-transpeptidases are blocked by carbapenems. This has contributed to drug resistance and persistence of tuberculosis. Herein, a hybrid two-layered ONIOM (B3LYP/6-31G+(d): AMBER) model was used to extensively investigate the binding interactions of LdtMt2 complexed with four carbapenems (biapenem, imipenem, meropenem, and tebipenem) to ascertain molecular insight of the drug-enzyme complexation event. In the studied complexes, the carbapenems together with catalytic triad active site residues of LdtMt2 (His187, Ser188 and Cys205) were treated at with QM [B3LYP/6-31+G(d)], while the remaining part of the complexes were treated at MM level (AMBER force field). The resulting Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) for all complexes showed that the carbapenems exhibit reasonable binding interactions towards LdtMt2. Increasing the number of amino acid residues that form hydrogen bond interactions in the QM layer showed significant impact in binding interaction energy differences and the stabilities of the carbapenems inside the active pocket of LdtMt2. The theoretical binding free energies obtained in this study reflect the same trend of the experimental observations. The electrostatic, hydrogen bonding and Van der Waals interactions between the carbapenems and Ldt

  14. Comparison of efficacy of folic acid and silymarin in the management of antiepileptic drug induced liver injury: a randomized clinical trial.

    PubMed

    Asgarshirazi, Masoumeh; Shariat, Mamak; Sheikh, Mahdi

    2017-06-01

    Liver injury associated with antiepileptic drugs accounts for a large proportion of drug-induced liver injuries (DILI) in children. Although withdrawal of the causative agent is the only proved treatment for DILI, in some clinical situations it is not possible. Recent studies have reported promising results of using hepatoprotective drugs with antioxidant actions for the management of DILI. This study aimed to evaluate the efficacy of folic acid versus silymarin treatment in relation to decreasing liver enzymes in patients with DILI due to antiepileptic therapy. This randomized, open-label, clinical trial evaluated 55 children with epilepsy who were on antiepileptic treatment and experienced DILI. The children were randomized to receive either silymarin (5 mg/kg per day) or folic acid (1 mg per day) for one month and were followed up for three months. Liver enzymes significantly decreased in both groups. The decrease trend in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were stronger in the folic acid group compared to silymarin group (P=0.04 and P=0.007, respectively). At the end of the study patients in the folic acid group had significantly lower ALT (P=0.04), AST (P=0.02), and gamma-glutamyl transferase (GGT) (P<0.001) levels and also higher percentage of normal ALT (30.7% vs 3.4%, P=0.009) and AST (42.3% vs 0%, P<0.001), and GGT (23.1% vs 0%, P=0.008) values compared to the patients in the silymarin group. No rebound elevations in ALT, AST and GGT levels or adverse reactions were noted in neither of the study groups. Although both treatments were safe and effective in decreasing liver enzymes, folic acid seems to be superior to silymarin in the management of DILI.

  15. Prospective association of liver function biomarkers with development of hepatobiliary cancers.

    PubMed

    Stepien, Magdalena; Fedirko, Veronika; Duarte-Salles, Talita; Ferrari, Pietro; Freisling, Heinz; Trepo, Elisabeth; Trichopoulou, Antonia; Bamia, Christina; Weiderpass, Elisabete; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Racine, Antoine; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Lagiou, Pagona; Benetou, Vassiliki; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Peeters, Petra H; Lund, Eiliv; Quirós, J Ramón; Nápoles, Osmel Companioni; Sánchez, María-José; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Nystrom, Hanna; Khaw, Kay-Tee; Key, Timothy J; Gunter, Marc; Cross, Amanda; Riboli, Elio; Romieu, Isabelle; Jenab, Mazda

    2016-02-01

    Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI). In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09). This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Computational model for the acylation step of the β-lactam ring: Potential application for L,D-transpeptidase 2 in mycobacterium tuberculosis

    NASA Astrophysics Data System (ADS)

    Fakhar, Zeynab; Govender, Thavendran; Lamichhane, Gyanu; Maguire, Glenn E. M.; Kruger, Hendrik G.; Honarparvar, Bahareh

    2017-01-01

    Tuberculosis (TB) remains a major global health quandary. The peptidoglycan layer of mycobacterium tuberculosis (M.tb) consists of glycoproteins that are crosslinked by transpeptidases. Carbapenems are a subfamily of β-lactam antibiotics that inactivate the L,D-transpeptidase enzyme effectively (3 → 3 crosslinks). The mechanism of ring opening and thioester bond formation between the β-lactam core and the Cys354 active residue (for L,D-transpeptidase) during the acylation step is still the subject of considerable discussion. Herein, an acylation mechanism is proposed through four possible model transition states (TS), namely four membered-ring (TS-4, TS-4-His and TS-4-water) and six membered-ring (TS-6-water) transition states. The quantum chemical calculations for these TS models were performed with Density Functional Theory (DFT) using the B3LYP functional and the 6-31 + G(d) basis set. The calculated thermodynamic properties such as relative reaction energies (ΔEreaction), Gibbs free energies (ΔG), enthalpy energies (ΔH) and entropy contributions (ΔS) were reported at 298.15 K for the four considered pathways. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were calculated to evaluate and compare the chemical reactivities of the considered TS models. Natural bond orbital (NBO) analysis was performed to determine the effective intermolecular orbital interactions E(2) derived by the second perturbation theory. The chemical hardness (η) and softness (S) and Fukui indices (fk+, fk-) of these TS models were compared to confirm the feasibility and preference of the considered pathways. The outcome of this study will pave the way for an improved understanding of the LDT/carbapenem acylation reaction at a molecular level.

  17. Hepatoprotective Potential of Some Local Medicinal Plants against 2-Acetylaminoflourene-Induced Damage in Rat

    PubMed Central

    Adetutu, Adewale; Olorunnisola, Olubukola S.

    2013-01-01

    The in vivo micronucleus assay was used to examine the anticlastogenic effects of crude extracts of Bridelia ferruginea, Vernonia amygdalina, Tridax procumbens, Ocimum gratissimum, and Lawsonia inermis in Wistar albino rats. Extracts of doses of 100 mg/kg body weight were given to rats in five groups for seven consecutive days followed by a single dose of 2-AAF (0.5 mmol/kg body weight). The rats were sacrificed after 24 hours and their bone marrow smears were prepared on glass slides stained with Giemsa. The micronucleated polychromatic erythrocyte cells (mPCEs) were thereafter recorded. The hepatoprotective effects of the plant extracts against 2-AAF-induced liver toxicity in rats were evaluated by monitoring the levels of alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and histopathological analysis. The results of the 2-AAF-induced liver toxicity experiments showed that rats treated with the plant extracts (100 mg/kg) showed a significant decrease in mPCEs as compared with the positive control. The rats treated with the plant extracts did not show any significant change in the concentration of ALP and GGT in comparison with the negative control group whereas the 2-AAF group showed a significant increase (P < 0.05) in these parameters. Some of the leaf extracts also showed protective effects against histopathological alterations. This study suggests that the leaf extracts have hepatoprotective potential, thereby justifying their ethnopharmacological uses. PMID:24163694

  18. Hepatoprotective Potential of Some Local Medicinal Plants against 2-Acetylaminoflourene-Induced Damage in Rat.

    PubMed

    Adetutu, Adewale; Olorunnisola, Olubukola S

    2013-01-01

    The in vivo micronucleus assay was used to examine the anticlastogenic effects of crude extracts of Bridelia ferruginea, Vernonia amygdalina, Tridax procumbens, Ocimum gratissimum, and Lawsonia inermis in Wistar albino rats. Extracts of doses of 100 mg/kg body weight were given to rats in five groups for seven consecutive days followed by a single dose of 2-AAF (0.5 mmol/kg body weight). The rats were sacrificed after 24 hours and their bone marrow smears were prepared on glass slides stained with Giemsa. The micronucleated polychromatic erythrocyte cells (mPCEs) were thereafter recorded. The hepatoprotective effects of the plant extracts against 2-AAF-induced liver toxicity in rats were evaluated by monitoring the levels of alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and histopathological analysis. The results of the 2-AAF-induced liver toxicity experiments showed that rats treated with the plant extracts (100 mg/kg) showed a significant decrease in mPCEs as compared with the positive control. The rats treated with the plant extracts did not show any significant change in the concentration of ALP and GGT in comparison with the negative control group whereas the 2-AAF group showed a significant increase (P < 0.05) in these parameters. Some of the leaf extracts also showed protective effects against histopathological alterations. This study suggests that the leaf extracts have hepatoprotective potential, thereby justifying their ethnopharmacological uses.

  19. Protective effects of Nano-elemental selenium against chromium-vi-induced oxidative stress in broiler liver.

    PubMed

    Xueting, L; Rehman, M U; Zhang, H; Tian, X; Wu, X; Shixue; Mehmood, K; Zhou, D

    2018-01-01

    The valuable role of selenium in mitigation of oxidative stress and heavy metal toxicity is well-known. Thus, the aim of the current study on broiler chickens was to examine whether nano elemental selenium (Nano-Se) supplementation can reduce the effects of chromium VI (K2Cr2O7) toxicity. For this purpose, a total of 150, one-day-old broiler chickens were allotted to five groups with three replicates: control group (standard diet), poisoned group (K2Cr2O7 via drinking water), protection group (K2Cr2O7 + Nano- Se), cure group (K2Cr2O7 for initial 2 weeks and then Nano-Se), and prevention group (opposite to the cure group). The broilers were detected by the activities of marker enzymes and oxidative stress markers including, aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and superoxide dismutase (SOD), glutathione peroxidase (GSH-px), malondialdehyde (MDA), respectively. The (K2Cr2O7 administration caused histopathological damage in the liver of the chickens. Moreover, changes in serum biochemical indicators and oxidative stress parameters were also observed. Nano-Se supplementation increased the levels of GSH-px but reduced the activities of SOD, MDA, GGT, ALT and AST in the experimental groups (P less than 0.05). Our results showed that Nano-Se plays a protective role by preventing the oxidative stress induced by the chromium VI in broiler chickens.

  20. Effects of Multivitamin, Multimineral and Phytonutrient Supplementation on Nutrient Status and Biomarkers of Heart Health Risk in a Russian Population: A Randomized, Double Blind, Placebo Controlled Study

    PubMed Central

    Bogdanova, Alexandra A.; Bessonov, Vladimir V.; Sentsova, Tatiana B.; Tutelyan, Victor A.; Lin, Yumei; Kazlova, Valentina; Velliquette, Rodney A.

    2018-01-01

    The primary objective of this clinical study was to evaluate the effect of a dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood nutrient status and biomarkers of heart health risk in a Russian population. One hundred twenty healthy adults (40–70 years) were recruited for a 56-day (eight-week) randomized, double blind, placebo controlled study with parallel design. Subjects were divided into two groups and received either a VMP or a placebo (PLA) supplement. Blood nutrient levels of β-carotene, α-tocopherol, vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured at baseline and on Days 28 and 56, and quercetin was measured at baseline and on Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl transferase (GGT), uric acid and blood lipid profile, were measured at baseline and Day 56. Dietary VMP supplementation for 56 days significantly increased circulating levels of quercetin, vitamin C, RBC folate and partially prevented the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were significantly reduced (−3.97 ± 10.09 µmol/L; −1.68 ± 14.53 U/L, respectively) after VMP supplementation compared to baseline. Dietary VMP supplementation improved the nutrient status and reduced biomarkers of heart health risk in a Russian population. PMID:29370120

  1. Chemical Composition of Golden Berry Leaves Against Hepato-renal Fibrosis.

    PubMed

    Khalaf-Allah, Abd El-Rahman M; El-Gengaihi, Souad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

    2016-01-01

    The role of Physalis peruviana (golden berry) as functional food against hepato-renal fibrosis induced by carbon tetrachloride (CCl4) was evaluated. The chemical composition of leaves referred the presence of withanolides and flavonoids. Two compounds, ursolic acid and lupeol, were isolated and their structures were elucidated by different spectral analysis techniques. The biological evaluation was conducted on different animal groups; control rats, control orally treated with plant extract (500 mg/kg body weight twice a week for six consecutive weeks), CCl4 (0.5 ml/kg body weight diluted to 1:9 (v/v) in olive oil and injected intraperitoneally) group, CCl4 treated with plant extract and CCl4 treated with silymarin as a reference herbal drug. The evaluation was done through measuring oxidative stress markers; malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO). Liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea and serum protein were also evaluated. The results revealed plant safety and decrease in NO, MDA, IgG, ALP, tissue protein, bilirubin, creatinine and urea levels. Increase in SOD, AST, ALT, GGT and serum protein levels were observed. Improvement in liver and kidney histopathological architectures were also seen. In conclusion, Physalis peruviana recorded a significant protective role in liver and kidney against fibrosis. Further studies are needed to evaluate its isolated compounds and its use in pharmacological applications and clinical uses.

  2. Effects of beta-glucanase and xylanase supplementation on gastrointestinal digestive enzyme activities of weaned piglets fed a barley-based diet.

    PubMed

    Fan, C L; Han, X Y; Xu, Z R; Wang, L J; Shi, L R

    2009-04-01

    The effects of supplementing a barley-based diet for weaned piglets withexogenous beta-glucanase and xylanase on gastrointestinal digestiveenzyme activities were investigated. Thirty-six cross-bred weaned pigletswere randomly assigned to two groups with three pens based on sexand mass. Each group was fed on the diet based on barley with or withoutadded beta-glucanase and xylanase (0.15%) for a 4-week period. Theresults showed that enzyme supplementation improved growth performanceof piglets significantly (p < 0.05), but had no effect (p = 0.091)on average daily feed intake. The results also showed that supplementationof beta-glucanase and xylanase had no effect on pepsin activity in gastriccontents but slightly decreased (p = 0.092) the pepsin activity ingastric mucosa. Meanwhile, no effect of enzyme supplementation ontrypsin activity in duodenal contents was observed. However, the activitiesof amylase and lipase in duodenal contents were significantly(p < 0.05) decreased, whereas the activities of maltase, sucrase andgamma-glutamyl transpeptidase (gamma-GT) in jejunal and ileal mucosa wereenhanced significantly (p < 0.05). The improvement of disaccharidaseand gamma-GT activity may be attributed to the positive impacts of exogenousenzymes on digestion and absorption of the nutrients. In conclusion,the current results indicated that supplementation with enzymes in barley-based diets could improve the growth performance of piglets,decrease the activities of amylase and lipase in duodenal contents andincrease the activities of disaccharidase and gamma-GT in jejunal and ilealmucosa.

  3. Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione

    PubMed Central

    Kumar, Akhilesh; Tikoo, Shweta; Maity, Shuvadeep; Sengupta, Shantanu; Sengupta, Sagar; Kaur, Amandeep; Kumar Bachhawat, Anand

    2012-01-01

    ChaC1 is a mammalian proapoptic protein of unknown function induced during endoplasmic reticulum stress. We show using in vivo studies and novel in vitro assays that the ChaC family of proteins function as γ-glutamyl cyclotransferases acting specifically to degrade glutathione but not other γ-glutamyl peptides. The overexpression of these proteins (but not the catalytically dead E>Q mutants) led to glutathione depletion and enhanced apoptosis in yeast. The ChaC family is conversed across all phyla and represents a new pathway for glutathione degradation in living cells, and the first cytosolic pathway for glutathione degradation in mammalian cells. PMID:23070364

  4. Relationships between lifestyle patterns and cardio-renal-metabolic parameters in patients with type 2 diabetes mellitus: A cross-sectional study.

    PubMed

    Ogihara, Takeshi; Mita, Tomoya; Osonoi, Yusuke; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Gosho, Masahiko; Kanazawa, Akio; Watada, Hirotaka

    2017-01-01

    While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal-metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. UMIN000010932.

  5. Clinical features and risk factors of acute hepatitis E with severe jaundice

    PubMed Central

    Xu, Bin; Yu, Hai-Bin; Hui, Wei; He, Jia-Li; Wei, Lin-Lin; Wang, Zheng; Guo, Xin-Hui

    2012-01-01

    AIM: To compares the clinical features of patients infected with hepatitis E virus (HEV) with or without severe jaundice. In addition, the risk factors for HEV infection with severe jaundice were investigated. METHODS: We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group. Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum. We used χ2 analysis, Fisher’s exact test, and Student’s t test where appropriate in this study. Significant predictors in the univariate analysis were then included in a forward, stepwise multiple logistic regression model. RESULTS: No significant differences in symptoms, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or hepatitis B virus surface antigen between the two groups were observed. HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase (GGT) (median: 170.31 U/L vs 237.96 U/L, P = 0.007), significantly lower ALB levels (33.84 g/L vs 36.89 g/L, P = 0.000), significantly lower acetylcholine esterase (CHE) levels (4500.93 U/L vs 5815.28 U/L, P = 0.000) and significantly higher total bile acid (TBA) levels (275.56 μmol/L vs 147.03 μmol/L, P = 0.000) than those without severe jaundice. The median of the lowest point time tended to be lower in patients with severe jaundice (81.64% vs 96.12%, P = 0.000). HEV infected patients with severe jaundice had a significantly higher viral load (median: 134 vs 112, P = 0.025) than those without severe jaundice. HEV infected patients with severe jaundice showed a trend toward longer median hospital stay (38.17 d vs 18.36 d, P = 0.073). Multivariate logistic regression indicated that there were significant differences in age, sex, viral load, GGT, albumin, TBA, CHE

  6. Clinical features and risk factors of acute hepatitis E with severe jaundice.

    PubMed

    Xu, Bin; Yu, Hai-Bin; Hui, Wei; He, Jia-Li; Wei, Lin-Lin; Wang, Zheng; Guo, Xin-Hui

    2012-12-28

    To compares the clinical features of patients infected with hepatitis E virus (HEV) with or without severe jaundice. In addition, the risk factors for HEV infection with severe jaundice were investigated. We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group. Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum. We used χ(2) analysis, Fisher's exact test, and Student's t test where appropriate in this study. Significant predictors in the univariate analysis were then included in a forward, stepwise multiple logistic regression model. No significant differences in symptoms, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or hepatitis B virus surface antigen between the two groups were observed. HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase (GGT) (median: 170.31 U/L vs 237.96 U/L, P = 0.007), significantly lower ALB levels (33.84 g/L vs 36.89 g/L, P = 0.000), significantly lower acetylcholine esterase (CHE) levels (4500.93 U/L vs 5815.28 U/L, P = 0.000) and significantly higher total bile acid (TBA) levels (275.56 μmol/L vs 147.03 μmol/L, P = 0.000) than those without severe jaundice. The median of the lowest point time tended to be lower in patients with severe jaundice (81.64% vs 96.12%, P = 0.000). HEV infected patients with severe jaundice had a significantly higher viral load (median: 134 vs 112, P = 0.025) than those without severe jaundice. HEV infected patients with severe jaundice showed a trend toward longer median hospital stay (38.17 d vs 18.36 d, P = 0.073). Multivariate logistic regression indicated that there were significant differences in age, sex, viral load, GGT, albumin, TBA, CHE, prothrombin index, alcohol

  7. Blood profile and meat quality of Holstein-Friesian steers finished on total mixed ration or flaxseed oil-supplemented pellet mixed with reed canary grass haylage.

    PubMed

    Utama, D T; Lee, S G; Baek, K H; Chung, W S; Chung, I A; Kim, D I; Kim, G Y; Lee, S K

    2018-02-01

    Holstein-Friesian steer beef production is renowned globally as a secondary product of the milk industry. Grass feeding is a common practice in raising Holstein steers because of its low cost. Furthermore, grass feeding is an alternative way to produce beef with a balanced n-6 to n-3 fatty acids (FAs) ratio. However, the performance and meat quality of Holstein-Friesian cattle is more likely to depend on a high-quality diet. The aim of this study was to observe whether feeding two mixed diets; a corn-based total mixed ration (TMR) with winter ryegrass (Lolium perenne) or flaxseed oil-supplemented pellets with reed canary grass haylage (n-3 mix) provided benefits on carcass weight, meat quality and FA composition compared with cattle fed with reed canary grass (Phalaris arundinacea) haylage alone. In all, 15 21-month-old Holstein-Friesian steers were randomly assigned to three group pens, were allowed free access to water and were fed different experimental diets for 150 days. Blood samples were taken a week before slaughter. Carcass weight and meat quality were evaluated after slaughter. Plasma lipid levels and aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), creatine kinase (CK) and alkaline phosphatase (ALP) activities were determined. Diet did not affect plasma triglyceride levels and GGT activity. Plasma cholesterol levels, including low-density and high-density lipoproteins, were higher in both mixed-diet groups than in the haylae group. The highest activities of plasma AST, CK and ALP were observed in the haylage group, followed by n-3 mix and TMR groups, respectively. Carcass weight was lower in the haylage group than in the other groups and no differences were found between the TMR and n-3 mix groups. Although the n-3 mix-fed and haylage-fed beef provided lower n-6 to n-3 FAs ratio than TMR-fed beef, the roasted beef obtained from the TMR group was more acceptable with better overall meat physicochemical properties and sensory scores

  8. Structural control of caspase-generated glutamyl-tRNA synthetase by appended noncatalytic WHEP domains.

    PubMed

    Halawani, Dalia; Gogonea, Valentin; DiDonato, Joseph A; Pipich, Vitaliy; Yao, Peng; China, Arnab; Topbas, Celalettin; Vasu, Kommireddy; Arif, Abul; Hazen, Stanley L; Fox, Paul L

    2018-06-08

    Aminoacyl-tRNA synthetases are ubiquitous, evolutionarily conserved enzymes catalyzing the conjugation of amino acids onto cognate tRNAs. During eukaryotic evolution, tRNA synthetases have been the targets of persistent structural modifications. These modifications can be additive, as in the evolutionary acquisition of noncatalytic domains, or subtractive, as in the generation of truncated variants through regulated mechanisms such as proteolytic processing, alternative splicing, or coding region polyadenylation. A unique variant is the human glutamyl-prolyl-tRNA synthetase (EPRS) consisting of two fused synthetases joined by a linker containing three copies of the WHEP domain (termed by its presence in tryptophanyl-, histidyl-, and glutamyl-prolyl-tRNA synthetases). Here, we identify site-selective proteolysis as a mechanism that severs the linkage between the EPRS synthetases in vitro and in vivo Caspase action targeted Asp-929 in the third WHEP domain, thereby separating the two synthetases. Using a neoepitope antibody directed against the newly exposed C terminus, we demonstrate EPRS cleavage at Asp-929 in vitro and in vivo Biochemical and biophysical characterizations of the N-terminally generated EPRS proteoform containing the glutamyl-tRNA synthetase and most of the linker, including two WHEP domains, combined with structural analysis by small-angle neutron scattering, revealed a role for the WHEP domains in modulating conformations of the catalytic core and GSH- S -transferase-C-terminal-like (GST-C) domain. WHEP-driven conformational rearrangement altered GST-C domain interactions and conferred distinct oligomeric states in solution. Collectively, our results reveal long-range conformational changes imposed by the WHEP domains and illustrate how noncatalytic domains can modulate the global structure of tRNA synthetases in complex eukaryotic systems. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Lipemia interferences in routine clinical biochemical tests.

    PubMed

    Calmarza, Pilar; Cordero, José

    2011-01-01

    Lipemic specimens are a common and frequent, but yet unresolved problem in clinical chemistry, and may produce significant interferences in the analytical results of different biochemical parameters. The aim of this study was to examine the effect of lipid removal using ultracentrifugation of lipemic samples, on some routine biochemistry parameters. Among all the samples obtained daily in our laboratory, the ones which were visibly muddy were selected and underwent to a process of ultracentrifugation, being determined a variety of biochemical tests before and after ultracentrifugation. A total of 110 samples were studied. We found significant differences in all the parameters studied except for total bilirubin, glucose, gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST). The greatest differences in the parameters analyzed were found in the concentration of alanine aminotransferase (ALT) (7.36%) and the smallest ones in the concentration of glucose (0.014%). Clinically significant interferences were found for phosphorus, creatinine, total protein and calcium. Lipemia causes clinically significant interferences for phosphorus, creatinine, total protein and calcium measurement and those interferences could be effectively removed by ultracentrifugation.

  10. Golden berry juice attenuates the severity of hepatorenal injury.

    PubMed

    El-Gengaihi, Souad E; Hamed, Manal A; Khalaf-Allah, Abd El-Rahman M; Mohammed, Mona A

    2013-12-01

    The aim of the present work is to investigate the potential of Physalis peruviana fruits as a hepatorenal protective agent against carbon tetrachloride (CCl4)-induced hepatic and renal fibrosis. The phytochemical screening test revealed the presence of alkaloids, free withanolides, glycowithanolides, and flavonoids. Acute toxicity study (500, 1000, and 1500 mg/kg body weight) revealed extract safety. The biological evaluation was conducted on different animal groups: control, control treated with fruit, CCl4 group, CCl4 treated with fruit, and CCl4 treated with silymarin drug. The evaluation was done through measuring oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO). Liver function indices such as aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, and total protein were estimated. Kidney disorder biomarkers such as creatinine, urea, and serum protein were also evaluated. Treatment improved all the investigated parameters, and the histopathological analysis confirmed our results. In conclusion, Physalis peruviana fruit succeeded to protect liver and kidney against fibrosis. Further studies are needed to identify the molecules responsible for its pharmacological application.

  11. Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study.

    PubMed

    Monami, Matteo; Bardini, Gianluca; Lamanna, Caterina; Pala, Laura; Cresci, Barbara; Francesconi, Paolo; Buiatti, Eva; Rotella, Carlo M; Mannucci, Edoardo

    2008-03-01

    The aim of the study was to assess gamma-glutamyl transpeptidase (gamma-GT), alanine aminotransferase, and aspartate aminotransferase (AST) in the prediction of diabetes and cardiovascular disease (CVD) in subjects free from hepatic diseases other than nonalcoholic fatty liver disease. The present analysis was performed on the cohort of subjects enrolled in the Firenze Bagno a Ripoli (FIBAR) study, a screening program for diabetes performed between 1 March 2001 and 31 December 2003 in the city of Florence on 3124 subjects who underwent an oral glucose tolerance test. Incident cases of diabetes in nondiabetic subjects (n = 2662) were obtained through databases of drug prescriptions, hospital admissions, and lists of subjects eligible for reimbursement. Incident CVD in subjects free of diabetes and CVD at enrollment (n = 2617) was identified through hospital admissions and through the register of causes of death. Mean follow-up was 39.6 +/- 12.0 months and 39.8 +/- 11.4 months for diabetes and CVD, respectively. Yearly incidence of diabetes and CVD was 0.4% and 0.2%, respectively. After adjustment for age and sex, gamma-GT >40 U/L was associated with increased incidence of diabetes and CVD (hazard ratio [95% confidence interval]: 2.54 [1.26-5.11], P < .05 and 2.21 [0.98-5.43], P < .10, respectively). Risk of diabetes, but not of CVD, was increased in patients with gamma-GT in the 25- to 40-U/L range. After adjustment for confounders, AST >40 U/L predicted CVD (hazard ratio, 6.5 [95% confidence interval, 1.5-28.1]), but not diabetes. Elevated gamma-GT or AST is an independent predictor of CVD. An increase of gamma-GT levels above the reference range, or also in the upper reference range, is an independent predictor of incident diabetes.

  12. Crystal structures of the transpeptidase domain of the Mycobacterium tuberculosis penicillin-binding protein PonA1 reveal potential mechanisms of antibiotic resistance.

    PubMed

    Filippova, Ekaterina V; Kieser, Karen J; Luan, Chi-Hao; Wawrzak, Zdzislaw; Kiryukhina, Olga; Rubin, Eric J; Anderson, Wayne F

    2016-06-01

    Mycobacterium tuberculosis is a human respiratory pathogen that causes the deadly disease tuberculosis. The rapid global spread of antibiotic-resistant M. tuberculosis makes tuberculosis infections difficult to treat. To overcome this problem new effective antimicrobial strategies are urgently needed. One promising target for new therapeutic approaches is PonA1, a class A penicillin-binding protein, which is required for maintaining physiological cell wall synthesis and cell shape during growth in mycobacteria. Here, crystal structures of the transpeptidase domain, the enzymatic domain responsible for penicillin binding, of PonA1 from M. tuberculosis in the inhibitor-free form and in complex with penicillin V are reported. We used site-directed mutagenesis, antibiotic profiling experiments, and fluorescence thermal shift assays to measure PonA1's sensitivity to different classes of β-lactams. Structural comparison of the PonA1 apo-form and the antibiotic-bound form shows that binding of penicillin V induces conformational changes in the position of the loop β4'-α3 surrounding the penicillin-binding site. We have also found that binding of different antibiotics including penicillin V positively impacts protein stability, while other tested β-lactams such as clavulanate or meropenem resulted in destabilization of PonA1. Our antibiotic profiling experiments indicate that the transpeptidase activity of PonA1 in both M. tuberculosis and M. smegmatis mediates tolerance to specific cell wall-targeting antibiotics, particularly to penicillin V and meropenem. Because M. tuberculosis is an important human pathogen, these structural data provide a template to design novel transpeptidase inhibitors to treat tuberculosis infections. Structural data are available in the PDB database under the accession numbers 5CRF and 5CXW. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  13. Sortase Transpeptidases: Structural Biology and Catalytic Mechanism

    PubMed Central

    Jacobitz, Alex W.; Kattke, Michele D.; Wereszczynski, Jeff; Clubb, Robert T.

    2017-01-01

    Gram-positive bacteria use sortase cysteine transpeptidase enzymes to covalently attach proteins to their cell wall and to assemble pili. In pathogenic bacteria sortases are potential drug targets, as many of the proteins that they display on the microbial surface play key roles in the infection process. Moreover, the Staphylococcus aureus Sortase A (SaSrtA) enzyme has been developed into a valuable biochemical reagent because of its ability to ligate biomolecules together in vitro via a covalent peptide bond. Here we review what is known about the structures and catalytic mechanism of sortase enzymes. Based on their primary sequences, most sortase homologs can be classified into six distinct subfamilies, called class A–F enzymes. Atomic structures reveal unique, class-specific variations that support alternate substrate specificities, while structures of sortase enzymes bound to sorting signal mimics shed light onto the molecular basis of substrate recognition. The results of computational studies are reviewed that provide insight into how key reaction intermediates are stabilized during catalysis, as well as the mechanism and dynamics of substrate recognition. Lastly, the reported in vitro activities of sortases are compared, revealing that the transpeptidation activity of SaSrtA is at least 20-fold faster than other sortases that have thus far been characterized. Together, the results of the structural, computational, and biochemical studies discussed in this review begin to reveal how sortases decorate the microbial surface with proteins and pili, and may facilitate ongoing efforts to discover therapeutically useful small molecule inhibitors. PMID:28683919

  14. Haematinic Deficiency and Macrocytosis in Middle-Aged and Older Adults

    PubMed Central

    Harrington, Janas; Cadogan, Sharon; Honari, Bahman; Perera, Kanthi; Fitzgerald, Anthony P.; Perry, Ivan J.; Cahill, Mary R.

    2013-01-01

    Objective To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults. Methods A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT). Results The overall prevalence (95% C.I.) of anaemia (Hb <13.5g/dl men and 11.3 g/dl women) was 4.6% (2.9%–6.4%) in men and 1.0% (0.2%–1.9%) in women. Iron deficiency (ferritin <17ng/ml men and <11ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3ng/ml) and serum B12 (<120ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%). Conclusions Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland

  15. Electron microscopic, genetic and protein expression analyses of Helicobacter acinonychis strains from a Bengal tiger.

    PubMed

    Tegtmeyer, Nicole; Rivas Traverso, Francisco; Rohde, Manfred; Oyarzabal, Omar A; Lehn, Norbert; Schneider-Brachert, Wulf; Ferrero, Richard L; Fox, James G; Berg, Douglas E; Backert, Steffen

    2013-01-01

    Colonization by Helicobacter species is commonly noted in many mammals. These infections often remain unrecognized, but can cause severe health complications or more subtle host immune perturbations. The aim of this study was to isolate and characterize putative novel Helicobacter spp. from Bengal tigers in Thailand. Morphological investigation (Gram-staining and electron microscopy) and genetic studies (16SrRNA, 23SrRNA, flagellin, urease and prophage gene analyses, RAPD DNA fingerprinting and restriction fragment polymorphisms) as well as Western blotting were used to characterize the isolated Helicobacters. Electron microscopy revealed spiral-shaped bacteria, which varied in length (2.5-6 µm) and contained up to four monopolar sheathed flagella. The 16SrRNA, 23SrRNA, sequencing and protein expression analyses identified novel H. acinonychis isolates closely related to H. pylori. These Asian isolates are genetically very similar to H. acinonychis strains of other big cats (cheetahs, lions, lion-tiger hybrid and other tigers) from North America and Europe, which is remarkable in the context of the great genetic diversity among worldwide H. pylori strains. We also found by immunoblotting that the Bengal tiger isolates express UreaseA/B, flagellin, BabA adhesin, neutrophil-activating protein NapA, HtrA protease, γ-glutamyl-transpeptidase GGT, Slt lytic transglycosylase and two DNA transfer relaxase orthologs that were known from H. pylori, but not the cag pathogenicity island, nor CagA, VacA, SabA, DupA or OipA proteins. These results give fresh insights into H. acinonychis genetics and the expression of potential pathogenicity-associated factors and their possible pathophysiological relevance in related gastric infections.

  16. Electron Microscopic, Genetic and Protein Expression Analyses of Helicobacter acinonychis Strains from a Bengal Tiger

    PubMed Central

    Tegtmeyer, Nicole; Rivas Traverso, Francisco; Rohde, Manfred; Oyarzabal, Omar A.; Lehn, Norbert; Schneider-Brachert, Wulf; Ferrero, Richard L.; Fox, James G.; Berg, Douglas E.; Backert, Steffen

    2013-01-01

    Colonization by Helicobacter species is commonly noted in many mammals. These infections often remain unrecognized, but can cause severe health complications or more subtle host immune perturbations. The aim of this study was to isolate and characterize putative novel Helicobacter spp. from Bengal tigers in Thailand. Morphological investigation (Gram-staining and electron microscopy) and genetic studies (16SrRNA, 23SrRNA, flagellin, urease and prophage gene analyses, RAPD DNA fingerprinting and restriction fragment polymorphisms) as well as Western blotting were used to characterize the isolated Helicobacters. Electron microscopy revealed spiral-shaped bacteria, which varied in length (2.5–6 µm) and contained up to four monopolar sheathed flagella. The 16SrRNA, 23SrRNA, sequencing and protein expression analyses identified novel H. acinonychis isolates closely related to H. pylori. These Asian isolates are genetically very similar to H. acinonychis strains of other big cats (cheetahs, lions, lion-tiger hybrid and other tigers) from North America and Europe, which is remarkable in the context of the great genetic diversity among worldwide H. pylori strains. We also found by immunoblotting that the Bengal tiger isolates express UreaseA/B, flagellin, BabA adhesin, neutrophil-activating protein NapA, HtrA protease, γ-glutamyl-transpeptidase GGT, Slt lytic transglycosylase and two DNA transfer relaxase orthologs that were known from H. pylori, but not the cag pathogenicity island, nor CagA, VacA, SabA, DupA or OipA proteins. These results give fresh insights into H. acinonychis genetics and the expression of potential pathogenicity-associated factors and their possible pathophysiological relevance in related gastric infections. PMID:23940723

  17. Study of new ways of supplementary and combinatory therapy of rheumatoid arthritis with immunomodulators. Glucomannan and Imunoglukán in adjuvant arthritis.

    PubMed

    Bauerová, K; Paulovicová, E; Mihalová, D; Svík, K; Ponist, S

    2009-01-01

    We studied the anti-arthritic activity of glucomannan (GM) isolated from Candida utilis and of Imunoglukán, a beta-(1,3/1,6)-D-glucan (IMG) isolated from Pleurotus ostreatus. Adjuvant arthritis (AA) was induced intradermally by the injection of Mycobacterium butyricum in incomplete Freund's adjuvant to Lewis rats. Blood for biochemical and immunological analysis was collected on experimental days 1, 14, 21, and 28. A clinical parameter--hind paw volume (HPV)--was also measured. The detection of IL-1 alpha, IL-4, TNF alpha, and MCP-1 was done by immunoflowcytometry. On day 28--the end of the experiment--we determined spectrophotometrically: the total anti-oxidant status (TAS) of plasma samples along with thiobarbituric acid-reacting substances (TBARS) levels in plasma and we assessed the activity of gamma-glutamyl transferase (GGT) in hind paw joint homogenate. The experiments included healthy animals, arthritic animals without treatment, and arthritic animals with administration of glucomannan (GM-AA) in the oral daily dose of 15 mg/kg b.w. and of IMG (IMG-AA) in the oral daily dose of 2 mg/kg b.w. The progress of AA was manifested by all parameters monitored. Both substances had beneficial effects on HPV, TBARS levels, GGT activity, and TAS levels. For cytokine assessment, only IMG-AA samples were selected, considering the significant HPV improvement accompanied with the observed anti-oxidant action. IMG administration had a positive immunomodulating effect on all cytokine plasma levels measured, changed markedly due to arthritis progression. Thus, IMG may be considered as a candidate for combinatorial therapy of rheumatoid arthritis.

  18. Effects of creatine supplementation on biomarkers of hepatic and renal function in young trained rats.

    PubMed

    Souza, William Marciel; Heck, Thiago Gomes; Wronski, Evanio Castor; Ulbrich, Anderson Zampier; Boff, Everton

    2013-11-01

    Creatine supplementation has been widely used by athletes and young physical exercise practioneers in order of increasing muscle mass and enhancing athletic performance, but their use/overuse may represent a health risk on hepatic and renal impaired function. In this study, we evaluated the effects of 40 days of oral creatine supplementation on hepatic and renal function biomarkers in a young animal model. Wistar rats (5 weeks old) were divided in five groups (n = 7): control (CONTR), oral creatine supplementation (CREAT), moderate exercise training (EXERC), moderate exercise training plus oral creatine supplementation (EXERC + CREAT) and pathological group (positive control for liver and kidney injury) by the administration of rifampicin (RIFAMPICIN). Exercise groups were submitted to 60 min/day of swimming exercise session with a 4% of body weight workload for six weeks. The EXERC + CREAT showed the higher body weight at the end of the training protocol. The CREAT and EXERC + CREAT group showed an increase in hepatic (Aspartate transaminase and gamma-glutamyl transpeptidase) and renal (urea and creatinine) biomarkers levels (p < 0.05). Our study showed that the oral creatine supplementation promoted hepatic and renal function challenge in young rats submitted to moderate exercise training.

  19. Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in D-galactosamine-induced hepatotoxic rats.

    PubMed

    Pushpavalli, Ganesan; Veeramani, Chinnadurai; Pugalendi, Kodukkur Viswanathan

    2008-01-01

    D-galactosamine is a well-established hepatotoxicant that induces a diffuse type of liver injury closely resembling human viral hepatitis. D-galactosamine by its property of generating free radicals causes severe damage to the membrane and affects almost all organs of the human body. The leaves of Piper betle L., a commonly used masticatory in Asian countries, possess several biological properties. Our aim is to investigate the in vivo antioxidant potential of P. betle leaf-extract against oxidative stress induced by D-galactosamine intoxication in male albino Wistar rats. Toxicity was induced by an intraperitoneal injection of D-galactosamine, 400 mg/kg body weight (BW) for 21 days. Rats were treated with P. betle extract (200 mg/kg BW) via intragastric intubations. We assessed the activities of liver marker enzymes (aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase) and levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione. The extract significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, and liver marker enzymes when compared with the D-galactosamine treated group, demonstrating its hepatoprotective and antioxidant properties.

  20. Efficacy of Essential Oils of Thymus vulgaris and Origanum vulgare on Echinococcus granulosus

    PubMed Central

    Pensel, P. E.; Maggiore, M. A.; Gende, L. B.; Eguaras, M. J.; Denegri, M. G.; Elissondo, M. C.

    2014-01-01

    The aim of the present work was to determine the in vitro effect of T. vulgaris and O. vulgare essential oils against E. granulosus protoscoleces and cysts. Essential oils were added to the medium resulting in thymol final concentrations of 10 μg/mL. The essential oils had a time-dependent effect provoking the complete loss of protoscolex viability after 72 days of postincubation. The results were confirmed at the ultrastructure level. Loss of infectivity in protoscoleces incubated with O. vulgare after 60 days was observed. On the other hand, the weight of cysts recorded in mice inoculated with T. vulgaris treated protoscoleces was significantly lower than that obtained in control group. Gamma-glutamyl-transpeptidase activity was readily detected in the culture supernatant of protoscoleces treated either with the essential oils or thymol. T. vulgaris and O. vulgare essential oils and thymol can induce cell apoptosis of protoscoleces after short incubation times. The efficacy of T. vulgaris and O. vulgare essential oils was also demonstrated in vitro on E. granulosus murine cysts. Our data suggest that essential oils of T. vulgaris and O. vulgare have anthelmintic effect against protoscoleces and cysts of E. granulosus. PMID:25180033

  1. Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats.

    PubMed

    Jayakumar, Subramaniyan; Madankumar, Arumugam; Asokkumar, Selvamani; Raghunandhakumar, Subramanian; Gokula dhas, Krishnan; Kamaraj, Sattu; Divya, Michael Georget Josephine; Devaki, Thiruvengadam

    2012-01-01

    Antioxidants are one of the key players in tumorigenesis, several natural and synthetic antioxidants were shown to have anticancer effects. The aim of the present study is to divulge the chemopreventive nature of carvacrol during diethylnitrosamine (DEN)-induced liver cancer in male wistar albino rats. Administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (γGT). The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR). Carvacrol supplementation (15 mg/kg body weight) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer. Histological observations and transmission electron microscopy studies were also carried out, which added supports to the chemopreventive action of the carvacrol against DEN-induction during liver cancer progression. These findings suggest that carvacrol prevents lipid peroxidation, hepatic cell damage, and protects the antioxidant system in DEN-induced hepatocellular carcinogenesis.

  2. Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting β-Lactam Resistance Levels in Streptococcus pneumoniae

    PubMed Central

    Metcalf, Benjamin J.; Chochua, Sopio; Li, Zhongya; Gertz, Robert E.; Walker, Hollis; Hawkins, Paulina A.; Tran, Theresa; Whitney, Cynthia G.; McGee, Lesley; Beall, Bernard W.

    2016-01-01

    ABSTRACT β-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of β-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking β-lactam resistance could benefit disease surveillance. Here we developed a classification system in which a pneumococcal isolate is assigned to a “PBP type” based on sequence signatures in the transpeptidase domains (TPDs) of the three critical penicillin-binding proteins (PBPs), PBP1a, PBP2b, and PBP2x. We identified 307 unique PBP types from 2,528 invasive pneumococcal isolates, which had known MICs to six β-lactams based on broth microdilution. We found that increased β-lactam MICs strongly correlated with PBP types containing divergent TPD sequences. The PBP type explained 94 to 99% of variation in MICs both before and after accounting for genomic backgrounds defined by multilocus sequence typing, indicating that genomic backgrounds made little independent contribution to β-lactam MICs at the population level. We further developed and evaluated predictive models of MICs based on PBP type. Compared to microdilution MICs, MICs predicted by PBP type showed essential agreement (MICs agree within 1 dilution) of >98%, category agreement (interpretive results agree) of >94%, a major discrepancy (sensitive isolate predicted as resistant) rate of <3%, and a very major discrepancy (resistant isolate predicted as sensitive) rate of <2% for all six β-lactams. Thus, the PBP transpeptidase signatures are robust indicators of MICs to different β-lactam antibiotics in clinical pneumococcal isolates and serve as an accurate alternative to phenotypic susceptibility testing. PMID:27302760

  3. Relationships between lifestyle patterns and cardio-renal-metabolic parameters in patients with type 2 diabetes mellitus: A cross-sectional study

    PubMed Central

    Ogihara, Takeshi; Osonoi, Yusuke; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Gosho, Masahiko; Kanazawa, Akio; Watada, Hirotaka

    2017-01-01

    Introduction While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal—metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. Participants and methods The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Results Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. Conclusions The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. Trial registration UMIN000010932 PMID:28273173

  4. Qualification of the GASGUARD® SAS GGT Arsine Sub-Atmospheric Gas Delivery System for Ion Implantation

    NASA Astrophysics Data System (ADS)

    Dunn, James P.; Rolland, James L.; Grim, James S.; Machado, Reinaldo M.; Hartz, Christopher L.

    2006-11-01

    A beta level evaluation of the GASGUARD® SAS GGT Arsine ion implant dopant supply developed by Air Products and Chemicals, Inc. was conducted by Atmel Corporation. The evaluation included characterization of the normalized wafer yield, mass spectra, ionization efficiency, flow rate, beam current, extraction of usable material and cylinder lifetime. This new and novel sub-atmospheric dopant gas delivery system utilizes a unique electrochemical process, which can generate, on demand, high flows of arsine at a constant 400 torr pressure while limiting net inventory of arsine to only 1 gram. This paper illustrates how Atmel Corporation evaluated and released this new arsine dopant delivery system for commercial production and verified high delivery capacity, resulting in reduced gas costs and increased cylinder life compared to the traditional adsorbent based technology.

  5. Glutathione Synthetase Deficiency, an Inborn Error of Metabolism Involving the γ-Glutamyl Cycle in Patients with 5-Oxoprolinuria (Pyroglutamic Aciduria)

    PubMed Central

    Wellner, Vaira P.; Sekura, Ronald; Meister, Alton; Larsson, Agne

    1974-01-01

    Enzyme studies on placenta, cultured skin fibroblasts, and erythrocytes from two sisters with the inborn error 5-oxoprolinuria (pyroglutamic aciduria) indicate that the metabolic lesion in this disease is at the glutathione synthetase (EC 6.3.2.3) step of the γ-glutamyl cycle. Excessive urinary excretion of 5-oxoproline by these patients appears to be associated with increased synthesis of γ-glutamyl-cysteine and formation of 5-oxoproline from this dipeptide. Thus, 5-oxoproline is produced in amounts that exceed the normal capacity of 5-oxoprolinase to convert it to glutamate. The data indicate that it may be possible to identify individuals who are heterozygous for this trait by determinations of erythrocyte glutathione synthetase. PMID:4152248

  6. Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

    PubMed

    Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R; Partovi, Nilufar; Yoshida, Eric M

    2016-09-28

    Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited

  7. Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review

    PubMed Central

    Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R.; Partovi, Nilufar; Yoshida, Eric M.

    2016-01-01

    Abstract Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids

  8. Is carbon dioxide a safe and good alternative for diatrizoate meglumine as a contrast in digital subtraction angiography?

    PubMed

    Hegde, U N; Khanapet, M S; Rajapurkar, M M; Gang, S D; Gohel, K D; Rane, G; Parikh, P; Patil, D; Desai, T; Patil, P; Kelawala, N

    2009-01-01

    Contrast-induced nephropathy is well-known sequelae of iodinated contrast (diatrizoate meglumine). Carbon dioxide (CO(2)) can be used as an alternative contrast agent. The aim of this study was to compare the renal injury and the quality of images of aortogram using iodinated contrast versus CO(2) using digital subtraction angiography (DSA). This prospective randomized study was done in 29 healthy dogs using DSA aortogram. Dogs were randomly assigned to receive iodinated contrast or CO(2). 6-F pigtail catheter was introduced via femoral artery approach to perform aortogram under general anesthesia. Serum creatinine (S.Cr.) and urinary enzymes, namely: N-acetyl D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and gamma glutamyl transferase (GGT), were measured before and 48 hours after aortogram. There was no change in S.Cr. in both the groups. Significantly more enzymuria was seen following iodinated contrast than CO(2). Enzymuria pre and postaortogram following the iodinated contrast was GGT: 14.9 +/- 5.92 vs. 26.2 +/- 15.1 (P = 0.001), NAG: 1.63 +/- 0.90 vs. 3.6 +/- 2.14 (P = 0.0001), and AAP: 1.51 +/- 0.75 vs. 3.38 2.41 (P = 0.001), and in the CO(2) group was GGT: 15.5 +/- 4.9 vs. 21.1 +/- 9.04 (P = 0.02), NAG: 2.12 +/- 1.06 vs. 3.82 3.27 (P = 0.08), and AAP: 1.28 +/- 0.76 vs. 2.51 +/- 1.72 (P = 0.03). More than 50% increase over the preprocedural value was significantly less following CO(2). Images obtained with iodinated contrast were superior to those with CO(2,) however, the quality of image with CO(2) was adequate for delineation of the renal artery and major branches. Both iodinated contrast and CO(2) cause significant enzymuria. More severe enzymuria (>50% increase) was seen significantly less with the use of CO(2). Quality of images is better with iodinated contrast.

  9. Is carbon dioxide a safe and good alternative for diatrizoate meglumine as a contrast in digital subtraction angiography?

    PubMed Central

    Hegde, U. N.; Khanapet, M. S.; Rajapurkar, M. M.; Gang, S. D.; Gohel, K. D.; Rane, G.; Parikh, P.; Patil, D.; Desai, T.; Patil, P.; Kelawala, N.

    2009-01-01

    Contrast-induced nephropathy is well-known sequelae of iodinated contrast (diatrizoate meglumine). Carbon dioxide (CO2) can be used as an alternative contrast agent. The aim of this study was to compare the renal injury and the quality of images of aortogram using iodinated contrast versus CO2 using digital subtraction angiography (DSA). This prospective randomized study was done in 29 healthy dogs using DSA aortogram. Dogs were randomly assigned to receive iodinated contrast or CO2. 6-F pigtail catheter was introduced via femoral artery approach to perform aortogram under general anesthesia. Serum creatinine (S.Cr.) and urinary enzymes, namely: N-acetyl D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and gamma glutamyl transferase (GGT), were measured before and 48 hours after aortogram. There was no change in S.Cr. in both the groups. Significantly more enzymuria was seen following iodinated contrast than CO2. Enzymuria pre and postaortogram following the iodinated contrast was GGT: 14.9 ± 5.92 vs. 26.2 ± 15.1 (P = 0.001), NAG: 1.63 ± 0.90 vs. 3.6 ± 2.14 (P = 0.0001), and AAP: 1.51 ± 0.75 vs. 3.38 2.41 (P = 0.001), and in the CO2 group was GGT: 15.5 ± 4.9 vs. 21.1 ± 9.04 (P = 0.02), NAG: 2.12 ± 1.06 vs. 3.82 3.27 (P = 0.08), and AAP: 1.28 ± 0.76 vs. 2.51 ± 1.72 (P = 0.03). More than 50% increase over the preprocedural value was significantly less following CO2. Images obtained with iodinated contrast were superior to those with CO2, however, the quality of image with CO2 was adequate for delineation of the renal artery and major branches. Both iodinated contrast and CO2 cause significant enzymuria. More severe enzymuria (>50% increase) was seen significantly less with the use of CO2. Quality of images is better with iodinated contrast. PMID:20352006

  10. Standardization of gamma-glutamyltransferase assays by intermethod calibration. Effect on determining common reference limits.

    PubMed

    Steinmetz, Josiane; Schiele, Françoise; Gueguen, René; Férard, Georges; Henny, Joseph

    2007-01-01

    The improvement of the consistency of gamma-glutamyltransferase (GGT) activity results among different assays after calibration with a common material was estimated. We evaluated if this harmonization could lead to reference limits common to different routine methods. Seven laboratories measured GGT activity using their own routine analytical system both according to the manufacturer's recommendation and after calibration with a multi-enzyme calibrator [value assigned by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference procedure]. All samples were re-measured using the IFCC reference procedure. Two groups of subjects were selected in each laboratory: a group of healthy men aged 18-25 years without long-term medication and with alcohol consumption less than 44 g/day and a group of subjects with elevated GGT activity. The day-to-day coefficients of variation were less than 2.9% in each laboratory. The means obtained in the group of healthy subjects without common calibration (range of the means 16-23 U/L) were significantly different from those obtained by the IFCC procedure in five laboratories. After calibration, the means remained significantly different from the IFCC procedure results in only one laboratory. For three calibrated methods, the slope values of linear regression vs. the IFCC procedure were not different from the value 1. The results obtained with these three methods for healthy subjects (n=117) were gathered and reference limits were calculated. These were 11-49 U/L (2.5th-97.5th percentiles). The calibration also improved the consistency of elevated results when compared to the IFCC procedure. The common calibration improved the level of consistency between different routine methods. It permitted to define common reference limits which are quite similar to those proposed by the IFCC. This approach should lead to a real benefit in terms of prevention, screening, diagnosis, therapeutic monitoring and for

  11. Identification and Characterization of γ-Glutamylamine Cyclotransferase, an Enzyme Responsible for γ-Glutamyl-ϵ-lysine Catabolism*

    PubMed Central

    Oakley, Aaron J.; Coggan, Marjorie; Board, Philip G.

    2010-01-01

    γ-Glutamylamine cyclotransferase (GGACT) is an enzyme that converts γ-glutamylamines to free amines and 5-oxoproline. GGACT shows high activity toward γ-glutamyl-ϵ-lysine, derived from the breakdown of fibrin and other proteins cross-linked by transglutaminases. The enzyme adopts the newly identified cyclotransferase fold, observed in γ-glutamylcyclotransferase (GGCT), an enzyme with activity toward γ-glutamyl-α-amino acids (Oakley, A. J., Yamada, T., Liu, D., Coggan, M., Clark, A. G., and Board, P. G. (2008) J. Biol. Chem. 283, 22031–22042). Despite the absence of significant sequence identity, several residues are conserved in the active sites of GGCT and GGACT, including a putative catalytic acid/base residue (GGACT Glu82). The structure of GGACT in complex with the reaction product 5-oxoproline provides evidence for a common catalytic mechanism in both enzymes. The proposed mechanism, combined with the three-dimensional structures, also explains the different substrate specificities of these enzymes. Despite significant sequence divergence, there are at least three subfamilies in prokaryotes and eukaryotes that have conserved the GGCT fold and GGCT enzymatic activity. PMID:20110353

  12. Accumulation of 5-Oxoproline in Mouse Tissues After Inhibition of 5-Oxoprolinase and Administration of Amino Acids: Evidence for Function of the γ-Glutamyl Cycle*

    PubMed Central

    Van Der Werf, Paul; Stephani, Ralph A.; Meister, Alton

    1974-01-01

    5-Oxoprolinase catalyzes the conversion of 5-oxo-L-proline (L-pyroglutamate, L-2-pyrrolidone-5-carboxylate) to L-glutamate with concomitant stoichiometric cleavage of ATP to ADP and inorganic orthophosphate. In this reaction, a step in the γ-glutamyl cycle, 5-oxoproline (formed by the action of γ-glutamylcyclotransferase on γ-glutamyl amino acids, which are in turn formed by transpeptidation of amino acids with glutathione), is made available for glutathione synthesis. When mice are injected with L-2-imidazolidone-4-carboxylate, a competitive inhibitor of 5-oxoprolinase, they accumulate 5-oxoproline in their tissues (kidney, liver, brain, and eye) and excrete it in the urine. Mice given the inhibitor together with one of several L-amino acids accumulate and excrete much more 5-oxoproline than when they are given the inhibitor alone. Such augmentation of 5-oxoproline accumulation offers evidence for the function of the γ-glutamyl cycle in vivo and supports the view that 5-oxoproline is a quantitatively significant metabolite. Images PMID:4151516

  13. Effect of tributyltin on testicular development in Sebastiscus marmoratus and the mechanism involved.

    PubMed

    Zhang, Jiliang; Zuo, Zhenghong; He, Chengyong; Cai, Jiali; Wang, Yuqing; Chen, Yixin; Wang, Chonggang

    2009-07-01

    Organotin compounds, such as tributyltin (TBT), that have been used as antifouling biocides can induce masculinization in female mollusks. However, few studies addressing the effects of TBT on fishes have been reported. The present study was conducted to investigate the effects of TBT at environmentally relevant concentrations (1, 10, and 100 ng/L) on testicular development in Sebastiscus marmoratus and to gain insight into its mechanism of action. After exposure for 48 d, the gonadosomatic index had decreased in a dose-dependent manner. Although the testosterone levels in the testes were elevated and the 17beta-estradiol levels were decreased, spermatogenesis was suppressed. Moreover, gamma-glutamyl transpeptidase activity (which is used as a Sertoli cell marker) was decreased in a dose-dependent manner after TBT exposure, and serious interstitial fibrosis was observed in the interlobular septa of the testes in the 100 ng/L TBT test group. Increases in the retinoid X receptors and peroxisome proliferator activated receptor gamma expression and the progressive enlargement of lipid droplets in the testes were observed after TBT exposure. Estrogen receptor alpha levels in the testes of the fish exposed to TBT decreased in a dose-dependent manner. The reduction of estrogen receptor alpha mRNA resulted from the decrease of 17beta-estradiol levels, and the progressive enlargement of lipid droplets may have contributed to the dysfunction of the Sertoli cells, which then disrupted spermatogenesis.

  14. Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients.

    PubMed

    Askari, Faezeh; Rashidkhani, Bahram; Hekmatdoost, Azita

    2014-02-01

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of hepatic injury in the world. One of the most important therapeutic strategies for this disease is modulating insulin resistance and oxidative stress. In this study, we investigated the hypothesis that supplementation with cinnamon exerts an insulin sensitizer effect in patients with NAFLD. In a double-blind, placebo-controlled trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of cinnamon (each capsule contain 750 mg cinnamon) or 2 placebo capsules, daily for 12 weeks. During the intervention, all patients were given advice on how to implement a balanced diet and physical activity into their daily lives. In the treatment group (P < .05), significant decreases in HOMA (Homeostatic Model Assessment) index, FBS (fasting blood glucose), total cholesterol, triglyceride, ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma glutamine transpeptidase), and high-sensitivity C-reactive protein were seen, but there was no significant change in serum high-density lipoproteins levels (P = .122). In both groups, low-density lipoproteins decreased significantly (P < .05). In conclusion, the study suggests that taking 1500 mg cinnamon daily may be effective in improving NAFLD characteristics. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model.

    PubMed

    Ghlissi, Zohra; Hakim, Ahmed; Sila, Assaad; Mnif, Hela; Zeghal, Khaled; Rebai, Tarek; Bougatef, Ali; Sahnoun, Zouheir

    2014-05-01

    We evaluated the effect of astaxanthin (ASX) and vitamin E (vit E) on colistin methanesulfonate (CMS) induced-nephrotoxicity in rats. Animals were treated with sterile saline, 300000 or 450 000 IU/kg/day of CMS, CMS + ASX (20 mg/kg), CMS + vit E (100 mg/kg), or CMS + 1 ml/kg olive oil (OO) for 7 days. The plasma/urine creatinine (Cr) level, urine γ-glutamyl-transferase (GGT) level, and renal tissue activities in malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reductase (GSH), as well as renal histology were performed. CMS induced a tubular damage, increased the GGT and MDA levels, and decreased the activities of SOD, CAT, GPx and GSH. Co-treatment with ASX or vit E restored all biochemical parameters cited above and improved the histopathological damage. Nephrotoxicity induced by CMS might be due to oxidative damage. The improvement by ASX or vit E seems to be related to their antioxidant properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Chemical composition and biological evaluation of Physalis peruviana root as hepato-renal protective agent.

    PubMed

    El-Gengaihi, Souad E; Hassan, Emad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

    2013-03-01

    This study was designed to investigate the potential of Physalis peruviana root as a functional food with hepato-renal protective effects against fibrosis. The chemical composition of the plant root suggested the presence of alkaloids, withanolides and flavonoids. Five compounds were isolated and their structures elucidated by different spectral analysis techniques. One compound was isolated from the roots: cuscohygrine. The biological evaluation was conducted on different animal groups; control rats, control treated with ethanolic root extract, CCl(4) group, CCl(4) treated with root extract, and CCl(4) treated with silymarin as a standard herbal drug. The evaluation used the oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO). The liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea, and serum protein were also evaluated. The results suggested safe administration, and improvement of all the investigated parameters. The liver and kidney histopathological analysis confirmed the results. In conclusion, P. peruviana succeeded in protecting the liver and kidney against fibrosis. Further studies are needed to discern their pharmacological applications and clinical uses.

  17. The effect of silymarin on hepatic regeneration after partial hepatectomy: is silymarin effective in hepatic regeneration?

    PubMed Central

    Cetinkunar, Suleyman; Tokgoz, Serhat; Bilgin, Bulent Caglar; Erdem, Hasan; Aktimur, Recep; Can, Serpil; Erol, Huseyin Serkan; Isgoren, Atilla; Sozen, Selim; Polat, Yilmaz

    2015-01-01

    Aim: Silymarin from Silybum marianum was found to reduce liver injury. The aim of the present study was to investigate the effects of silymarin on hepatic regeneration in partially hepatectomized rats. Methods: Thirty Wistar-Albino rats were divided into 3 groups of 10 animals as sham, control and experimental groups. In the sham group (n=10) abdominal incision was closed after laparotomy. In the control group (n=10), the rats underwent 70% hepatectomy after laparotomy. In the experimental group (n=10) after partial 70% hepatectomy, silymarin (200 mg/kg/d) were given to rats for 10 days. Rats in three groups were sacrificed on 10 days. Aspartate (AST) and alanine transaminase (ALT), gamma glutamyl transferase (GGT), ALP, LDH and total bilirubin levels were measured using intracardiac blood samples. Tissue malondialdehyde (MDA) and tissue glutathion (GSH) and Superoxide dismutase (SOD) levels were measured. To reveal the increase in the mass of the remnant liver tissue in the control and experimental groups relative weight of the liver was calculated. Histopathological analysis of the liver was performed using a semi-quantitative scoring system. Results: A statistically significant difference among three groups was not shown for AST and ALT levels. A statistically significant difference was found between the groups as for total bilirubin and gamma glutamyl transferase levels. Increases in relative liver weights were seen with time in Groups 2 and 3. A statistically significant difference was not found for tissue malondialdehyde, Glutathion and Superoxide dismutase levels between hepatectomy and hepatectomy + silymarin groups. On liver tissue sections of the rats in the hepatectomy + silymarin group, increased regeneration and lipid peroxidation were observed accompanied by decreased antioxidant response. Conclusion: It has been observed that silymarin with many established functions such as antiproliferative, anti-inflammatory and energy antioxidant effects, does

  18. Diagnostic performance of traditional hepatobiliary biomarkers of drug-induced liver injury in the rat.

    PubMed

    Ennulat, Daniela; Magid-Slav, Michal; Rehm, Sabine; Tatsuoka, Kay S

    2010-08-01

    Nonclinical studies provide the opportunity to anchor biochemical with morphologic findings; however, liver injury is often complex and heterogeneous, confounding the ability to relate biochemical changes with specific patterns of injury. The aim of the current study was to compare diagnostic performance of hepatobiliary markers for specific manifestations of drug-induced liver injury in rat using data collected in a recent hepatic toxicogenomics initiative in which rats (n = 3205) were given 182 different treatments for 4 or 14 days. Diagnostic accuracy of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbili), serum bile acids (SBA), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total cholesterol (Chol), and triglycerides (Trig) was evaluated for specific types of liver histopathology by Receiver Operating Characteristic (ROC) analysis. To assess the relationship between biochemical and morphologic changes in the absence of hepatocellular necrosis, a second ROC analysis was performed on a subset of rats (n = 2504) given treatments (n = 152) that did not cause hepatocellular necrosis. In the initial analysis, ALT, AST, Tbili, and SBA had the greatest diagnostic utility for manifestations of hepatocellular necrosis and biliary injury, with comparable magnitude of area under the ROC curve and serum hepatobiliary marker changes for both. In the absence of hepatocellular necrosis, ALT increases were observed with biochemical or morphologic evidence of cholestasis. In both analyses, diagnostic utility of ALP and GGT for biliary injury was limited; however, ALP had modest diagnostic value for peroxisome proliferation, and ALT, AST, and total Chol had moderate diagnostic utility for phospholipidosis. None of the eight markers evaluated had diagnostic value for manifestations of hypertrophy, cytoplasmic rarefaction, inflammation, or lipidosis.

  19. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress

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

    Colacino, Justin A.; Arthur, Anna E.; Ferguson, Kelly K.

    Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003–2010 National Health and Nutrition Examination Survey to quantify diet's role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation bymore » multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. - Highlights: • Cadmium may cause chronic disease through oxidative stress or inflammation. • We developed a score to quantify dietary antioxidant and anti-inflammatory intake. • Cadmium was associated with markers of oxidative stress and inflammation. • Antioxidant and anti-inflammatory intake mitigated the effects of cadmium exposure. • Dietary interventions may be effective against chronic cadmium toxicity.« less

  20. The Hepatoprotective Effect of Vitamin A against Gasoline Vapor Toxicity in Rats

    PubMed Central

    Uboh, Friday E.; Ekaidem, Itemobong S.; Ebong, Patrick E.; Umoh, Ime B.

    2009-01-01

    Background Changes in the activities of plasma alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) are used to assess the functional state of the liver. Significant increase in the activities of these enzymes commonly indicates the hepatotoxicity of chemical agent(s) in the body. Exposure of male and female rats to 17.8 cm3h-1m-3 of Premium Motor Spirit (PMS) blend unleaded gasoline (UG) vapors for 6 hr/day, 5 days/week for 20 weeks have been observed to cause hepatotoxicity. In this study, the potential hepatoprotective effect of vitamin A (retinol) against gasoline vapours-induced toxicity was investigated in male and female rats. Methods Retinol (400 IU/kg/day) was orally administered to the test rats concomitant with the gasoline vapor exposure in the last two weeks of the experiment. Results The results obtained from this study showed that exposure to gasoline vapors caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in both male and female rats. The treatment of the male and female test rats with vitamin A produced a significant decrease (P < 0.05) in the activities of these parameters, compared with the test rats without treatment; but insignificant increase(P ≥ 0.05), compared with the control. Conclusions The result of this study demonstrates the beneficial effects of retinol, at prophylactic dosage, against gasoline vapours hepatotoxicity in male and female rats, thereby suggesting that retinol may be used to prevent hepatotoxicity in individuals frequently exposed to gasoline vapours. PMID:27933127

  1. Serum biomarkers for acute hepatotoxicity of Echis pyramidum snake venom in rats.

    PubMed

    Asmari, Abdulrahman K Al; Khan, Haseeb A; Banah, Faisal A; Buraidi, Ahmed A Al; Manthiri, Rajamohammed A

    2015-01-01

    Echis pyramidum is a venomous viper responsible for most cases of envenomation in Arabian Peninsula. We determined the acute phase (3-6 h) changes in serum markers of liver function including alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and bilirubin in adult male Sprague Dawley rats injected with Echis pyramidum venom (EPV) in the doses of 0.00 (control), 0.25, 0.50 and 1.00 mg/kg bodyweight. We also analyzed markers of oxidative stress including superoxide dismutase (SOD), catalase (CAT), total thiols (T-SH) and thiobarbituric acids reactive substances (TBARS) in liver. The results showed significant and dose- and time-dependent increases in serum ALT, ALP and GGT activities after a single injection of EPV. Serum bilirubin was significantly increased by medium and high doses of EVP after 3 h post-injection and then decreased at 6 h. The low dose of EPV neither affected the activity of SOD nor altered the levels of liver T-SH and TBARS, however, it significantly decreased the activity of CAT at 6 h post-injection of EPV. The medium dose of EPV significantly reduced liver SOD activity after 6 h whereas the high dose significantly reduced the SOD activity at 3 h and 6 h post-dosing. Both medium and high doses of EPV caused significant as well as dose- and time-dependent reductions in liver CAT activities. The high dose significantly reduced T-SH and increased TBARS in rat liver. Further studies are warranted to test the pharmacological potential of early phase antioxidant therapy for neutralizing the toxic effects of EPV.

  2. Assessment of Vitamin D status in a group of Egyptian children with non alcoholic fatty liver disease (multicenter study).

    PubMed

    Mohamed Ahmed, Amal; Abdel Ghany, Maha; Abdel Hakeem, Gehan Lotfy; Kamal, Aya; Khattab, Rania; Abdalla, Asmaa; Abou El Fotoh, Laila El Morsi; El Mazary, Abdel Azeem; Sayed, Madiha Abdalla; Abdel Fadil, Ashraf Mohamed

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the health problems with great burden on the liver that may end with liver cirrhosis and hepatocellular carcinoma. The aim of this work was to assess serum vitamin D level in nonalcoholic fatty liver disease children. This cross sectional case control study involved 47 patients with nonalcoholic fatty liver disease selected while recruiting the pediatric hepatology clinics. Their ages ranged from 5-15 years and were compared with 23 healthy age and sex matched children. All involved patients were subjected to careful history taking, clinical examination and for patients and control, anthropometric measures for body mass index (BMI) calculation (plotted on WHO percentile growth charts), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin (total and direct), serum albumin, creatinine, triglycerides, cholesterol, high density lipoprotein (HDL),low density lipoprotein (LDL), fasting blood glucose and fasting insulin (for calculation of insulin resistance), C reactive protein and serum vitamin D all were assayed. NAFLD was detected by ultrasonography and graded as absent, mild, moderate and severe. Ninety-three percent of NAFLD patients were obese. Significant differences were found between patients and control regarding AST, ALT, ALP, GGT, total and direct bilirubin, serum albumin, creatinine, triglycerides, cholesterol, HDL, fasting blood glucose, fasting insulin, the homeostatic model assessment for insulin resistance (HOMA-IR) and serum vitamin D levels. Significant negative correlation was found between serum vitamin D level and grades of steatosis. Serum vitamin D level decreases in children with NAFLD. This low serum vitamin D level is associated with higher stages of steatosis but not with BMI.

  3. Treatment with PPARδ agonist alleviates non-alcoholic fatty liver disease by modulating glucose and fatty acid metabolic enzymes in a rat model.

    PubMed

    Li, Xiuli; Li, Jin; Lu, Xiaolan; Ma, Huihui; Shi, Haitao; Li, Hong; Xie, Danhong; Dong, Lei; Liang, Chunlian

    2015-09-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition which is associated with certain features of metabolic syndrome and insulin resistance. Peroxisome proliferator‑activated receptor (PPAR)δ is an important regulator of energy metabolism and insulin resistance in diabetes. However, the function of PPARδ in NAFLD has not yet been fully elucidated. In the present study, in order to explore the function of PPARδ in NAFLD, we created a rat model of NALFD induced by a high-fat diet (HFD) and treated the rats with GW501516, a PPARδ agonist. We found that the lipid levels decreased, and hepatocellular ballooning and inflammatory cell infiltration were also significantly decreased following treatment of the rats with GW501516 compared to the untreated rats. Treatment with GW501516 also significantly decreased the homeostasis model assessment of insulin resistance (HOMA-IR) index, as well as the low‑density lipoprotein (LDL) levels. In addition, treatment with GW501516 increased the levels of insulin‑like growth factor‑1 (IGF-1) and high‑density lipoprotein (HDL) compared to the HFD group. Furthermore, the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) in the HFD group were all restored to the normal control levels following treatment with GW501516. RT‑qPCR and immunohistochemical staining revealed that the expression levels of sterol regulatory element binding protein‑1c (SREBP‑1c) and glucose transporter 2 (GLUT‑2) were both restored to normal control levels following treatment with GW501516. Also, the levels of enzymes related to lipid metabolism were increased following treatment with GW501516. In conclusion, our findings demonstrate that treatment with GW501516 alleviates NAFLD by modulating glucose and fatty acid metabolism.

  4. Antimetastatic potential of vernolide-A, a sesquiterpenoid from Vernonia cinerea L.

    PubMed

    Pratheeshkumar, P; Kuttan, Girija

    2012-01-01

    The inhibitory effect of vernolide-A (C(21)H(28)O(7)) on lung metastasis induced by B16F-10 melanoma cells was studied using C57BL/6 mice. Vernolide-A was administered in three different modalities such as simultaneously with tumor, prophylactic to tumor and after tumor development. Maximum inhibition in the metastasis was observed when vernolide-A was administered simultaneously with tumor. There was 89.39% inhibition of lung tumor nodule formation and 88.51% increase in the life span of metastatic tumor-bearing animals. Highly elevated levels of lung hydroxyproline, lung uronic acid, lung hexosamine, serum sialic acid, serum γ-glutamyl transpeptidase (GGT) and serum vascular endothelial growth factor (VEGF) in the metastatic control animals were found to be significantly lowered in the vernolide-A-treated animals. Histopathological analysis of lung tissues also correlated with these results. Vernolide-A administration downregulated the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, extracellular-signal-regulated kinase-1 (ERK-1), ERK-2 and VEGF in the lung tissue of B16F-10 melanoma challenged animals. In the in vitro system, vernolide-A showed a significant inhibition of invasion of B16F-10 melanoma cells across the collagen matrix. Vernolide-A treatment also inhibited the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. Vernolide-A could inhibit MMP-2 and MMP-9 protein expression in gelatin zymographic analysis of B16F-10 cells. (3)H-thymidine proliferation assay showed that vernolide-A could inhibit the proliferation of B16F-10 melanoma cells in vitro. These results indicate that vernolide-A could inhibit the metastatic progression of B16F-10 melanoma cells in mice.

  5. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity.

    PubMed

    Bellassoued, Khaled; Ghrab, Ferdaws; Makni-Ayadi, Fatma; Van Pelt, Jos; Elfeki, Abdelfattah; Ammar, Emna

    2015-01-01

    Kombucha (KT) is claimed to have various beneficial effects on human health, but there is very little scientific evidence available in the literature. The present study investigates the effects of Camellia sinensis (GT) Linn. (Theaceae) and KT, two natural drinks, on cholesterol and antioxidant status using a hypercholesterolemia rat model. The present study compared the free-radical scavenging abilities and polyphenol levels of GT and KT. Wistar rats fed cholesterol-rich diets were given KT or GT (5 mL/kg body weight per day, po) for 16 weeks, then fasted overnight and sacrificed. The plasma lipid levels, thiobarbituric acid reactive substances (TBARS) and aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGT) serum levels, antioxidant activities of superoxide dismutase (SOD) and catalase (CAT), and creatinine and urea rats were examined. KT had a phenolic compound of 955 ± 0.75 mg GAE/g) followed, by GT (788.92 ± 0.02 mg GAE/g). The free radical scavenging activity of KT was higher than GT. Compared with GT, KT induced lowered serum levels of TC, TG, VLDL-C, and LDL-C by 26, 27, 28, and 36%, respectively, and increased the serum level of high-density lipoprotein cholesterol (HDL-C). KT induced a 55% decrease of TBARS level in liver and 44% in kidney, compared with those of rats fed a cholesterol-rich diet alone. Moreover, CAT and SOD activities were reduced by 29 and 33%, respectively, in liver and 31 and 35%, respectively, in kidney, after oral administration of KT, compared with those of HCD-fed rats. The findings revealed that KT administration induced attractive curative effects on hypercholesterolemic, particularly in terms of liver-kidney functions in rats. Its effect on humans needs to be studied further.

  6. [The effect of diet ratio of polyunsaturated fatty acids of omega-3 and omega-6 families on activity of aminotransferases and gamma-glutamyltransferase in rat blood serum].

    PubMed

    Ketsa, O V; Marchenko, M M

    2014-01-01

    The effect of diet fat compositions with various ratio of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) activities in blood serum of 45 white mongrel rats weighing 90-110 g (9 animals in group) has been investigated. Fat components in the semi-synthetic diet, compiled on the basis of AIN-93 diet, and sources of omega-6 and omega-3 PUFA were presented by sunflower oil, soybean oil and fish oil. It has been shown that four-week inclusion of linoleic acid (LA) and alpha-linolenic acid (alpha-LNA) in a ratio of 7:1 into the diet (soybean oil) as well as use of only omega-6 PUFA (sunflower oil) has lead to an increase in the activity of ALT and GGT in rat blood serum compared to control animals treated with the complex of linolenic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid through the mixture of sunflower oil and fish oil (9:1) with the ratio of omega-6 and omega-3 PUFA 7:1. Along with this, the AST:ALT ratio (de Ritis ratio) was lower (p < 0.05) as compared with the control group of rat, amounting respectively 0.92 +/- 0.08 and 0.79 +/- 0.12 vs 1.26 +/- 0.10. The use of high doses of omega-3 fatty acids (600 mg EPA and 400 mg DHA per kg of animal weight per day coming through fish oil) did not affect the activity of ALT and GGT, but increased AST serum activity (0.47 +/- 0.04 micromoles/min per mg protein) and the de Ritis ratio (2.53 +/- 0.23). The diet deprived with fat increased enzyme activity of ALT, AST and GGT in rat blood serum.

  7. Persistent hypertransaminasemia in asymptomatic children: A stepwise approach

    PubMed Central

    Vajro, Pietro; Maddaluno, Sergio; Veropalumbo, Claudio

    2013-01-01

    We aimed to examine the major causes of isolated chronic hypertransaminasemia in asymptomatic children and develop a comprehensive diagnostic flow diagram. A MEDLINE search inclusive of publications throughout August 2012 was performed. We found only a small number of publications that had comprehensively investigated this topic. Consequently, it was difficult to construct a diagnostic flowchart similar to those already available for adults. In children, a “retesting panel” prescription, including gamma-glutamyl transpeptidase and creatine kinase in addition to aminotransferases, is considered a reasonable approach for proficiently confirming the persistence of the abnormality, ruling out cholestatic hepatopathies and myopathies, and guiding the subsequent diagnostic steps. If re-evaluation of physical and historical findings suggests specific etiologies, then these should be evaluated in the initial enzyme retesting panel. A simple multi-step diagnostic algorithm incorporating a large number of possible pediatric scenarios, in addition to the few common to adults, is available. Accurately classifying a child with asymptomatic persistent hypertransaminasemia may be a difficult task, but the results are critical for preventing the progression of an underlying, possibly occult, condition later in childhood or during transition. Given the high benefit/cost ratio of preventing hepatic deterioration, no effort should be spared in diagnosing and properly treating each case of persistent hypertransaminasemia in pediatric patients. PMID:23687411

  8. Physiological and psychosocial factors that predict HIV-related fatigue.

    PubMed

    Barroso, Julie; Hammill, Bradley G; Leserman, Jane; Salahuddin, Naima; Harmon, James L; Pence, Brian Wells

    2010-12-01

    Fatigue is one of the most common and debilitating symptoms experienced by HIV-infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue.

  9. The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid improves the biliary cirrhosis in the rat.

    PubMed

    Fernández-Martínez, Eduardo; Pérez-Hernández, Nury; Muriel, Pablo; Pérez-Alvarez, Víctor; Shibayama, Mineko; Tsutsumi, Víctor

    2009-09-01

    Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.

  10. Improved expression, purification and crystallization of a putative N-acetyl-γ-glutamyl-phosphate reductase from rice (Oryza sativa)

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

    Miura-Ohnuma, Jun; Nonaka, Tsuyoshi; Katoh, Shizue

    2005-12-01

    Crystals of OsAGPR were obtained using the sitting-drop vapour-diffusion method at 293 K and diffract X-rays to at least 1.8 Å resolution. They belong to the hexagonal space group P6{sub 1}, with unit-cell parameters a = 86.11, c = 316.3 Å. N-Acetyl-γ-glutamyl-phosphate reductase (AGPR) catalyzes the third step in an eight-step arginine-biosynthetic pathway that starts with glutamate. This enzyme converts N-acetyl-γ-glutamyl phosphate to N-acetylglutamate-γ-semialdehyde by an NADPH-dependent reductive dephosphorylation. AGPR from Oryza sativa (OsAGPR) was expressed in Escherichia coli at 291 K as a soluble fusion protein with an upstream thioredoxin-hexahistidine [Trx-(His){sub 6}] extension. OsAGPR(Ala50–Pro366) was purified and crystals weremore » obtained using the sitting-drop vapour-diffusion method at 293 K and diffract X-rays to at least 1.8 Å resolution. They belong to the hexagonal space group P6{sub 1}, with unit-cell parameters a = 86.11, c = 316.3 Å.« less

  11. Crystal structure of Bacillus anthracis transpeptidase enzyme CapD.

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

    Wu, R.; Richter, S.; Zhang, R.

    2009-09-04

    Bacillus anthracis elaborates a poly-{gamma}-d-glutamic acid capsule that protects bacilli from phagocytic killing during infection. The enzyme CapD generates amide bonds with peptidoglycan cross-bridges to anchor capsular material within the cell wall envelope of B. anthracis. The capsular biosynthetic pathway is essential for virulence during anthrax infections and can be targeted for anti-infective inhibition with small molecules. Here, we present the crystal structures of the {gamma}-glutamyltranspeptidase CapD with and without {alpha}-l-Glu-l-Glu dipeptide, a non-hydrolyzable analog of poly-{gamma}-d-glutamic acid, in the active site. Purified CapD displays transpeptidation activity in vitro, and its structure reveals an active site broadly accessible for poly-{gamma}-glutamatemore » binding and processing. Using structural and biochemical information, we derive a mechanistic model for CapD catalysis whereby Pro{sup 427}, Gly{sup 428}, and Gly{sup 429} activate the catalytic residue of the enzyme, Thr{sup 352}, and stabilize an oxyanion hole via main chain amide hydrogen bonds.« less

  12. Fasting conditions: Influence of water intake on clinical chemistry analytes.

    PubMed

    Benozzi, Silvia F; Unger, Gisela; Campion, Amparo; Pennacchiotti, Graciela L

    2018-02-15

    Currently available recommendations regarding fasting requirements before phlebotomy do not specify any maximum water intake volume permitted during the fasting period. The aim was to study the effects of 300 mL water intake 1 h before phlebotomy on specific analytes. Blood was collected from 20 women (median age (min-max): 24 (22 - 50) years) in basal state (T 0 ) and 1 h after 300 mL water intake (T 1 ). Glucose, total proteins (TP), urea, creatinine, cystatin C, total bilirubin (BT), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (Tg), uric acid (UA), high-sensitivity C-reactive protein, gamma-glutamyl transferase (GGT), aspartate-aminotransferase (AST), alanine-aminotransferase and lactate-dehydrogenase (LD) were studied. Results were analyzed using Wilcoxon test. Mean difference (%) was calculated for each analyte and was further compared with reference change value (RCV). Only mean differences (%) higher than RCV were considered clinically significant. Significant differences (median T 0 vs median T 1 , P) were observed for TP (73 vs 74 g/L, 0.001); urea (4.08 vs 4.16 mmol/L, 0.010); BT (12 vs 13 µmol/L, 0.021); total cholesterol (4.9 vs 4.9 mmol/L, 0.042); Tg (1.05 vs 1.06 mmol/L, 0.002); UA (260 vs 270 µmol/L, 0.006); GGT (12 vs 12 U/L, 0.046); AST (22 vs 24 U/L, 0.001); and LD (364 vs 386 U/L, 0.001). Although the differences observed were statistically significant, they were not indicative of clinically significant changes. A water intake of 300 mL 1 h prior to phlebotomy does not interfere with the analytes studied in the present work.

  13. Clinical Characteristics and Outcome of Hepatic Sarcoidosis: A Population-Based Study 1976-2013.

    PubMed

    Ungprasert, Patompong; Crowson, Cynthia S; Simonetto, Douglas A; Matteson, Eric L

    2017-10-01

    Data on clinical manifestations and outcome of hepatic sarcoidosis are scarce. This study aimed to use a population-based cohort of patients with incident sarcoidosis to better describe the characteristics of hepatic sarcoidosis. A cohort of incident cases of sarcoidosis in Olmsted County, MN, USA, from 1976 to 2013 was identified from the database. Diagnosis was verified by individual medical record review. Confirmed cases of sarcoidosis were then reviewed for liver involvement. Data on clinical manifestations, imaging study, liver biochemical tests, treatment, and outcome were collected. Cumulative incidence of cirrhosis adjusted for the competing risk of death was estimated. A total of 345 cases of incident sarcoidosis were identified. Of these, 19 cases (6%) had liver involvement (mean age 46.1 years, 53% female and 79% Caucasian). Most patients had asymptomatic liver disease and were discovered in pursuit of abnormal biochemical tests and imaging studies. Alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were elevated in the majority of patients (88 and 90%, respectively). Elevated transaminases were less common and less severe. About half of patients had abnormal imaging study with hypodense nodular lesions being the most common abnormality (six patients) followed by hepatomegaly (three patients). Liver biopsy revealed non-caseating granuloma in 88% (14 of 16 patients). A total of four patients developed cirrhosis. Involvement of the liver by sarcoidosis was seen in 6% of patients with sarcoidosis. The majority of patients were asymptomatic. Elevated ALP and GGT were the most common abnormal biochemical tests. Liver biopsy revealed non-caseating granuloma in almost all cases. Cirrhosis was seen in a significant number of patients. Generalizability of the observations to other populations may be limited, as the studied population was predominantly Caucasian. The prevalence of liver disease may be higher in more diverse populations.

  14. The relationship between the parenteral dose of fish oil supplementation and the variation of liver function tests in hospitalized adult patients.

    PubMed

    Badia-Tahull, Maria B; Leiva-Badosa, Elisabet; Jodar-Masanes, Ramon; Ramon-Torrell, Josep Maria; Llop-Talaveron, Josep

    2015-07-02

    Hepatic dysfunction is a complication associated with parenteral nutrition (PN). Our primary objective was to study the relationship between doses of intravenous fish oil (FO) emulsion in PN and the variation in the main liver function tests (LFTs) in hospitalized PN-treated adults. As a secondary objective, we studied the safety of FO administration. We conducted a retrospective study in adult patients receiving FO supplementation in PN. Demographic, nutritional and safety variables were collected. Variation of LFTs was defined as the difference between values just before the first administration of FO and values at the end of PN. A multiple linear regression was performed to study the association between PN-lipids (FO or vegetable) and the variation of each LFT; the following variables were used to adjust the effect of lipids: sepsis, length of stay in the intensive care unit and lipids dose. Student t-test was used to study safety variables. Data were analyzed using SPSS 19.0. Patients (53, median age 68 years (24-90); 62% men) with the principal diagnosis of digestive neoplasm (42%) received PN for a median of 19 (7-75) days. In the multivariate analysis, the amount of FO was related to a decrease in gamma-glutamyl transferase (GGT) (B = -2.23;CI95 % = -4.41/-0.05), a decrease in alkaline phosphatase (AP) (B = -1.23;CI95 % = -2.07/-0.37), and a decrease in alanine aminotransferase (ALT) (B = -0.82; CI95 % = -1.19/-0.44). No differences were found in safety variables. GGT, AP and ALT improved with FO PN-supplementation. Moreover, the improvement was greater when the doses of FO were higher. FO administration in PN is safe.

  15. Oxidative stress response of Forster's terns (Sterna forsteri) and Caspian terns (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney, and brain

    USGS Publications Warehouse

    Hoffman, David J.; Eagles-Smith, Collin A.; Ackerman, Joshua T.; Adelsbach, Terrence L.; Stebbins, Katherine R.

    2011-01-01

    Bioindicators of oxidative stress were examined in prebreeding and breeding adult and chick Forster's terns (Sterna forsteri) and in prebreeding adult Caspian terns (Hydroprogne caspia) in San Francisco Bay, California. Highest total mercury (THg) concentrations (mean±standard error;μg/g dry wt) in liver (17.7±1.7), kidney (20.5±1.9), and brain (3.0±0.3) occurred in breeding adult Forster's terns. The THg concentrations in liver were significantly correlated with hepatic depletion of reduced glutathione (GSH), increased oxidized glutathione (GSSG):GSH ratio, and decreased hepatic gamma-glutamyl transferase (GGT) activity in adults of both tern species. Prefledging Forster's tern chicks with one-fourth the hepatic THg concentration of breeding adults exhibited effects similar to adults. Total mercury-related renal GSSG increased in adults and chicks. In brains of prebreeding adults, THg was correlated with a small increase in glucose-6-phosphate dehydrogenase (G-6-PDH) activity, suggestive of a compensatory response. Brain THg concentrations were highest in breeding adult Forster's terns and brain tissue exhibited increased lipid peroxidation as thiobarbituric acid-reactive substances, loss of protein bound thiols (PBSH), and decreased activity of antioxidant enzymes, GSSG reductase (GSSGrd), and G-6-PDH. In brains of Forster's tern chicks there was a decrease in total reduced thiols and PBSH. Multiple indicator responses also pointed to greater oxidative stress in breeding Forster's terns relative to prebreeding terns, attributable to the physiological stress of reproduction. Some biondicators also were related to age and species, including thiol concentrations. Enzymes GGT, G-6-PDH, and GSSGred activities were related to species. Our results indicate that THg concentrations induced oxidative stress in terns, and suggest that histopathological, immunological, and behavioral effects may occur in terns as reported in other species.

  16. Mitochondrial and cytoplasmic isoleucyl-, glutamyl- and arginyl-tRNA synthetases of yeast are encoded by separate genes.

    PubMed

    Tzagoloff, A; Shtanko, A

    1995-06-01

    Three complementation groups of a pet mutant collection have been found to be composed of respiratory-deficient deficient mutants with lesions in mitochondrial protein synthesis. Recombinant plasmids capable of restoring respiration were cloned by transformation of representatives of each complementation group with a yeast genomic library. The plasmids were used to characterize the complementing genes and to institute disruption of the chromosomal copies of each gene in respiratory-proficient yeast. The sequences of the cloned genes indicate that they code for isoleucyl-, arginyl- and glutamyl-tRNA synthetases. The properties of the mutants used to obtain the genes and of strains with the disrupted genes indicate that all three aminoacyl-tRNA synthetases function exclusively in mitochondrial proteins synthesis. The ISM1 gene for mitochondrial isoleucyl-tRNA synthetase has been localized to chromosome XVI next to UME5. The MSR1 gene for the arginyl-tRNA synthetase was previously located on yeast chromosome VIII. The third gene MSE1 for the mitochondrial glutamyl-tRNA synthetase has not been localized. The identification of three new genes coding for mitochondrial-specific aminoacyl-tRNA synthetases indicates that in Saccharomyces cerevisiae at least 11 members of this protein family are encoded by genes distinct from those coding for the homologous cytoplasmic enzymes.

  17. γ-Glutamyltransferase Fractions in Obese Subjects with Type 2 Diabetes: Relation to Insulin Sensitivity and Effects of Bariatric Surgery.

    PubMed

    Franzini, Maria; Musetti, Veronica; Guarino, Daniela; Caponi, Laura; Paolicchi, Aldo; Emdin, Michele; Ferrannini, Ele; Nannipieri, Monica

    2018-05-01

    Gamma-glutamyltranspeptidase (GGT) levels are an independent risk marker for the development of type 2 diabetes (T2DM). We investigated the relationship between the newly identified serum GGT fractions and glucose metabolism in obese subjects before and after bariatric surgery. Twenty-nine T2DM subjects, wait-listed for Roux-en-Y gastric bypass (RYGB; n = 21) or laparoscopic sleeve gastrectomy (LSG; n = 8), received a 5-h mixed meal test before (T0), 15 days (T15), and 1 year after surgery (T365). Insulin sensitivity was assessed by the OGIS index and β-cell function by C-peptide analysis; fractional GGT (b-, s-, m-, and f-GGT) analysis was performed by gel-filtration chromatography. At T15, total GGT activity decreased by 40% after LSG (p = 0.007) but remained unchanged after RYGB. At T365, all patients showed a reduction in total GGT, in particular b-GGT (≥ 60%) and m-GGT (≥ 50%). In patients with biopsy-proven steatohepatitis (n = 10), total, b-, s-, and m-GGT fractions at T0 were significantly higher than in patients with low-grade steatosis (p = 0.016, 0.0003, and 0.005, respectively); at T365, there was a significant fall in total GGT as well as in each fraction in both groups. In a multiple regression model, b-GGT was the only fraction related to insulin sensitivity (p = 0.016; β coeff. = - 14.0) independently of BMI, fasting glucose, and triglycerides. While GGT activity is generally associated with impaired glucose metabolism, fractional GGT analysis showed that the b-GGT fraction specifically and independently tracks with insulin resistance.

  18. Serotonergic neurotoxic metabolites of ecstasy identified in rat brain.

    PubMed

    Jones, Douglas C; Duvauchelle, Christine; Ikegami, Aiko; Olsen, Christopher M; Lau, Serrine S; de la Torre, Rafael; Monks, Terrence J

    2005-04-01

    The selective serotonergic neurotoxicity of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) depends on their systemic metabolism. We have recently shown that inhibition of brain endothelial cell gamma-glutamyl transpeptidase (gamma-GT) potentiates the neurotoxicity of both MDMA and MDA, indicating that metabolites that are substrates for this enzyme contribute to the neurotoxicity. Consistent with this view, glutathione (GSH) and N-acetylcysteine conjugates of alpha-methyl dopamine (alpha-MeDA) are selective neurotoxicants. However, neurotoxic metabolites of MDMA or MDA have yet to be identified in brain. Using in vivo microdialysis coupled to liquid chromatography-tandem mass spectroscopy and a high-performance liquid chromatography-coulometric electrode array system, we now show that GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA are present in the striatum of rats administered MDMA by subcutaneous injection. Moreover, inhibition of gamma-GT with acivicin increases the concentration of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA in brain dialysate, and there is a direct correlation between the concentrations of metabolites in dialysate and the extent of neurotoxicity, measured by decreases in serotonin (5-HT) and 5-hydroxyindole acetic (5-HIAA) levels. Importantly, the effects of acivicin are independent of MDMA-induced hyperthermia, since acivicin-mediated potentiation of MDMA neurotoxicity occurs in the context of acivicin-mediated decreases in body temperature. Finally, we have synthesized 5-(N-acetylcystein-S-yl)-N-methyl-alpha-MeDA and established that it is a relatively potent serotonergic neurotoxicant. Together, the data support the contention that MDMA-mediated serotonergic neurotoxicity is mediated by the systemic formation of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA (and alpha-MeDA). The mechanisms by which such metabolites access the brain and produce selective

  19. Combined therapy with danazol, pegilated interferon, and ribavirin improves thrombocytopenia and liver injury in rats with fibrosis.

    PubMed

    Alvarez, Guillermo Cabrera; Madrid-Marina, Vicente; Jimenez-Mendez, Ricardo; Buitimea, Angel Leon; Román, Margarita Bahena; Cortez-Gomez, Rudyard; Esparza, Jorge Reyes; Rodríguez-Fragoso, Lourdes

    2007-01-01

    The aim of this study was to investigate the effects of combinations of pegilated-interferon (PEG-IFN), ribavirin, and danazol on thrombocytopenia and liver injury in rats with fibrosis. Male adult Wistar rats were treated with either mineral oil, danazol (0.83 mg/kg per day), PEG-interferon alpha-2a (PEG-IFN, 0.3 microg/ week) + ribavirin (12 mg/kg per day), PEG-IFN + ribavirin + danazol, CCl(4) (4 g/kg for eight weeks), CCl(4) + PEG-IFN + ribavirin, or CCl(4) + PEG-IFN + ribavirin+ danazol. The following assays were conducted: hematology, clinical chemistry, liver function, liver fibrosis, lymphocyte cytokine mRNA expression, and bone-marrow DNA content. Platelet counts were low in sham-treated animals and animals treated with PEG- IFN + ribavirin (30% and 25% respectively; P < 0.05). PEG-IFN + ribavirin + danazol reduced platelet counts of fibrotic animals by only 9% (P < 0.05). PEG- IFN + ribavirin reduced hepatic collagen content by 50%, whereas danazol + PEG-IFN + ribavirin reduced hepatic collagen content by 60% (P < 0.05). PEG-IFN + ribavirin reduced the total bilirubin concentration by 27%, alanine amino transferase (ALT) activity by 75% and gamma-glutamyl transpeptidase (gamma-GTP) activity by 74% (P < 0.05). In contrast, danazol + PEG-IFN + ribavirin reduced total bilirubin levels by 61%, alkaline phosphatase activity by 45%, ALT activity by 76%, and gamma-GTP activity by 74% (P < 0.05). The only treatment that increased interleukin 10 (IL-10) mRNA in fibrotic rats was PEG-IFN + ribavirin. However, danazol + PEG-IFN + ribavirin reduced the expression of IL-6, IL-10, tumor necrosis factor alpha and transforming growth factor ss. Bone-marrow DNA content was not altered by any treatment. In conclusion, PEG-IFN + ribavirin + danazol could be a new therapeutic option for patients with liver injury, fibrosis, and thrombocytopenia.

  20. γ-PGA and MTGase improve the formation of ε-(γ-glutamyl) lysine cross-links within hairtail (Trichiurus haumela) surimi protein.

    PubMed

    Hu, Yaqin; Shao, Ying; Wu, Chunhua; Yuan, Chunhong; Ishimura, Gakushi; Liu, Wenjuan; Chen, Shiguo

    2018-03-01

    The present study investigated the mechanism of ε-(γ-glutamyl) lysine cross-links within hairtail (Trichiurus haumela) surimi protein via γ-polyglutamic acid (γ-PGA) and MTGase. The results indicated that the addition of MTGase and γ-PGA markedly improved the gelation properties of hairtail surimi protein, including its maximum breaking force and deformation, water holding capacity and gel strength. The maximum improvements were achieved by adding 0.5units MTGase/g meat paste in combination with 0.06% γ-PGA. SDS-PAGE showed that the band intensity of cross-linked proteins increased, whereas that of myosin heavy chain decreased after treatments. Further scanning electron microscopy (SEM) analysis showed the formation of a denser gel matrix, which was caused by much stronger and more inter- and intra-molecular cross-linking of proteins, via MTGase catalysing ε-(γ-glutamyl) lysine cross-links formed between lysine residues in the gel protein and glutamic residues in the hydrolytic γ-PGA. The results provide reliable guidance for the improvement of hairtail surimi protein gelation properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Structure and Inhibitor Specificity of L,D-Transpeptidase (LdtMt2) from Mycobacterium tuberculosis and Antibiotic Resistance: Calcium Binding Promotes Dimer Formation.

    PubMed

    Gokulan, Kuppan; Khare, Sangeeta; Cerniglia, Carl E; Foley, Steven L; Varughese, Kottayil I

    2018-03-09

    The final step of peptidoglycan (PG) synthesis in all bacteria is the formation of cross-linkage between PG-stems. The cross-linking between amino acids in different PG chains gives the peptidoglycan cell wall a 3-dimensional structure and adds strength and rigidity to it. There are two distinct types of cross-linkages in bacterial cell walls. D,D-transpeptidase (D,D-TPs) generate the classical 4➔3 cross-linkages and the L,D-transpeptidase (L,D-TPs) generate the 3➔3 non-classical peptide cross-linkages. The present study is aimed at understanding the nature of drug resistance associated with L,D-TP and gaining insights for designing novel antibiotics against multi-drug resistant bacteria. Penicillin and cephalosporin classes of β-lactams cannot inhibit L,D-TP function; however, carbapenems inactivate its function. We analyzed the structure of L,D-TP of Mycobacterium tuberculosis in the apo form and in complex with meropenem and imipenem. The periplasmic region of L,D-TP folds into three domains. The catalytic residues are situated in the C-terminal domain. The acylation reaction occurs between carbapenem antibiotics and the catalytic Cys-354 forming a covalent complex. This adduct formation mimics the acylation of L,D-TP with the donor PG-stem. A novel aspect of this study is that in the crystal structures of the apo and the carbapenem complexes, the N-terminal domain has a muropeptide unit non-covalently bound to it. Another interesting observation is that the calcium complex crystallized as a dimer through head and tail interactions between the monomers.

  2. d-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats.

    PubMed

    Bacanlı, Merve; Anlar, Hatice Gül; Aydın, Sevtap; Çal, Tuğbagül; Arı, Nuray; Ündeğer Bucurgat, Ülkü; Başaran, A Ahmet; Başaran, Nurşen

    2017-12-01

    It is known that diabetes causes some complications including alterations in lipid profile, hepatic enzyme levels but also it causes oxidative stress. Limonene, a major component of Citrus oils, has important health beneficial effects in lowering the level of oxidative stress due to its antioxidant activity. The aim of this study was to investigate the effects of D-limonene on streptozotocin (STZ)-induced diabetes in Wistar albino rats. For this purpose, DNA damage was evaluated by alkaline comet assay. Changes in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSHPx) and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), total glutathione (GSH), malondialdehyde (MDA), insulin, total bilirubin and BCA protein, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglyceride were also evaluated. D-limonene treatment was found to significantly decrease DNA damage, GR enzyme activities and MDA levels and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities and altered lipid and liver enzyme parameters in diabetic rats. According to our results, it seems that D-limonene might have a role in the prevention of the complication of diabetes in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Quality specifications for the extra-analytical phase of laboratory testing: Reference intervals and decision limits.

    PubMed

    Ceriotti, Ferruccio

    2017-07-01

    Reference intervals and decision limits are a critical part of the clinical laboratory report. The evaluation of their correct use represents a tool to verify the post analytical quality. Four elements are identified as indicators. 1. The use of decision limits for lipids and glycated hemoglobin. 2. The use, whenever possible, of common reference values. 3. The presence of gender-related reference intervals for at least the following common serum measurands (besides obviously the fertility relate hormones): alkaline phosphatase (ALP), alanine aminotransferase (ALT), creatine kinase (CK), creatinine, gamma-glutamyl transferase (GGT), IgM, ferritin, iron, transferrin, urate, red blood cells (RBC), hemoglobin (Hb) and hematocrit (Hct). 4. The presence of age-related reference intervals. The problem of specific reference intervals for elderly people is discussed, but their use is not recommended; on the contrary it is necessary the presence of pediatric age-related reference intervals at least for the following common serum measurands: ALP, amylase, creatinine, inorganic phosphate, lactate dehydrogenase, aspartate aminotransferase, urate, insulin like growth factor 1, white blood cells, RBC, Hb, Hct, alfa-fetoprotein and fertility related hormones. The lack of such reference intervals may imply significant risks for the patients. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Hematology, plasma biochemistry, and tissue enzyme activities of invasive red lionfish captured off North Carolina, USA.

    PubMed

    Anderson, E T; Stoskopf, M K; Morris, J A; Clarke, E O; Harms, C A

    2010-12-01

    The red lionfish Pterois volitans is important not only in the aquarium trade but also as an invasive species in the western Atlantic. Introduced to waters off the southeastern coast of the United States, red lionfish have rapidly spread along much of the East Coast and throughout Bermuda, the Bahamas, and much of the Caribbean. Hematology and plasma biochemistry were evaluated in red lionfish captured from the offshore waters of North Carolina to establish baseline parameters for individual and population health assessment. Blood smears were evaluated for total and differential white blood cell counts, and routine clinical biochemical profiles were performed on plasma samples. To improve the interpretive value of routine plasma biochemistry profiles, tissue enzyme activities (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], lactate dehydrogenase [LD], and creatine kinase [CK]) were analyzed from liver, kidney, skeletal muscle, gastrointestinal tract, and heart tissues from five fish. The hematological and plasma biochemical values were similar to those of other marine teleosts except that the estimated white blood cell counts were much lower than those routinely found in many species. The tissue enzyme activity findings suggest that plasma LD, CK, and AST offer clinical relevance in the assessment of red lionfish.

  5. mTORC1 inhibitors rapamycin and metformin affect cardiovascular markers differentially in ZDF rats.

    PubMed

    Nistala, Ravi; Raja, Ahmad; Pulakat, Lakshmi

    2017-03-01

    Mammalian target for rapamycin complex 1 (mTORC1) is a common target for the action of immunosuppressant macrolide rapamycin and glucose-lowering metformin. Inhibition of mTORC1 can exert both beneficial and detrimental effects in different pathologies. Here, we investigated the differential effects of rapamycin (1.2 mg/kg per day delivered subcutaneously for 6 weeks) and metformin (300 mg/kg per day delivered orally for 11 weeks) treatments on male Zucker diabetic fatty (ZDF) rats that mimic the cardiorenal pathology of type 2 diabetic patients and progress to insulin insufficiency. Rapamycin and metformin improved proteinuria, and rapamycin also reduced urinary gamma glutamyl transferase (GGT) indicating improvement of tubular health. Metformin reduced food and water intake, and urinary sodium and potassium, whereas rapamycin increased urinary sodium. Metformin reduced plasma alkaline phosphatase, but induced transaminitis as evidenced by significant increases in plasma AST and ALT. Metformin also induced hyperinsulinemia, but did not suppress fasting plasma glucose after ZDF rats reached 17 weeks of age, and worsened lipid profile. Rapamycin also induced mild transaminitis. Additionally, both rapamycin and metformin increased plasma uric acid and creatinine, biomarkers for cardiovascular and renal disease. These observations define how rapamycin and metformin differentially modulate metabolic profiles that regulate cardiorenal pathology in conditions of severe type 2 diabetes.

  6. Influence of thermal processing on hydrolysis and stability of folate poly-gamma-glutamates in broccoli (Brassica oleracea var. italica), carrot (Daucus carota) and tomato (Lycopersicon esculentum).

    PubMed

    Munyaka, Ann Wambui; Verlinde, Philippe; Mukisa, Ivan Muzira; Oey, Indrawati; Van Loey, Ann; Hendrickx, Marc

    2010-04-14

    The folate poly-gamma-glutamate profile, their concentrations, and hydrolysis by endogenous gamma-glutamyl hydrolase (GGH) were evaluated in broccoli, carrot and tomato. Further studies on the effect of time and temperature on folate poly-gamma-glutamate hydrolysis and stability were carried out in broccoli since this vegetable showed the highest long-chain and total folate poly-gamma-glutamate concentration. The evolution of l-ascorbic acid, total phenols and Trolox equivalent antioxidant capacity (TEAC) values was evaluated in parallel. Upon thermal inactivation of GGH prior to crushing, it was observed that broccoli, carrot and tomato contained poly-gamma-glutamates with one to seven glutamate residues but differed in the predominant poly-gamma-glutamates. Crushing of raw broccoli, carrot and tomato resulted in significant poly-gamma-glutamate profile changes in broccoli and carrot (indicating GGH-catalyzed hydrolysis) but not in tomato. In this study, the actual crushing of raw broccoli matrix had a greater effect on folate poly-gamma-glutamate hydrolysis than incubation conditions (0-30 min at 25-55 degrees C). During treatments at 25-140 degrees C, folate retention was higher at 80 and 100 degrees C than at the other temperatures. A similar trend in thermal stability was observed for folates, vitamin C, total phenols and TEAC value, an indication that conditions that result in endogenous antioxidants degradation might also result in folate degradation.

  7. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  8. Physiological and Psychosocial Factors that Predict HIV-Related Fatigue

    PubMed Central

    Hammill, Bradley G.; Leserman, Jane; Salahuddin, Naima; Harmon, James L.; Pence, Brian Wells

    2010-01-01

    Fatigue is one of the most common and debilitating symptoms experienced by HIV-infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue. PMID:20352317

  9. Determinants of platelet aggregation in 50-70-year-old men from three Japanese communities.

    PubMed

    Imano, Hironori; Iso, Hiroyasu; Sato, Shinichi; Kitamura, Akihiko; Okamura, Tomonori; Tanigawa, Takeshi; Ohira, Tetsuya; Kudo, Minako; Naito, Yoshihiko; Iida, Minoru; Shimamoto, Takashi

    2002-12-01

    To investigate the association of lifestyle and constitutional variables with platelet aggregation, we examined the platelet aggregation, serum fatty acid composition, alcohol intake, smoking, and dietary intake of seafood and soybean estimated by a 1-week dietary record in 448 males aged 50-70 in three rural Japanese communities: Ikawa, Akita prefecture (northeast coast), Noichi, Kochi prefecture (southwest coast), and Kyowa, Ibaraki prefecture (central inland). Platelet aggregatory threshold index (PATI) was used to determine the minimum concentration of adenosine 5'-diphosphate (ADP) that caused a non-reversible aggregation of platelets. Intake of seafood and n3-polyunsaturated fatty acid and ingestion of ethanol were higher in the northeast coastal community than in the other two communities. Mean platelet and white blood cell counts were lower in northeast coastal community than in the other two communities. The geometric mean PATI was higher (i.e. platelet aggregation was lower) in the northeast coastal community than the other two communities. Within the entire sample, platelet aggregation correlated inversely with serum level of n3-polyunsaturated fatty acids and gamma-glutamyl transpeptidase, an index of alcohol consumption, and positively with platelet and white blood cell counts. Platelet aggregation tended to correlate positively with serum arachidonic acid. There was no correlation between smoking and platelet aggregation. Our results suggest that seafood intake and moderate alcohol consumption reduce platelet aggregation.

  10. The health and social effects of drinking water-based infusions of kava: a review of the evidence.

    PubMed

    Rychetnik, Lucie; Madronio, Christine M

    2011-01-01

    To review the evidence on the health and social effects of drinking kava; a water-based infusion of the roots of the kava plant. Included all empirical studies of the effects of kava published 1987-2008 reporting health and social outcomes. Evidence appraised on study design (level of evidence) and standard epidemiological criteria for causality. Causality indicated: scaly skin rash, weight loss, raised Gamma Glutamyl Transpeptidase liver enzyme levels, nausea, loss of appetite or indigestion; Association indicated but causality unclear: red sore eyes, impotence or loss of sexual drive, self-reported poor health, raised cholesterol, and loss of time and money, low motivation and 'slow/lazy' days following use, reduced alcohol consumption and related violence; Association hypothesised: fits or seizures, Melioidosis, Ischaemic Heart Disease, protective effects for cancer; No association indicated: cognitive performance; No association suggested: cognitive impairment, liver toxicity or permanent liver damage, other pneumonia; No association hypothesised: hallucinations. The health and social implications of chronic kava drinking can be significant for individuals and communities, although most effects of even heavy consumption appear to be reversible when consumption is stopped. An Australia-wide ban on commercial importation of kava has been in place since mid-2007, but there is no published literature to date on the impact of the ban. © 2010 Australasian Professional Society on Alcohol and other Drugs.

  11. Therapeutic efficacy of DL-alpha-lipoic acid on cyclosporine A induced renal alterations.

    PubMed

    Amudha, Ganapathy; Josephine, Anthony; Mythili, Yenjerla; Sundarapandiyan, Rajaguru; Varalakshmi, Palaninathan

    2007-10-01

    The present study was designed to evaluate the possible beneficial effect of lipoic acid in preventing the renal damage induced by cyclosporine A in rats. Male albino rats of Wistar strain were divided into four groups and treated as follows. Two groups received cyclosporine A by oral gavage (25 mg/kg/body weight) for 21 days to induce nephrotoxicity, one of which simultaneously received lipoic acid treatment (20 mg/kg body weight) for 21 days. A vehicle (olive oil) and a lipoic acid drug control were also included. Cyclosporine A induced renal damage was evident from the decreased activities of tissue marker enzymes (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and decreased activities of ATPases (Na+, K+-ATPase, Ca2+-ATPase and Mg2+ ATPase). An apparent increase in the levels of serum constituents (urea, uric acid and creatinine) and urinary marker enzymes (N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galactosidase, cathepsin-D and gamma-glutamyl transpeptidase) along with significant decline in creatinine clearance were seen in the cyclosporine treated rats, which was reversed upon treatment with lipoic acid. Ultrastructural observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the morphological lesions in renal tissue. Hence, this study clearly exemplifies that lipoic acid might be an ideal choice against cyclosporine A induced cellular abnormalities.

  12. Long-term Efficacy and Safety of Sitagliptin in Elderly Patients with Type 2 Diabetes Mellitus.

    PubMed

    Tada, Yuko; Kanazawa, Ippei; Notsu, Masakazu; Tanaka, Ken-Ichiro; Kiyohara, Nobuaki; Sasaki, Motofumi; Sugimoto, Toshitsugu

    2016-01-01

    Objective We herein conducted a retrospective study to evaluate the long-term efficacy and safety of sitagliptin treatment in elderly patients with type 2 diabetes mellitus. Methods We analyzed the changes in glycemic control in 112 Japanese type 2 diabetes patients over 65 years of age treated with 50 mg/day sitagliptin. Hemoglobin A1c (HbA1c) levels, liver and kidney functions, and usage of hypoglycemic agents were recorded for 24 months. Results HbA1c levels were significantly decreased, and the significance of HbA1c reduction was maintained during the observation period [from 7.7±1.1% to 7.2±0.7% (p<0.001) at the end of observational period]. The %change in HbA1c levels was significantly and negatively correlated with the baseline HbA1c levels (r=-0.51, p<0.001), but not with age, duration of diabetes, or the estimated glomerular filtration rate (eGFR). No patient experienced severe hypoglycemia episodes, and aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and the eGFR remained unchanged. The dose of sulfonylurea was finally decreased in 72% of patients treated with sulfonylurea. Conclusion Sitagliptin treatment continually decreases the HbA1c level for 24 months and is useful to reduce the dose of sulfonylurea in elderly patients with type 2 diabetes.

  13. Intestinal epithelial cell surface glycosylation in mice. I. Effect of high-protein diet.

    PubMed

    Gupta, R; Jaswal, V M; Meenu Mahmood, A

    1992-01-01

    The effects of variation in dietary protein content have been investigated on brush border glycosylation and enzyme activities in mice small intestine. The comparison of different parameters was made between the mice fed 30% (high protein, HP) and 18% protein (pair-fed, PF, and ad libitum-fed) for 21 days. The activities of brush border sucrase, lactase, p-nitrophenyl (PNP)-beta-D-glucosidase and PNP-beta-D-galactosidase were reduced in the HP diet-fed mice compared to PF and ad libitum-fed controls. Alkaline phosphatase and leucine amino-peptidase activities were significantly enhanced while gamma-glutamyl transpeptidase activity was unaltered under these conditions. Total hexoses and sialic acid content in the brush borders were reduced significantly in the test group compared to the controls while hexosamine and fucose contents remained essentially similar in different groups. The results on the binding of wheat germ agglutinin and Ulex europaeus agglutininI to microvillus membranes corroborated the chemical analysis data on sialic acid and fucose contents of the membranes. Peanut agglutinin binding was enhanced in mice from the HP group. Incorporation of (14C)-mannose into membranes was significantly less in HP diet-fed mice. These results indicate that the feeding of HP diet to mice brings about marked alterations in small intestinal epithelial cell surface glycosylation and enzyme functions.

  14. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics.

    PubMed

    Wilmes, Anja; Bielow, Chris; Ranninger, Christina; Bellwon, Patricia; Aschauer, Lydia; Limonciel, Alice; Chassaigne, Hubert; Kristl, Theresa; Aiche, Stephan; Huber, Christian G; Guillou, Claude; Hewitt, Philipp; Leonard, Martin O; Dekant, Wolfgang; Bois, Frederic; Jennings, Paul

    2015-12-25

    Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to biokinetics to identify cell stress response pathways induced by cisplatin. The human renal proximal tubular cell line RPTEC/TERT1 was treated with sub-cytotoxic concentrations of cisplatin (0.5 and 2 μM) in a daily repeat dose treating regime for up to 14 days. Biokinetic analysis showed that cisplatin was taken up from the basolateral compartment, transported to the apical compartment, and accumulated in cells over time. This is in line with basolateral uptake of cisplatin via organic cation transporter 2 and bioactivation via gamma-glutamyl transpeptidase located on the apical side of proximal tubular cells. Cisplatin affected several pathways including, p53 signalling, Nrf2 mediated oxidative stress response, mitochondrial processes, mTOR and AMPK signalling. In addition, we identified novel pathways changed by cisplatin, including eIF2 signalling, actin nucleation via the ARP/WASP complex and regulation of cell polarization. In conclusion, using an integrated omic approach together with biokinetics we have identified both novel and established mechanisms of cisplatin toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.

    PubMed

    Billones, Junie B; Carrillo, Maria Constancia O; Organo, Voltaire G; Macalino, Stephani Joy Y; Sy, Jamie Bernadette A; Emnacen, Inno A; Clavio, Nina Abigail B; Concepcion, Gisela P

    2016-01-01

    Mycobacterium tuberculosis (Mtb) the main causative agent of tuberculosis, is the main reason why this disease continues to be a global public health threat. It is therefore imperative to find a novel antitubercular drug target that is unique to the structural machinery or is essential to the growth and survival of the bacterium. One such target is the enzyme l,d-transpeptidase 2, also known as LdtMt2, a protein primarily responsible for the catalysis of 3→3 cross-linkages that make up the mycolyl-arabinogalactan-peptidoglycan complex of Mtb. In this study, structure-based pharmacophore screening, molecular docking, and in silico toxicity evaluations were employed in screening compounds from a database of synthetic compounds. Out of the 4.5 million database compounds, 18 structures were identified as high-scoring, high-binding hits with very satisfactory absorption, distribution, metabolism, excretion, and toxicity properties. Two out of the 18 compounds were further subjected to in vitro bioactivity assays, with one exhibiting a good inhibitory activity against the Mtb H37Ra strain.

  16. Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity

    PubMed Central

    Lee, Eun-Young; Lee, Hyun-Cheol; Kim, Hyun-Kwan; Jang, Song Yee; Park, Seong-Jun; Kim, Yong-Hoon; Kim, Jong Hwan; Hwang, Jungwon; Kim, Jae-Hoon; Kim, Tae-Hwan; Arif, Abul; Kim, Seon-Young; Choi, Young-Ki; Lee, Cheolju; Lee, Chul-Ho; Jung, Jae U; Fox, Paul L; Kim, Sunghoon; Lee, Jong-Soo; Kim, Myung Hee

    2016-01-01

    The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs+/−) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection. PMID:27595231

  17. Serum gamma-glutamyltransferase is inversely associated with dietary total and coffee-derived polyphenol intakes in apparently healthy Japanese men.

    PubMed

    Taguchi, Chie; Kishimoto, Yoshimi; Kondo, Kazuo; Tohyama, Kazushige; Goda, Toshinao

    2017-10-07

    Serum γ-glutamyltransferase (GGT) has been proposed as a marker of oxidative stress. Here, we examined the association between serum GGT and the dietary intake of polyphenols, which have antioxidant properties. A cross-sectional survey including 7960 apparently healthy Japanese men (aged 22-86 years) who participated in health checkups was conducted in Shizuoka, Japan. We analyzed these subjects' clinical serum parameters and lifestyle factors, including dietary polyphenol intake, which was evaluated by a self-administered questionnaire and by matching the subjects' food consumption data with our original polyphenol content database. The average intake of polyphenols was 1157 ± 471 mg/day, and green tea was the largest source of polyphenols at 40%, followed by coffee at 36%. Dividing the population according to quintiles of total polyphenol intake, the difference in polyphenol intake from coffee between the groups was much greater than the difference in polyphenol intake from green tea. The analysis of the association between polyphenol intake and biological parameters showed a significant negative association between polyphenol intake and the levels of systolic and diastolic blood pressure (SBP and DBP), GGT, and alanine aminotransferase (ALT) after adjusting for age, smoking habit, energy intake and alcohol intake. The GGT levels were inversely associated with the polyphenol intake from coffee, but not with that from green tea. Multivariable linear regression analyses demonstrated that the subjects' GGT levels were negatively and independently associated with their polyphenol intake. The intake of total polyphenol including coffee as a major contributor is inversely associated with the serum GGT concentration in Japanese males.

  18. Altered glutamyl-aminopeptidase activity and expression in renal neoplasms

    PubMed Central

    2014-01-01

    Background Advances in the knowledge of renal neoplasms have demonstrated the implication of several proteases in their genesis, growth and dissemination. Glutamyl-aminopeptidase (GAP) (EC. 3.4.11.7) is a zinc metallopeptidase with angiotensinase activity highly expressed in kidney tissues and its expression and activity have been associated wtih tumour development. Methods In this prospective study, GAP spectrofluorometric activity and immunohistochemical expression were analysed in clear-cell (CCRCC), papillary (PRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytoma (RO). Data obtained in tumour tissue were compared with those from the surrounding uninvolved kidney tissue. In CCRCC, classic pathological parameters such as grade, stage and tumour size were stratified following GAP data and analyzed for 5-year survival. Results GAP activity in both the membrane-bound and soluble fractions was sharply decreased and its immunohistochemical expression showed mild staining in the four histological types of renal tumours. Soluble and membrane-bound GAP activities correlated with tumour grade and size in CCRCCs. Conclusions This study suggests a role for GAP in the neoplastic development of renal tumours and provides additional data for considering the activity and expression of this enzyme of interest in the diagnosis and prognosis of renal neoplasms. PMID:24885240

  19. Effects of lifestyle changes including specific dietary intervention and physical activity in the management of patients with chronic hepatitis C – a randomized trial

    PubMed Central

    2013-01-01

    Background In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis. Methods Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m2. We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed. Results After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (−5.02 ± 3.43 kg vs. −4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1-year, however, weight loss was similar in both groups (−3.9 ± 3.3 kg vs. −3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p

  20. Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study

    PubMed Central

    2012-01-01

    Background Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. Methods We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Results Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Conclusions Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted. PMID:23075166

  1. Elongation of the Poly-γ-glutamate Tail of F420 Requires Both Domains of the F420:γ-Glutamyl Ligase (FbiB) of Mycobacterium tuberculosis*

    PubMed Central

    Bashiri, Ghader; Rehan, Aisyah M.; Sreebhavan, Sreevalsan; Baker, Heather M.; Baker, Edward N.; Squire, Christopher J.

    2016-01-01

    Cofactor F420 is an electron carrier with a major role in the oxidoreductive reactions of Mycobacterium tuberculosis, the causative agent of tuberculosis. A γ-glutamyl ligase catalyzes the final steps of the F420 biosynthesis pathway by successive additions of l-glutamate residues to F420-0, producing a poly-γ-glutamate tail. The enzyme responsible for this reaction in archaea (CofE) comprises a single domain and produces F420-2 as the major species. The homologous M. tuberculosis enzyme, FbiB, is a two-domain protein and produces F420 with predominantly 5–7 l-glutamate residues in the poly-γ-glutamate tail. The N-terminal domain of FbiB is homologous to CofE with an annotated γ-glutamyl ligase activity, whereas the C-terminal domain has sequence similarity to an FMN-dependent family of nitroreductase enzymes. Here we demonstrate that full-length FbiB adds multiple l-glutamate residues to F420-0 in vitro to produce F420-5 after 24 h; communication between the two domains is critical for full γ-glutamyl ligase activity. We also present crystal structures of the C-terminal domain of FbiB in apo-, F420-0-, and FMN-bound states, displaying distinct sites for F420-0 and FMN ligands that partially overlap. Finally, we discuss the features of a full-length structural model produced by small angle x-ray scattering and its implications for the role of N- and C-terminal domains in catalysis. PMID:26861878

  2. Regulation of a glutamyl-tRNA synthetase by the heme status

    PubMed Central

    Levicán, Gloria; Katz, Assaf; de Armas, Merly; Núñez, Harold; Orellana, Omar

    2007-01-01

    Glutamyl-tRNA (Glu-tRNA), formed by Glu-tRNA synthetase (GluRS), is a substrate for protein biosynthesis and tetrapyrrole formation by the C5 pathway. In this route Glu-tRNA is transformed to δ-aminolevulinic acid, the universal precursor of tetrapyrroles (e.g., heme and chlorophyll) by the action of Glu-tRNA reductase (GluTR) and glutamate semialdehyde aminotransferase. GluTR is a target of feedback regulation by heme. In Acidithiobacillus ferrooxidans, an acidophilic bacterium that expresses two GluRSs (GluRS1 and GluRS2) with different tRNA specificity, the intracellular heme level varies depending on growth conditions. Under high heme requirement for respiration increased levels of GluRS and GluTR are observed. Strikingly, when intracellular heme is in excess, the cells respond by a dramatic decrease of GluRS activity and the level of GluTR. The recombinant GluRS1 enzyme is inhibited in vitro by hemin, but NADPH restores its activity. These results suggest that GluRS plays a major role in regulating the cellular level of heme. PMID:17360620

  3. A comparative study of endoscopic ultrasonography versus endoscopic retrograde cholangiopancreatography in children with chronic liver disease.

    PubMed

    El-Karaksy, Hanaa M; El-Koofy, Nehal M; Okasha, Hussein; Kamal, Naglaa M; Naga, Mazen

    2008-09-01

    Endoscopic ultrasonography (EUS) is a less invasive modality and may be equal or superior to endoscopic retrograde cholangiopancreatography (ERCP) in visualizing the biliary tree. Its role and feasibility in children need to be accurately defined. This study aimed at evaluation of EUS in assessment of children with chronic liver disease (CLD) in comparison with ERCP. The present study was carried out between September 2004 and February 2006 on 40 children suffering from CLD. Patients were selected from the Pediatric Hepatology Unit, Cairo University Children's Hospital, Egypt. They were included if they had: sonographic (n = 8) or histopathological evidence of biliary pathology (n = 2); autoimmune hepatitis with high gamma glutammyl transpeptidase (GGT) levels and/or not responding to immunosuppressive therapy (n = 15); cryptogenic CLD (n = 13); neonatal cholestasis with relapsing or persistent course (n = 2). They all underwent EUS and ERCP. Three of six cases with intrahepatic biliary radicle dilatation had Caroli's disease by EUS and ERCP; and the other 3 had sclerosing cholangitis. EUS was equal to ERCP in diagnosis of biliary pathology. However, one false positive case was described to have dilatation and tortuosity of the pancreatic duct by EUS as compared to ERCP. EUS could detect early pancreatitis in 5 cases. One case with cryptogenic liver disease proved to have sclerosing cholangitis by both EUS and ERCP. EUS is an important diagnostic tool for biliary pathology and pancreatitis in children with pancreatico-biliary pathology. ERCP should be reserved for therapeutic purposes.

  4. The Effect of Freeze-Drying on the Nutrient, Polyphenol, and Oxidant Levels of Breast Milk.

    PubMed

    Cortez, Mariela Valentina; Soria, Elio Andrés

    2016-12-01

    Human milk banks need to extend the suitability of milk for breastfeeding, and for this technological advances are required. Our aim was to establish the capacity of freeze-drying to conserve milk properties without further oxidative deterioration. One hundred sixteen healthy women participated from the city of Cordoba (Argentina). Proteins, glucose, triglycerides, polyphenols, and markers (nitrites, superoxide anion, hydroperoxides, lipoperoxides, and γ-glutamyl transpeptidase) were measured in their fresh milk. Samples were then separated for three treatments as follows: freezing and conservation for 6 months at -80°C (F: positive control); freeze-drying for 24 hours at ≤-70°C and ≤1.33 Pa and conservation for 6 months at 4°C (FD: treatment of interest); and freeze-drying for 24 hours at ≤-70°C and ≤1.33 Pa and conservation for 6 months at -80°C (FD+F). Next, analyses were repeated and compared by ANOVA and Tukey tests. Fresh milk showed these values per L as follows: proteins: 12.62 ± 2.51 g, glucose: 4.44 ± 0.25 g, triglycerides: 34.26 ± 0.59 g, polyphenols: 53.27 ± 8.67 mg, nitrites: 62.40 ± 19.09 mg, superoxide: 3,721.02 ± 198.80 OD, hydroperoxides: 7,343.76 ± 294.53 OD, lipoperoxides: 7,349.72 ± 398.72 OD, and γ-glutamyl transpeptidase: 4.66 ± 0.55 IU. Glucose was decreased after F treatment (p < 0.05), all variables were conserved by FD and were not improved by the FD + F combination. Freeze-drying achieved suitable conservation and may improve bank functioning, by protecting nutritional properties, polyphenol-related functionality, and oxidative integrity of human milk through a 1-day treatment with easy maintenance.

  5. Liquid chromatography-mass spectrometry (LC-MS): a powerful combination for selenium speciation in garlic (Allium sativum).

    PubMed

    Dumont, Emmie; Ogra, Yasumitsu; Vanhaecke, Frank; Suzuki, Kazuo T; Cornelis, Rita

    2006-03-01

    Liquid chromatography (LC) hyphenated with both elemental and molecular mass spectrometry has been used for Se speciation in Se-enriched garlic. Different species were separated by ion-pair liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS) after hot-water extraction. They were identified by on-line reversed-phase liquid chromatography-electrospray ionization tandem mass spectrometry (RPLC-ESI-MS-MS). Se-methionine and Se-methylselenocysteine were determined by monitoring their product ions. Another compound, gamma-glutamyl-Se-methylselenocysteine, shown to be the most abundant form of Se in the garlic, was determined without any additional sample pre-treatment after extraction and without the need for a synthesized standard. Product ions for this dipeptide were detected by LC-ESI-MS-MS for three isotopes of Se-78 Se, 80Se: and 82Se. The method was extended to the species extracted during in-vitro gastrointestinal digestion. Because both Se-methylselenocysteine and gamma-glutamyl-Se-methylselenocysteine have anticarcinogenic properties, their extractability and stability during human digestion are very important. Garlic was also treated with saliva, to enable detection and analysis of species extracted during mastication. Detailed information on the extractability of selenium species by both simulated gastric and intestinal fluid are given, and variation of the distribution of Se among the different species with time is discussed. Although the main species in garlic is the dipeptide gamma-glutamyl-Se-methylselenocysteine, Se-methylselenocysteine is the main compound present in the extracts after treatment with gastrointestinal fluids. Two more, so far unknown compounds were observed in the chromatogram. The extracted species and their transformations were analysed by combining LC-ICP-MS and LC-ESI-MS-MS. In both the simulated gastric and intestinal digests, Se-methionine, Se-methylselenocysteine, and gamma-glutamyl

  6. Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis.

    PubMed

    Liberato, Isabella Ramos de Oliveira; Lopes, Edmundo Pessoa de Almeida; Cavalcante, Maria Alina Gomes de Mattos; Pinto, Tiago Costa; Moura, Izolda Fernades; Loureiro Júnior, Luiz

    2012-01-01

    The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before

  7. Influence of esterified-glucomannan on performance and organ morphology, serum biochemistry and haematology in broilers exposed to individual and combined mycotoxicosis (aflatoxin, ochratoxin and T-2 toxin).

    PubMed

    Raju, M V; Devegowda, G

    2000-12-01

    1. A study was conducted to evaluate the individual and combined effects of aflatoxin B1 (AF), ochratoxin A (OA) and T-2 toxin (T-2) on performance, organ morphology serum biochemistry and haematology of broiler chickens and the efficacy of esterified-glucomannan (E-GM), a cell wall derivative of Saccharomyces cerevisiae1026 in their counteraction. 2. Two dietary inclusion rates of AF (0 and 0.3 mg/kg), OA (0 and 2 mg/kg), T-2 (0 and 3 mg/kg) and E-GM (0 and 1 g/kg) were tested in a 2 x 2 x 2 x 2 factorial manner on a total of 960 broiler chickens from 1 to 35 d of age in an open sided deep litter pen house. 3. Body weight and food intake were depressed by all the mycotoxins, OA being the most toxic during early life. 4. Weights of kidney and adrenals were increased by AF and OA. Liver weight was increased by AF (17.8%), while OA increased gizzard weight (14.6%) and reduced bone ash content (8.1%). T-2 toxin showed no effect on these variables. 5. Serum cholesterol content was decreased and activity of serum gamma glutamyl transferase (GGT) was increased by AF and OA while serum protein content was decreased by AF. These effects were more pronounced at 21 d than at 35 d of age. Inconsistent responses were seen in the other variables: blood urea nitrogen (BUN) content, activities of serum alanine amino transferase and aspertate amino transferase. Blood haemoglobin content was depressed by AF and T-2, whereas blood coagulation time was prolonged by OA. 6. Significant interactions were observed between any 2 toxins for their additive effects on body weight, food intake, bone ash content and serum GGT activity at 21 d. Conversely, antagonistic interactions were observed among any 2 of the toxins for their effects on variables such as serum protein and serum cholesterol content. Simultaneous feeding of all 3 mycotoxins did not show increased toxicity above that seen with any 2. 7. Esterified-glucomannan increased body weight (2.26%) and food intake (1.6%), decreased

  8. Evaluation of inflammation during fixed orthodontic treatment.

    PubMed

    Bilgic, Fundagul; Akinci Sozer, Ozlem; Ozcan, Oguzhan; Gurpinar, Ahmet Burak; Yilmaz, Hakki; Ay, Yazgi

    2016-11-01

    The aim of this study was to assess effects of fixed orthodontic therapy on high-sensitivity C-reactive protein (hs-CRP) level, CBC parameters and levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), urea, creatinine, sodium (Na), potassium (K), calcium (Ca), total protein (TP), and albumin (Alb). Blood samples (7ml) were drawn at baseline, on days 1 and 7, and three months after placement of braces in the study group, while only one blood sample was drawn at baseline in the control group. Serum hs-CRP levels were measured by nephelometric method. Friedman two-way variance analysis was used to assess values with skewed distribution obtained at baseline, on days 1 and 7, in the third month. Wilcoxon rank sign test was performed if median values were unequal. During measurement periods, there were significant increases in hs-CRP level, WBC count and neutrophil count while a significant decrease in Na level (p<0.05). K level was significantly decreased on the day 1. No significant differences were detected in other biochemical parameters evaluated. Elevation in serum hs-CRP levels and neutrophil: lymphocyte ratio within first 3 months indicates that a systemic immune response develops against therapy in patients undergoing fixed orthodontic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Morbidity-mortality and performance evaluation of Brahman calves from in vitro embryo production

    PubMed Central

    2011-01-01

    Background The use of bovine in vitro embryo production (IVP) increases the reproductive potential of genetically superior cows, enabling a larger scale of embryo production when compared with other biotechnologies. However, deleterious effects such as abnormal fetal growth, longer gestation period, increased birth weight, abortion, preterm birth and higher rates of neonatal mortality have been attributed to IVP. The aim of this study was to compare the influence of in vitro embryo production and artificial insemination (AI) on gestation length, complications with birth, birth weight, method of feeding colostrum, passive transfer of immunity, morbidity-mortality, and performance in Brahman calves. Results Whilst gestation length and birth weight were significantly increased in IVP-derived calves, no difference in weaning weight was observed between groups. The passive transfer of immunity (PT), was assessed in IVP (n = 80) and AI (n = 20) groups 24 hours after birth by determination of gamma-glutamyl transferase (GGT) and gammaglobulin activity as well as by quantification of the concentration of total protein in serum. No differences in passive transfer or incidences of dystocia and diseases at weaning were observed between groups. Birth weight, method of feeding colostrum and dystocia were not correlated with PT in either group. Conclusions In this study, in vitro embryo production did not affect the health status, development, or passive transfer of immunity in Brahman calves. PMID:22136315

  10. Hepatoprotective Role of Wheatgrass on Alcohol and ΔPUFA-Induced Oxidative Stress in Rats.

    PubMed

    Durairaj, Varalakshmi; Shakya, Garima; Rajagopalan, Rukkumani

    2015-06-01

    Alcohol abuse is recognized as the most common cause for the development of various abnormalities including liver disease. Excessive free radicals are generated during the metabolism of ethanol. The ingestion of alcohol along with polyunsaturated fatty acid (PUFA) aggravates the production of free radicals and enhances the oxidative stress. Medicinal plants contain active phytocomponents, which are the principal healthcare resources. We aimed to analyze the effect of wheatgrass extract on alcohol and thermally oxidized PUFA (ΔPUFA) induced oxidative stress in male albino Wistar rats. The levels of marker enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), lipid peroxidative markers; thiobarbutric acid reactive substances (TBARS) and lipid hydroperoxides (LH), the levels of enzymatic (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]) and nonenzymatic (reduced glutathione [GSH], vitamin E, vitamin C) antioxidants were analyzed in liver to evaluate the effects of wheatgrass. The levels of TBARS and LH were significantly (p ≤ .05) increased in alcohol + ΔPUFA group, which were found to be reduced on treatment with wheatgrass. The levels of both enzymatic and nonenzymatic antioxidants were significantly (p ≤ .05) decreased in alcohol + ΔPUFA group, which were found to be restored on treatment with wheatgrass. From the results obtained, we conclude that wheatgrass protects the liver against alcohol and ΔPUFA induced oxidative stress.

  11. Hepatoprotective and nephroprotective effects of sardinelle (Sardinella aurita) protein hydrolysate against ethanol-induced oxidative stress in rats.

    PubMed

    Kamoun, Zeineb; Kamoun, Alya Sellami; Bougatef, Ali; Kharrat, Rim Marrakchi; Youssfi, Houssem; Boudawara, Tahia; Chakroun, Mouna; Nasri, Moncef; Zeghal, Najiba

    2017-01-01

    Ethanol consumption-induced oxidative stress that is a major etiological factor has been proven to play important roles in organs' injury. In the present study, we investigated the protective effect of fish protein hydrolysate prepared from the heads and viscera of sardinelle (Sardinella aurita) (SPH) against the toxicity of ethanol on the liver and kidney of adult male rats. Animals were divided into four groups of six animals each: group C served as control, group Eth received 30 % ethanol solution at the dose of 3 g/kg body weight, group SPH received only 7.27 mg of SPH/kg body weight, and group Eth-SPH received ethanol and SPH simultaneously at the doses of 30 % and 7.27 mg/kg body weight, respectively. All groups were treated by gavage way for 15 days. Ethanol treatment decreased the defense enzymatic system including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), which increased after the co-administration of SPH. Malondialdehyde (MDA) and toxicity biomarker levels such as aspartate transaminase (AST) and alanine transaminase (ALT) and alcaline phosphatase (ALP) and gamma-glutamyl transaminase (GGT) activities were enhanced after chronic ethanol treatment and reduced by co-treatment with SPH. The histological examination of the liver and kidney confirmed biochemical changes in ethanol-treated rats and demonstrated the protective role of SPH.

  12. Elevated fasting glucose and albuminuria may be a marker for all-cause mortality in Indigenous adults in North Queensland - a follow up study, 1998-2006.

    PubMed

    Li, Ming; McDermott, Robyn

    2017-04-01

    To document risk factors of all-cause mortality in a cohort of indigenous Australians from 23 communities of North Queensland during 1998-2006. Among 2787 indigenous adults, baseline weight, waist circumference, blood pressure, fasting glucose, lipids, gamma-glutamyl transferase, urine albumin creatinine ratio, smoking, alcohol intake and physical activity were measured in 1998-2000. Deaths were ascertained from State Registry of Deaths, hospitalization and clinical records till 2006. Mortality risk factors were assessed using a Cox proportional-hazards model. The standardized all-cause mortality rate was 23.2/1000 person-years (95% CI 20.3-26.3/1000 pys). After adjusting for age, sex, and ethnicity, baseline plasm fasting glucose >=5.5mmol/L was associated with a 50% increased risk of death (HR 1.5, 95% CI 1.2-2.0). Albuminuria was associated with all-cause mortality with a hazards ratio of 1.4 for microalbuminuria (95% CI 1.0-1.9) and 2.6 (95% CI 1.8-3.7) for macroalbuminuria. Gamma-glutamyl transferase >=50IU was associated with an increased risk of all-cause mortality by 40% (95% CI 1.04-1.8). Fasting glycaemia, albuminuria, and gamma-glutamyl transferase, may be a marker for all-cause mortality within this cohort. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Localization and characterization of γ-glutamyl cyclotransferase in cancer cells.

    PubMed

    Azumi, Kaoru; Ikeda, Youhei; Takeuchi, Tomoharu; Nomura, Tsuyoshi; Sabau, Sorin V; Hamada, Jun-Ichi; Okada, Futoshi; Hosokawa, Masuo; Yokosawa, Hideyoshi

    2009-01-01

    Using differential display analysis, we have identified a novel rat gene whose expression is increased during tumor progression in rat mammary carcinoma cell lines. This gene is an ortholog of the human chromosome 7 open reading frame 24 gene (C7orf24) and encodes a protein of 188 amino acids with no recognized protein domains. C7orf24 has been identified as γ-glutamyl cyclotransferase (GGCT), an important enzyme functioning in glutathione homeostasis. Our Northern and Western blot analyses revealed that the GGCT gene is expressed in various normal human and tumor tissues, as well as in cancer cell lines. Among the tumor tissues tested, lung tumor tissue expressed GGCT mRNA more strongly than normal lung tissue. The GGCT protein was found to be localized in the cytoplasmic region of cultured cells, where it forms a homodimer. Analysis of various deletion mutants of the GGCT protein revealed that the region containing amino acid residues 61-120 of the protein is required for its cytoplasmic localization. The comparison of the soft agar colony formation of HBL-100 cells stably expressing GGCT with that of control HBL-100 cells revealed that GGCT does not promote colony formation, suggesting that the role it plays in lung cancer cells is not related to tumorigenesis.

  14. Changes in white cell estimates and plasma chemistry measurements following oral or external dosing of double-crested cormorants, Phalacocorax auritus, with artificially weathered MC252 oil.

    PubMed

    Dean, Karen M; Bursian, Steven J; Cacela, Dave; Carney, Michael W; Cunningham, Fred L; Dorr, Brian; Hanson-Dorr, Katie C; Healy, Kate A; Horak, Katherine E; Link, Jane E; Lipton, Ian; McFadden, Andrew K; McKernan, Moira A; Harr, Kendal E

    2017-12-01

    Scoping studies were designed whereby double-crested cormorants (Phalacocorax auritus) were dosed with artificially weathered Deepwater Horizon (DWH) oil either daily through oil injected feeder fish, or by application of oil directly to feathers every three days. Preening results in oil ingestion, and may be an effective means of orally dosing birds with toxicant to improve our understanding of the full range of physiological effects of oral oil ingestion on birds. Blood samples collected every 5-6 days were analyzed for a number of clinical endpoints including white blood cell (WBC) estimates and differential cell counts. Plasma biochemical evaluations were performed for changes associated with oil toxicity. Oral dosing and application of oil to feathers resulted in clinical signs and statistically significant changes in a number of biochemical endpoints consistent with petroleum exposure. In orally dosed birds there were statistically significant decreases in aspartate amino transferase (AST) and gamma glutamyl transferase (GGT) activities, calcium, chloride, cholesterol, glucose, and total protein concentrations, and increases in plasma urea, uric acid, and phosphorus concentrations. Plasma electrophoresis endpoints (pre-albumin, albumin, alpha-2 globulin, beta globulin, and gamma globulin concentrations and albumin: globulin ratios) were decreased in orally dosed birds. Birds with external oil had increases in urea, creatinine, uric acid, creatine kinase (CK), glutamate dehydrogenase (GLDH), phosphorus, calcium, chloride, potassium, albumin, alpha-1 globulin and alpha-2 globulin. Decreases were observed in AST, beta globulin and glucose. WBC also differed between treatments; however, this was in part driven by monocytosis present in the externally oiled birds prior to oil treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. [Risk factors associated with non-alcoholic fatty liver disease: a case-control study].

    PubMed

    Caballería, Llorenç; Arteaga, Ingrid; Pera, Guillem; Rodríguez, Lluís; Alumà, Alba; Auladell, Maria Antònia; Torán, Pere

    2013-09-21

    To establish the factors associated with the presence of non-alcoholic fatty liver disease (NAFLD) and evaluate the influence of each component constituting the metabolic syndrome (MS) and the risk of developing NAFLD. We performed a multicenter, population-based, observational, analytical study of cases and controls. A case was defined as any patient fulfilling the inclusion criteria and presenting NAFLD by abdominal echography for any reason. A control was randomly selected for each case, from the same health center and of the same age and sex. All the cases underwent anamnesis, physical examination, complete biochemical analyses and determination of MS according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. All the controls also underwent an abdominal echography. We included 327 cases and 377 controls with a mean age of 56 ± 12 years for the cases and of 55 ± 13 years for the controls (range: 17 and 80 years); 52.0% of the cases were males and 49.1% of males were controls. The risk factors associated with NAFLD were obesity (odds ratio [OR] 3.82, 95% confidence interval [95% CI] 2.19-6.66), MS (OR 1.73, 95% CI 1.09-2.75), insulin resistance (OR 3.65, 95% CI 2.18-6.12), and an increase in alanine aminotransferase (ALT) (OR 4.72, 95% CI 2.58-8.61) and gamma glutamyl transferase values (GGT) (OR 1.95, 95% CI 1.14-3.34). The components of the MS best predicting NAFLD were hyperglycemia (OR 1.65, 95% CI1.06-2.56) and triglyceride values (OR 1.75, 95% CI1.13-2.72). The independent variables associated with NAFLD were obesity, insulin resistance and elevated ALT and GGT. The components of MS best predicting NAFLD were hyperglycemia and an increase in triglyceride values. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  16. [Effect of altitude chronic hypoxia on liver enzymes and its correlation with ACE/ACE2 in yak and migrated cattle].

    PubMed

    Liu, Feng-yun; Hu, Lin; Li, Yu-xian; Liu, Shi-ming; Tang, Yong-ping; Qi, Sheng-gui; Yang, Lei; Wu, Tian-yi

    2015-05-01

    To investigate the difference of liver enzyme levels and its correlation with serum ACE/ACE2 among yak and cattle on Qinghai-Tibetan plateau, and to further explore the biochemical mechanism of their liver of altitude adaptation. The serum samples of yak were collected at 3,000 m, 3,500 m, 4,000 m and 4,300 m respectively, meanwhile the serum samples of migrated cattle on plateau (2,500 m) and lowland cattle (1,300 m) were also collected. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), serum lipase (LPS), angiotensin converting enzyme(ACE), angiotensin converting enzyme-2 (ACE2) in serum were measured by using fully automatic blood biochemcal analyzer. We analysed the differences of the above enzymes and its correlation with ACE/ACE2. We used one way analysis of variance (ANOVA). The levels of ALT in 4,000 m group and 4,300 m group of yak increased significantly compared with other groups, there were no statistically significant differences in AST, CHE, GGT, ACE/ACE2 levels of yaks at different altitudes. As compared to lowland cattle, the serum levels of AST and CHE were increased, the level of LPS and ACE was decreased significantly, respectively, and especially, the ratio of ACE/ACE2 of migranted cattle reduced nearly two times. The levels of LPS were significantly correlated to the ratio of ACE/ACE2 in yak (r = 0.357, P < 0.01), and a high correlation between ALP and ACE/ACE2 in lowland cattle( r = 0.418, P < 0.05), But the biggest contribution rate of the ratio of ACE/ACE2 was only 17.5% for the changes of the levels of liver enzyme. The results indicated that with the altitude increased did not significantly influence the changes of liver enzymes' activities in mountainous yaks but not in cattle. However, all above these changes weren't actually correlated to the ratio of ACE/ACE2.

  17. Liver Biomarkers and Lipid Profiles in Mexican and Mexican-American 10- to 14-Year-Old Adolescents at Risk for Type 2 Diabetes

    PubMed Central

    Fernández-Gaxiola, Ana Cecilia; Fulda, Kimberly G.; Martínez-Carrillo, Beatriz E.; Franks, Susan F.; Fernando, Shane

    2017-01-01

    Liver enzymes alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) are markers for type 2 diabetes mellitus (T2DM); alkaline phosphatase is a marker of liver disease. Mexican-American adolescents are disproportionately affected by T2DM, while in Mexico its prevalence is emerging. We assessed liver biomarkers and lipid profiles among Mexican and Mexican-American adolescents 10–14 years old with high/low risk of T2DM through a cross-sectional, descriptive study (Texas n = 144; Mexico n = 149). We included family medical histories, anthropometry, and blood pressure. Obesity was present in one-third of subjects in both sites. ALT (UL) was higher (p < 0.001) in high-risk adolescents (23.5 ± 19.5 versus 17.2 ± 13.4 for males, 19.7 ± 11.6 versus 15.1 ± 5.5 for females), in Toluca and in Texas (26.0 ± 14.7 versus 20.0 ± 13.2 for males, 18.2 ± 13.4 versus 14.6 ± 10.1 for females), as well as GGT (UL) (p < 0.001) (18.7 ± 11.1 versus 12.4 ± 2.3 for males, 13.6 ± 5.8 versus 11.5 ± 3.9 for Mexican females; 21.0 ± 6.8 versus 15.4 ± 5.5 for males, 14.3 ± 5.0 versus 13.8 ± 5.3 for females in Texas). We found no differences by sex or BMI. Total cholesterol and HDL were higher among Mexican-Americans (p < 0.001). In conclusion, multiple risk factors were present in the sample. We found differences by gender and between high and low risk for T2DM adolescents in all liver enzymes in both sites. PMID:28929119

  18. Phosphorus amendment reduces hepatic and renal oxidative stress in mallards ingesting lead-contaminated sediments

    USGS Publications Warehouse

    Hoffman, D.J.; Heinz, G.H.; Audet, D.J.

    2006-01-01

    Lead poisoning of waterfowl has been reported for decades in the Coeur d'Alene River Basin (CDARB) in Idaho as a result of the ingestion of lead-contaminated sediments. This study was conducted to determine whether the addition of phosphoric acid to CDARB sediments would reduce the bioavailability and toxicity of lead to the liver and kidney of mallards (Anas platyrhynchos). Mallards received diets containing 12% clean sediment (controls) or 12% sediment from three different CDARB sites containing 4520, 5390, or 6990 ug/g lead (dry weight) with or without phosphoric acid amendment. Liver and kidney lead concentrations were significantly higher in all CDARB treatment groups and ranged from geometric mean values of 18.2 (liver) and 28.7 (kidney) for the first 2 sites to 22.5 (liver) and 45.6 (kidney) ug/g (wet weight) for the third site. With amendments all liver lead concentrations were reduced 36 to 55%, and all kidney lead concentrations were lowered 54 to 73%. Unamended CDARB sediment from the third site resulted in the following hepatic effects: over 1.6-fold elevation of liver glutathione (reduced form; GSH) concentration, higher GSH S-transferase and oxidized glutathione (GSSG) reductase activities, and lower protein-bound thiols (PBSH) concentration. Renal effects included higher kidney GSH concentrations for all CDARB sites, with over 2.1-fold higher for the third site. Resulting kidney GSSG to GSH ratios were lower at two sites. At the third site, gamma-glutamyl transferase (GGT) activity was elevated, and lipid peroxidation as thiobarbituric acid-reactive substances (TBARS) was 1.7-fold greater. Amendment restored all hepatic variables as well as the renal variables TBARS and GGT so they did not differ from controls. Although amendments of phosphorus substantially reduced the bioavailability of lead and some of the adverse effects, lead concentrations in the tissues of mallards fed the amended sediments were still above those considered to be harmful to

  19. Efficacy of albendazole in combination with thymol against Echinococcus multilocularis protoscoleces and metacestodes.

    PubMed

    María, Albani Clara; Celina, Elissondo María

    2014-12-01

    The larval (metacestode) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a mainly hepatic disease characterized by continuous asexual proliferation of metacestodes by exogenous budding, resulting in the tumor-like, infiltrative growth of the parasite lesion. Current chemotherapeutical treatment of AE relies on the use of benzimidazoles, albendazole (ABZ) and mebendazole, but these drugs act parasitostatic rather than parasitocidal, and due to their low success rate they imply a lifelong application causing severe side effects. Thymol is one of the major components of the essential oils of Thymus and is a widely known anti-microbial agent. The aim of the present work was to compare the efficacy of albendazole (ABZ) and thymol separately or combined on E. multilocularis protoscoleces and metacestodes. For this purpose, microscopical examinations at different time points were carried out. Moreover the tegumentary enzyme gamma glutamyl transferase (GGT) was measured to quantify the damage in metacestodes. Even though treatments of in vitro cultured E. multilocularis protoscoleces or metacestodes with ABZ or/and thymol showed that the drugs have an adverse effect on parasite viability, the combination of the two compounds at the concentration of 10μg/ml showed the maximum anti-parasitic effect. Three days postincubation the first effects of the treatment were detected on protoscoleces and a marked reduction in viability (33%) was registered at day 18. Incubation of E. multilocularis metacestodes in the presence of ABZ 10μg/ml+thymol 10μg/ml during 10 days resulted in dramatic alterations such as strongly irregular and fissured surface and markedly disrupted vesicles. Scanning electron microscopy showed that protoscoleces as well as the germinal layer of E. multilocularis metacestodes were dramatically damaged following ABZ or/and thymol treatment. Also an important increase of tegumentary enzyme GGT was registered after 72h

  20. Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Beretta, Alberto; Accinni, Roberto; Dellanoce, Cinzia; Tonini, Annamaria; Cardot, Jean-Michel; Bussière, Anthony

    2016-06-01

    The antioxidant, anti-inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double-blind, placebo-controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3-month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty-five subjects (56.0 ± 11.6 years) were enrolled. The results showed a beneficial and statistically significant effect versus placebo of PM extract on liver function, with a decrease versus baseline in alanine aminotransferase (47%), aspartate aminotransferase (7%), gamma-glutamyl transpeptidase (15%) and glycemia (11%). The lipid profile modification was also positive with an increase versus baseline in HDL cholesterol (13%), and a decrease in LDL/HDL ratio (12%) and triglycerides (8%). The antioxidant action of PM translated into a decrease in oxidized glutathione, reduced/oxidized cysteine-glycine, oxidized cysteine (intracellular pro-oxidant) and neopterin (inflammation biomarker), was associated with an increase in reduced glutathione. These results are in favor of the use of a standardized extract of P. mume for the support of liver health and prevention of common metabolic and inflammation-based diseases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Polychlorinated biphenyl exposure and effects in transformer repair workers.

    PubMed Central

    Emmett, E A

    1985-01-01

    Fifty-five present and past transformer repair workers exposed to polychlorinated biphenyls (PCBs) and 56 unexposed comparison workers were evaluated in a clinical-epidemiologic study. The groups were similar in most demographic variables. Adipose tissue lipid and serum PCBs concentrations were higher in current exposed workers (geometric means adipose 2.1 ppm, serum 12.2 ppb). Concentrations in comparison (0.6 ppm and 4.6 ppb) and previously exposed (0.83 ppm and 5.9 ppb) workers were lower. Statistically significant differences in serum albumin and lactic dehydrogenase, but not in other liver function tests, were seen between the exposed and comparison groups; however, after adjustment for confounding variables, no correlations were observed between liver function tests and either adipose or serum PCBs concentrations. Statistically significant correlation both before and after adjustment for confounding variables were seen with adipose PCBs and 24-hr urinary 17-hydroxycorticosteroid excretion and with serum PCBs and serum gamma-glutamyl transpeptidase. Both associations could reflect microsomal enzyme induction among other possibilities. No differences were seen in fasting serum triglycerides, total cholesterol, LDL, HDL or VLDL cholesterol between the two exposure groups. A statistically significant correlation between serum PCBs and serum triglycerides, total cholesterol, and VLDL cholesterol was removed by adjusting for confounding variables. No correlation was seen between adipose PCBs concentrations and any serum lipid component. Partition phenomena could account for these findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2863134

  2. Oral administration of Saccharomyces boulardii alters duodenal morphology, enzymatic activity and cytokine production response in broiler chickens.

    PubMed

    Sun, Yajing; Rajput, Imran Rashid; Arain, Muhammad Asif; Li, Yanfei; Baloch, Dost Muhammad

    2017-08-01

    The present study evaluated the effects of Saccharomyces boulardii on duodenal digestive enzymes, morphology and cytokine induction response in broiler chicken. A total of 200 birds were allotted into two groups (n = 100) and each group divided into five replications (n = 20). The control group was fed basal diet in addition to antibiotic (virginiamycin 20 mg/kg), and treatment group received (1 × 10 8  colony-forming units/kg feed) S. boulardii in addition to basal diet lasting for 72 days. The results compared to control group revealed that adenosine triphosphatase, gamma glutamyl transpeptidase, lipase and trypsin activities were higher, while, no significant improvement was observed in amylase activities in the duodenum of the treatment group. Moreover, morphological findings showed that villus height, width and number of goblet cells markedly increased. Additionally, transmission electron microscopy visualized that villus height, width and structural condensation significantly increased in the treatment group. The immunohistological observations showed increased numbers of immunoglobulin A (IgA)-positive cells in the duodenum of the treatment group. Meanwhile, cytokine production levels of tumor necrosis factor-α, interleukin (IL)-10, transforming growth factor-β and secretory IgA markedly increased, and IL-6 statistically remained unchanged as compared to the control group. These findings illustrated that initial contact of S. boulardii to the duodenum has significant impact in improving enzymatic activity, intestinal morphology and cytokine response in broiler chicken. © 2016 Japanese Society of Animal Science.

  3. Hepatoprotective and toxicological studies of Salvia bucharica methanolic extract in rabbits.

    PubMed

    Ahmad, Mansoor; Muhammed, Shafi; Mehjabeen, -; Jahan, Noor

    2014-11-01

    Most of the species of genus Salvia are famous for having medicinal properties due to their chemical constituents. Salvia bucharica (Lamiacea) is found in Balochistan near Quetta in Hannaurak and Kalat. It is used in traditional system of medicine and claims to cure liver ailments. In current study crude methanolic extract (CME) of Salvia bucharica was obtained from the leaves and tested for hepatoprotective activity and possible toxicity in rabbits. Liver toxicity was induced in rabbits by administration of carbon tetra chloride (CCl4) and evaluated by biochemical tests and histopathology of tissues. In this study rabbits were divided in to 3 groups (5 rabbit in each group). Rabbits of group I (control) were administered only vehicle (0.9% sodium chloride) orally. Rabbits of group II were given CCl4 and group III were treated with CCl4 and S. bucharica CME orally. For hepatoprotective effect serum enzyme level and total protein level were calculated. Histopathology of liver sections of rabbits was also carried out to observe protective effect. Biochemical, hematological and histoptahological parameters were studied on rabbits for toxicological studies. S. bucharica CME showed significant liver protection with reduction in total bilirubin, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT). And decrease in Albumin and globulin. In toxicological studies, biochemical and histoptahological parameters showed no significant toxicity in liver, heart and kidneys. It is concluded that S. bucharica CME showed hepatoprotective effects with nontoxic profile.

  4. A Conformational Investigation of Propeptide Binding to the Integral Membrane Protein γ-Glutamyl Carboxylase Using Nanodisc Hydrogen Exchange Mass Spectrometry

    PubMed Central

    2015-01-01

    Gamma (γ)-glutamyl carboxylase (GGCX) is an integral membrane protein responsible for the post-translational catalytic conversion of select glutamic acid (Glu) residues to γ-carboxy glutamic acid (Gla) in vitamin K-dependent (VKD) proteins. Understanding the mechanism of carboxylation and the role of GGCX in the vitamin K cycle is of biological interest in the development of therapeutics for blood coagulation disorders. Historically, biophysical investigations and structural characterizations of GGCX have been limited due to complexities involving the availability of an appropriate model membrane system. In previous work, a hydrogen exchange mass spectrometry (HX MS) platform was developed to study the structural configuration of GGCX in a near-native nanodisc phospholipid environment. Here we have applied the nanodisc–HX MS approach to characterize specific domains of GGCX that exhibit structural rearrangements upon binding the high-affinity consensus propeptide (pCon; AVFLSREQANQVLQRRRR). pCon binding was shown to be specific for monomeric GGCX-nanodiscs and promoted enhanced structural stability to the nanodisc-integrated complex while maintaining catalytic activity in the presence of carboxylation co-substrates. Noteworthy modifications in HX of GGCX were prominently observed in GGCX peptides 491–507 and 395–401 upon pCon association, consistent with regions previously identified as sites for propeptide and glutamate binding. Several additional protein regions exhibited minor gains in solvent protection upon propeptide incorporation, providing evidence for a structural reorientation of the GGCX complex in association with VKD carboxylation. The results herein demonstrate that nanodisc–HX MS can be utilized to study molecular interactions of membrane-bound enzymes in the absence of a complete three-dimensional structure and to map dynamic rearrangements induced upon ligand binding. PMID:24512177

  5. Genome Analysis of F. nucleatum sub spp vincentii and Its Comparison With the Genome of F. nucleatum ATCC 25586

    PubMed Central

    Kapatral, Vinayak; Ivanova, Natalia; Anderson, Iain; Reznik, Gary; Bhattacharyya, Anamitra; Gardner, Warren L.; Mikhailova, Natalia; Lapidus, Alla; Larsen, Niels; D'Souza, Mark; Walunas, Theresa; Haselkorn, Robert; Overbeek, Ross; Kyrpides, Nikos

    2003-01-01

    We present the draft genome sequence and its analysis for Fusobacterium nucleatum sub spp. vincentii (FNV), and compare that genome with F. nucleatum ATCC 25586 (FN). A total of 441 FNV open reading frames (ORFs) with no orthologs in FN have been identified. Of these, 118 ORFs have no known function and are unique to FNV, whereas 323 ORFs have functional orthologs in other organisms. In addition to the excretion of butyrate, H2S and ammonia-like FN, FNV has the additional capability to excrete lactate and aminobutyrate. Unlike FN, FNV is likely to incorporate galactopyranose, galacturonate, and sialic acid into its O-antigen. It appears to transport ferrous iron by an anaerobic ferrous transporter. Genes for eukaryotic type serine/threonine kinase and phosphatase, transpeptidase E-transglycosylase Pbp1A are found in FNV but not in FN. Unique ABC transporters, cryptic phages, and three types of restriction-modification systems have been identified in FNV. ORFs for ethanolamine utilization, thermostable carboxypeptidase, γ glutamyl-transpeptidase, and deblocking aminopeptidases are absent from FNV. FNV, like FN, lacks the classical catalase-peroxidase system, but thioredoxin/glutaredoxin enzymes might alleviate oxidative stress. Genes for resistance to antibiotics such as acriflavin, bacitracin, bleomycin, daunorubicin, florfenicol, and other general multidrug resistance are present. These capabilities allow Fusobacteria to survive in a mixed culture in the mouth. PMID:12799352

  6. Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children.

    PubMed

    Xiong, Xianzhi; Liu, Junling; He, Weihong; Xia, Tao; He, Ping; Chen, Xuemin; Yang, Kedi; Wang, Aiguo

    2007-01-01

    Although a dose-effect relationship between water fluoride levels and damage to liver and kidney functions in animals has been reported, it was not demonstrated in humans. To evaluate the effects of drinking water fluoride levels on the liver and kidney functions in children with and without dental fluorosis, we identified 210 children who were divided into seven groups with 30 each based on different drinking water fluoride levels in the same residential area. We found that the fluoride levels in serum and urine of these children increased as the levels of drinking water fluoride increased. There were no significant differences in the levels of total protein (TP), albumin (ALB), aspartate transamine (AST), and alanine transamine (ALT) in serum among these groups. However, the activities of serum lactic dehydrogenase (LDH), urine N-acetyl-beta-glucosaminidase (NAG), and urine gamma-glutamyl transpeptidase (gamma-GT) in children with dental fluorosis and having water fluoride of 2.15-2.96 mg/L and in children having water fluoride of 3.15-5.69 mg/L regardless of dental fluorosis were significantly higher than children exposed to water fluoride of 0.61-0.87 mg/L in a dose-response manner. In contrast to children with dental fluorosis and having water fluoride of 2.15-2.96 and 3.10-5.69 mg/L, serum LDH activity of children without dental fluorosis but exposed to the same levels of water fluoride as those with dental fluorosis were also markedly lower, but the activities of NAG and gamma-GT in their urine were not. Therefore, our results suggest that drinking water fluoride levels over 2.0mg/L can cause damage to liver and kidney functions in children and that the dental fluorosis was independent of damage to the liver but not the kidney. Further studies on the mechanisms and significance underlying damage to the liver without dental fluorosis in the exposed children are warranted.

  7. Liver enzymes compared with alcohol consumption in predicting the risk of type 2 diabetes: the Kansai Healthcare Study.

    PubMed

    Sato, Kyoko Kogawa; Hayashi, Tomoshige; Nakamura, Yoshiko; Harita, Nobuko; Yoneda, Takeshi; Endo, Ginji; Kambe, Hiroshi

    2008-06-01

    It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed. The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was >or=126 mg/dl or if participants were taking oral hypoglycemic medications or insulin. During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (>or=42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT. GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes.

  8. Resistance to intravenous immunoglobulin in children with Kawasaki disease

    PubMed Central

    Tremoulet, Adriana H.; Best, Brookie M.; Song, Sungchan; Wang, Susan; Corinaldesi, Elena; Eichenfield, Julia R.; Martin, Danielle D.; Newburger, Jane W.; Burns, Jane C.

    2008-01-01

    Objectives To explore the increased incidence of intravenous immunoglobulin (IVIG) resistance among San Diego County Kawasaki disease (KD) patients in 2006 and to evaluate a scoring system to predict IVIG-resistant patients with KD. Study design We performed a retrospective review of patients with KD treated within 10 days of fever onset. Using multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system. Results In 2006, 38.3 % of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher % bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and γ-glutamyl transferase (GGT). They also had lower platelet counts and age-adjusted hemoglobin (zHgb) concentrations and were more likely to have aneurysms (p=0.0008). A scoring system developed to predict IVIG-resistant patients using illness day, % bands, GGT, and zHgb, had a sensitivity of 73.3% and specificity of 61.9%. Conclusions An unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population. PMID:18571548

  9. Biochemical Effects on the Liver of 1 Month of Alcohol Abstinence in Moderate Alcohol Consumers.

    PubMed

    Munsterman, I D; Groefsema, M M; Weijers, G; Klein, W M; Swinkels, D W; Drenth, J P H; Schellekens, A F A; Tjwa, E T T L

    2018-05-03

    In this study in healthy moderate alcohol consumers, we observe that one month of alcohol abstinence results in decreased gamma-glutamyl transferase levels, which return to baseline levels after resumption of alcohol consumption.

  10. Hb Hope [beta136(H14)Gly-->Asp (GGT-->GAT)]: interactions with Hb S [beta6(A3)Glu-->Val (GAG-->GTG)], other variant hemoglobins and thalassemia.

    PubMed

    Ingle, John; Adewoye, Adeboye; Dewan, Robert; Okoli, Michael; Rollins, Lamarr; Eung, Shawn H; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H

    2004-01-01

    Hb Hope [beta136(H14)Gly-->Asp (GGT-->GAT)] was first described in an African-American family in 1965. Since then, it has been found in combination with several different globin gene mutations in many other families of divergent ethnic backgrounds. The basis for its relatively frequent occurrences remains unexplained. This variant hemoglobin (Hb) is mildly unstable and has reduced oxygen affinity, but is generally innocuous clinically. This variant Hb can present as a confounding factor in arriving at a correct diagnosis by either electrophoresis or high performance liquid chromatography (HPLC), particularly during the neonatal period. DNA-based diagnostics can help solve this potential problem.

  11. Prospective inverse associations of sex hormone concentrations in men with biomarkers of inflammation and oxidative stress.

    PubMed

    Haring, Robin; Baumeister, Sebastian E; Völzke, Henry; Dörr, Marcus; Kocher, Thomas; Nauck, Matthias; Wallaschofski, Henri

    2012-01-01

    The suggested associations between sex hormone concentrations and inflammatory biomarkers in men originate from cross-sectional studies and small-scale clinical trials. But prior studies have not investigated longitudinal associations. Overall, 1344 men aged 20-79 years from the population-based cohort Study of Health in Pomerania were followed up for 5.0 (median) years. We used multivariable regression models to analyze cross-sectional and longitudinal associations of serum sex hormone concentrations (total testosterone [TT], sex hormone-binding globulin [SHBG], calculated free testosterone [free T], and dehydroepiandrosterone sulfate [DHEAS]) with biomarkers of inflammation (fibrinogen, high-sensitive C-reactive protein [hsCRP], and white blood cell count [WBC]) and oxidative stress (γ-glutamyl transferase [GGT]) using ordinary least square regression and generalized estimating equation models, respectively. Cross-sectional models revealed borderline associations of sex hormone concentrations with hsCRP, WBC, and GGT levels that were not retained after multivariable adjustment. Longitudinal multivariable analyses revealed an inverse association of baseline TT, free T, and DHEAS concentrations with change in fibrinogen levels (per SD decrement in TT, 0.25 [95% confidence interval, 0.04-0.45]; in free T, 0.30 [0.09-0.51]; and in DHEAS, 0.23 [0.11-0.36]). Furthermore, baseline DHEAS concentrations were inversely associated with change in WBC levels (per SD decrement, 0.53 [0.24-0.82]). Baseline TT, SHBG, free T, and DHEAS concentrations were also inversely associated with change in GGT after multivariable adjustment. The present study is the first to demonstrate prospective inverse associations between sex hormone concentrations and markers of inflammation and oxidative stress in men. Additional studies are warranted to elucidate potential mechanisms underlying the revealed associations.

  12. High Liver Enzyme Concentrations are Associated with Higher Glycemia, but not with Glycemic Variability, in Individuals without Diabetes Mellitus.

    PubMed

    Noordam, Raymond; Vermond, Debbie; Drenth, Hermijntje; Wijman, Carolien A; Akintola, Abimbola A; van der Kroef, Sabrina; Jansen, Steffy W M; Huurman, Neline C; Schutte, Bianca A M; Beekman, Marian; Slagboom, P Eline; Mooijaart, Simon P; van Heemst, Diana

    2017-01-01

    Elevated concentrations of liver enzymes have been associated with an increased risk of developing type 2 diabetes mellitus. However, it remains unclear to which specific aspects of diurnal glucose metabolism these associate most. We aimed to investigate the associations between liver enzyme concentrations and 24 h-glucose trajectories in individuals without diabetes mellitus from three independent cohorts. This cross-sectional study included 436 participants without diabetes mellitus from the Active and Healthy Aging Study, the Switchbox Study, and the Growing Old Together Study. Fasting blood samples were drawn to measure gamma-glutamyltransferase (GGT), alanine transaminase, and aspartate transaminase. Measures of glycemia (e.g., nocturnal and diurnal mean glucose levels) and glycemic variability (e.g., mean amplitude of glucose excursions) were derived from continuous glucose monitoring. Analyses were performed separately for the three cohorts; derived estimates were additionally meta-analyzed. After meta-analyses of the three cohorts, elevated liver enzyme concentrations, and specifically elevated GGT concentrations, were associated with higher glycemia. More specific, participants in the highest GGT tertile (GGT ≥37.9 U/L) had a 0.39 mmol/L (95% confidence interval: 0.23, 0.56) higher mean nocturnal glucose (3:00 to 6:00 a.m.) and a 0.23 mmol/L (0.10, 0.36) higher diurnal glucose (6:00 to 0:00 a.m.) than participants in the lowest GGT tertile (GGT <21.23 U/L). However, elevated liver enzyme concentrations were not associated with a higher glycemic variability. Though elevated liver enzyme concentrations did not associate with higher glycemic variability in participants without diabetes mellitus, specifically, elevated GGT concentrations associated with higher glycemia.

  13. Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

    PubMed Central

    Mossa, Abdel-Tawab H.; Ibrahim, Faten M.; Mohafrash, Samia M. M.; Abou Baker, Doha H.; El Gengaihi, Souad

    2015-01-01

    The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1 body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1 body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity. PMID:26265923

  14. [Use of fish oil lipid emulsions in hospitalized patients under 18 years old with abnormal results in liver tests associated with total parental nutrition].

    PubMed

    Giraldo Villa, Adriana; Henao Roldan, Catherine; García Loboguerrero, Fanny; Martínez Volkmar, María Isabel; Contreras Ramírez, Mónica María; Ruiz Navas, Patricia

    2014-04-01

    Prolonged Total Parental Nutrition (TPN) is associated with life-threatening complications in the pediatric population, being cholestasis one of the most important ones. The source of fatty acids, the amount of phytosterols and the dose of lipids in the nutritional support, have been linked to the development of this complication. To describe the behavior of liver function tests in pediatric patients with TPN where lipid based omega 3 fatty acids (OmegavenR) were used. A retrospective research was made in a population of children under 18 years old where omega 3 fatty acids were used for a minimum of 8 days. Patients were initially classified into two groups: cholestasis and abnormal liver tests. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB) gamma glutamyl transferase (GGT) and alkaline phosphatase (AP) before and after treatment with OmegavenR was evaluated. 33 patients met the inclusion criteria. At the end of treatment with OmegavenR, 82.4% of patients who initially presented cholestasis showed resolution or improvement. The group of patients with abnormal liver tests 18.8% progressed to cholestasis. Our study suggests that the use of OmegavenR in pediatric patients with TPN and DB ≥ 2 mg/dL, seem to reverse or improve cholestasis while in patients with abnormal liver tests we still don't have clear effect. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  15. Influence of Fasciola hepatica on Serum Biochemical Parameters and Vascular and Biliary System of Sheep Liver

    PubMed Central

    Hodžić, A; Zuko, A; Avdić, R; Alić, A; Omeragić, J; Jažić, A

    2013-01-01

    Background The aim of this study was to evaluate the functional capacity of the liver based on the activity of specific enzymes and bilirubin in serum and also to investigate the influence of mechanical and toxic effects of Fasciola hepatica on the structures of the blood vessels and biliary tract in the sheep liver. Methods Blood samples and liver of 63 indigenous sheep of Pramenka breed, slaughtered in the period from March to December 2009 were used. Based on parasitological findings in the liver, all animals were divided into two groups: control (n = 34) and infected group (n = 29). For investigation and description of pathological changes in sheep liver, naturally infected with F. hepatica, corrosion cast technique was used. Results Biochemical analysis of tested parameters showed a significant elevation (P≤0.05) of serum gamma-glutamyl transferase (GGT), total bilirubin (TBIL) and direct bilirubin (DBIL) in infected sheep group comparing with the control group. No significant differences were observed for activity of aspartate aminotranferase (AST) between groups. Vascular and biliary systems of the liver were found to be affected. Conclusion Results of biochemical analysis are consistent with pathological findings and measuring of tested parameters could be used in early diagnosis of sheep fasciolosis and to test the effectiveness of anthelmintic therapy. Corrosion cast technique is very useful for investigation of pathological changes and neoangiogenesis of vascular and biliary system in sheep liver, caused by mechanical and toxic effects of F. hepatica. PMID:23682266

  16. Serum ischemia modified albumin is a possible new marker of oxidative stress in phenylketonuria.

    PubMed

    Keshavarzi, Fatemeh; Rastegar, Mohsen; Vessal, Mahmood; Rafiei Dehbidi, Gholamreza; Khorsand, Marjan; Ganjkarimi, Amir Hossein; Takhshid, Mohammad Ali

    2018-06-01

    The role of oxidative stress in the pathogenesis of phenylketonuria (PKU)-associated disorders has been implicated. Ischemia modified albumin (IMA) is a modified form of serum albumin, which is produced under the conditions of oxidative stress. The aim of this study was to measure the serum level of IMA in the PKU patients and to investigate its ability in predicting the status of oxidative stress in these patients. Fifty treated-PKU patients and fifty age- and sex-matched healthy subjects were included in the study. The blood samples were obtained and the serum level of phenylalanine (Phe) was measured using reverse phase HPLC method. The levels of IMA, malondialdehyde (MDA), gamma-glutamyl transferase (GGT) activity, and uric acid (UA) were determined using colorimetric methods. The levels of serum Phe, IMA, and MDA were significantly higher (p < 0.001) and the level of UA (p < 0.05) was lower in the PKU patients compared to control group. Serum IMA level was positively correlated with MDA (r = 0.585, p < 0.001) and UA (r = 0.6, p < 0.001). An inverse relationship was observed between the serum level of IMA and Phe (r = - 0.410, p < 0. 01). Results of the present study suggest that serum IMA level could be used as a novel marker for the evaluation of oxidative stress in the PKU patients.

  17. Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study.

    PubMed

    Nannipieri, Monica; Gonzales, Clicerio; Baldi, Simona; Posadas, Rosalinda; Williams, Ken; Haffner, Steven M; Stern, Michael P; Ferrannini, Ele

    2005-07-01

    To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes. From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were < or =3 SDs of the mean population value, alcohol intake was <250 g/week, and hepatitis B and C virus testing was negative. At follow-up (7 years), 94 subjects developed diabetes and 93 impaired glucose tolerance (IGT). At baseline, all four enzymes were related to most of the features of the metabolic syndrome. After controlling for sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood pressure, higher alanine aminotransferase and GGT values were significantly (P < 0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was associated with diabetes only (P = 0.0004) and aspartate aminotransferase with IGT only (P = 0.0001). Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations. Although mild elevations in liver enzymes are associated with features of the metabolic syndrome, only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress.

  18. A novel design of a multi-antigenic, multistage and multi-epitope vaccine against Helicobacter pylori: An in silico approach.

    PubMed

    Meza, Beatriz; Ascencio, Felipe; Sierra-Beltrán, Arturo Pedro; Torres, Javier; Angulo, Carlos

    2017-04-01

    Helicobacter pylori have colonized the gastric mucosa of half of the population worldwide. This bacterium is classified as a definitive type I carcinogen by the World Health Organization and no effective vaccine has been found against it yet. Thus, a logical and rational vaccine design against H. pylori is necessary. Because of its tremendous complexity and elicited immune responses, the vaccine design should considered multiple antigens to enhance immune-protection, involved in the different stages of pathogenesis besides inducing a specific immune response by B- and T-cell multi-epitopes. In this study, emphasis was placed on the design of a new unique vaccine named CTB-multiHp. In silico techniques were used to design a chimeric construct consisting of cholera toxin B subunit fused to multi-epitope of urease B (residue 148-158, 188-198), cytotoxin-associated gene A (residue 584-602), neutrophil activating protein (residue 4-28), vacuolating cytotoxin gene A (residue 63-81), H. pylori adhesine A (residue77-99), heat shock protein A (residue 32-54) and gamma glutamyl transpeptidase (residue 271-293). The tertiary structure and features of the vaccine were analyzed. The chimeric protein was expressed in Escherichia coli BL21 and the serology analyses indicated that the CTB-multiHp protein produced exhibit immune-reactivity. The results showed that CTB-multiHp could be a good vaccine candidate against H. pylori. Ongoing studies will evaluate the effects of CTB-multiHp against H. pylori infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Ameliorative effects of Spirulina platensis against lead-induced nephrotoxicity in newborn rats: Modulation of oxidative stress and histopathological changes

    PubMed Central

    Gargouri, Manel; Soussi, Ahlem; Akrouti, Amel; Magné, Christian; El Feki, Abdelfattah

    2018-01-01

    Our experimental work was aimed at evaluating the safety and protective effects of dietary spirulina supplementation on the kidney of newborn rats, the offspring of lead contaminated lactating mothers. Female rats were randomly divided into four groups: group I (control) was given a normal diet, group II (positive control, S) received a diet enriched with spirulina, group III received only lead through drinking water (Pb), and group IV received both a diet enriched with spirulina and lead contaminated water (S Pb). The treatment of pregnant rats with lead administrated in drinking water, from the 5th day of pregnancy until day 14 after delivery, induced an increased level of renal lipid peroxidation, protein carbonyl, hydrogen peroxide and advanced oxidation protein product, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in newborns. A statistically significant increase of renal DNA, mRNA, hematological parameters as well as in plasma urea and creatinine serum levels and lactate dehydrogenase was seen in pups, while those of uric acid declined. Interestingly, these biochemical modifications were accompanied by a significant decrease of lactate dehydrogenase in kidney, plasma alkaline phosphatase and gamma glutamyl-transpeptidase levels, urinary levels of creatinine and urea. Conversely, supplementation of lead-treated mother's with spirulina alleviated hematotoxicity induced by lead as evidenced, by restoring the biochemical markers cited above to near normal levels. Nevertheless, the distorted histoarchitecture in rat kidney attenuated following spirulina supplementation. It can be then concluded that spirulina is an important protective source against kidney impairments. PMID:29743860

  20. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

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

    Chen, Y.-J.; Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan

    2005-11-15

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses ofmore » CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.« less

  1. Prospective clinical trial of rifaximin therapy for patients with primary sclerosing cholangitis

    PubMed Central

    Tabibian, James H.; Gossard, Andrea; El-Youssef, Mounif; Eaton, John E.; Petz, Jan; Jorgensen, Roberta; Enders, Felicity B.; Lindor, Keith D.

    2014-01-01

    Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease in which emerging data suggest that oral antibiotics may offer therapeutic effects. We enrolled patients with PSC in a 12-week open-label pilot study to investigate the efficacy and safety of oral rifaximin 550 mg twice daily. The primary endpoint was serum alkaline phosphatase (ALK) at 12 weeks. Secondary endpoints included: i) serum bilirubin, gamma-glutamyl transpeptidase, and Mayo PSC risk score; ii) Fisk Fatigue Impact Scale (FFIS), Chronic Liver Disease Questionnaire (CLDQ), and Short Form Health Survey (SF-36) scores; and iii) adverse effects (AEs). Analyses were performed with nonparametric tests. Sixteen patients were enrolled, among whom the median age was 40 years, 13 (81%) were male, 13 had inflammatory bowel disease, and baseline ALK was 342 IU/mL (interquartile range 275-520). Following 12 weeks of treatment, there were no significant changes in ALK (median increase of 0.9% to 345 IU/mL, p=0.47) or any of the secondary biochemical endpoints (all p>0.05). Similarly, there were no significant changes in FFIS, CLDQ, or SF-36 scores (all p>0.05). Three patients withdrew from the study due to AEs; four others reported mild AEs but completed the study. In conclusion, while some antibiotics may have promise in treating PSC, oral rifaximin, based on the results herein, appears inefficacious for this indication. Future studies are needed to understand how the antimicrobial spectra and other properties of antibiotics might determine their utility in treating PSC. (clinicaltrials.gov NCT01695174) PMID:24914504

  2. Short-term systemic effects of nose-only cigarette smoke exposure in mice: role of oxidative stress.

    PubMed

    Nemmar, Abderrahim; Raza, Haider; Subramaniyan, Deepa; Yasin, Javed; John, Annie; Ali, Badreldin H; Kazzam, Elsadig E

    2013-01-01

    Long-term cigarette smoking (CS) is a major risk factor for respiratory and cardiovascular diseases, and is also known to adversely affect other organs. However, data on the systemic effects of short-term CS exposure (STCSE) are scarce. Presently, using a nose-only exposure system, we evaluated the systemic effects of STCSE in mice. We assessed the effects of CS generated by 9 consecutive cigarettes per day for 4 days in a nose-only exposure system on cardiovascular, hepatic and renal endpoints evaluated on day 5 in mice. Control mice were exposed to air only. CS significantly increased systolic blood pressure and decreased total nitric oxide plasma concentration. Circulating platelets and erythrocyte numbers were also increased. However, STCSE did not significantly increase thrombosis in pial arterioles and venules. STCSE significantly raised plasma alanine aminotransferase and gamma glutamyl transpeptidase activities, but did not affect urea or creatinine concentrations. Interestingly, while STCSE enhanced the production of reactive oxygen species in heart and kidney and lipid peroxidation in heart, liver and kidneys, it also enhanced the antioxidant activity of superoxide dismutase, probably indicating that STCSE causes adaptive reactions to counterbalance the potentially damaging action of oxygen radicals induced by STCSE. These results suggest that STCSE causes blood pressure increase, hepatotoxicity and oxidative stress in the heart, liver and the kidneys. These data provide information on the initial steps leading to the systemic effects of STCSE, a stage at which the diseases may likely be reversed. Copyright © 2012 S. Karger AG, Basel.

  3. Treatment with nandrolone decanoate and megestrol acetate in HIV-infected men.

    PubMed

    Cuerda, Cristina; Zugasti, Ana; Bretón, Irene; Camblor, Miguel; Miralles, Pilar; García, Pilar

    2005-02-01

    Malnutrition, especially loss of lean body mass, is a frequent complication of people living with HIV that may increase their mortality and morbidity. Nine HIV-infected men with unexplained loss of >10% of their usual weight were selected. They received megestrol acetate (MA) (400 mg/day by mouth) and nandrolone decanoate (ND) (100 mg/15 days intermuscular injection) over 16 weeks. Anthropometric evaluations, bioelectrical impedance, grip strength dynamometry, hematologic, biochemical, immunological and hormonal analysis before, during, and after the treatment were performed. Quality of life was evaluated by the Karnofsky index. In the 7 men that finished the treatment, there were significant increases in weight (11.9 +/- 9.1 kg, p < .05), 4-site skinfold measurements (p < .05), midarm circumference (p < .005), and fat-free mass (FFM) (5.1 +/- 4.1 kg, p < .05). The increase in fat mass was not statistically significant (6.9 +/- 6.4 kg, NS). Muscle strength increased significantly (p < .005). The Karnofsky index values increased from 59% to 73% (p < .05). One patient developed mild hyperglycemia and another one had an increase in aspartate transaminase and gamma-glutamyl transpeptidase that reversed after the treatment. Four patients developed asymptomatic adrenal suppression. Testosterone serum levels decreased significantly during the study (p < .05), and 4 patients had serum values below the normal range at week 16. One patient developed gynecomastia. The combined treatment with MA and ND led to a significant increase in body weight and FFM. Muscle strength and quality of life improved during the study. The treatment was well tolerated with mild side effects.

  4. Eudragit RS 100 microparticles containing 2-hydroxypropyl-beta-cyclodextrin and glutathione: physicochemical characterization, drug release and transport studies.

    PubMed

    Trapani, Adriana; Laquintana, Valentino; Denora, Nunzio; Lopedota, Angela; Cutrignelli, Annalisa; Franco, Massimo; Trapani, Giuseppe; Liso, Gaetano

    2007-01-01

    The aim of this study was to encapsulate glutathione (GSH) alone or in combination with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in Eudragit RS 100 microparticles (MPs), and to evaluate these novel delivery systems for oral administration of the considered tripeptide. The MPs were prepared by an O/O emulsion-solvent evaporation method according to a multilevel experimental design involving the volume of liquid paraffin, the HP-beta-CD amount, and the drug/polymer ratio as independent variables. The effects of these parameters on particle size, entrapment efficiency, and drug release were investigated. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GSH and Eudragit RS 100 polymer and to characterize the physical state of drug within the MPs. The release profiles of GSH from MPs were examined in vitro at pH 1.2, 6.8. and 7.4 using the USP III (BioDis) dissolution apparatus. In general, a slow and zero-order release of GSH from MPs at pH 1.2 occurred, while at higher pH values considerable amounts of glutathione disulfide (i.e., GSSG) were observed. The enzymatic stability and the intestinal permeability of some GSH-containing MPs were assessed by using pepsin, alpha-chymotrypsin, gamma-glutamyl-transpeptidase and everted frog intestinal sac methodology, respectively. The results suggest that GSH-loaded Eudragit RS 100 MPs containing HP-beta-CD represent a new sustained GSH delivery system useful for the oral administration of the examined tripeptide.

  5. 1,2,3,4-Tetrahydroisoquinoline protects terminals of dopaminergic neurons in the striatum against the malonate-induced neurotoxicity.

    PubMed

    Lorenc-Koci, Elzbieta; Gołembiowska, Krystyna; Wardas, Jadwiga

    2005-07-27

    Malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, is frequently used as a model neurotoxin to produce lesion of the nigrostriatal dopaminergic system in animals due to particular sensitivity of dopamine neurons to mild energy impairment. This model of neurotoxicity was applied in our study to explore neuroprotective potential of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous substance whose function in the mammalian brain, despite extensive studies, has not been elucidated so far. Injection of malonate at a dose of 3 mumol unilaterally into the rat left medial forebrain bundle resulted in the 54% decrease in dopamine (DA) concentration in the ipsilateral striatum and, depending on the examined striatum regions, caused 24-44% reduction in [3H]GBR12,935 binding to the dopamine transporter (DAT). TIQ (50 mg/kg i.p.) administered 4 h before malonate infusion and next once daily for successive 7 days prevented both these effects of malonate. Such TIQ treatment restored DA content and DAT binding almost to the control level. The results of the present study indicate that TIQ may act as a neuroprotective agent in the rat brain. An inhibition of the enzymatic activities of monoamine oxidase and gamma-glutamyl transpeptidase as well as an increase in the striatal levels of glutathione and nitric oxide found after TIQ administration and reported in our earlier studies are considered to be potential factors that may be involved in the TIQ-mediated protection of dopamine terminals from malonate toxicity.

  6. Evaluation of liver enzyme levels and identification of asymptomatic liver disease patients in primary care.

    PubMed

    Cacciola, Irene; Scoglio, Riccardo; Alibrandi, Angela; Squadrito, Giovanni; Raimondo, Giovanni

    2017-03-01

    The evaluation of serum liver enzyme levels is the most used surrogate marker of liver injury in clinical practice. The prevalence and association of abnormal enzyme values with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and with other major causes of liver damage (obesity, diabetes, dyslipidemia, and alcohol abuse) were evaluated in individuals attending the surgeries of 14 general practitioners (GPs) working in Messina. Alanine-amino-transferase, aspartate-amino-transferase, and gamma-glutamyl-transpeptidase measurements were measured in 7816 individuals consecutively attending the GP surgeries between January 1, 2011 and June 30, 2012. Five-thousand-eight-hundred-six subjects (74.3 %) had the tests performed, and 1189 of them (20.5 %) showed increased liver enzyme levels. Sixty-nine of these 1189 individuals (5.8 %) were HCV positive and 12 HBV positive (1 %), 755 (63.5 %) were overweight or obese, 288 (24.2 %) had diabetes, and 351 (29.5 %) had dyslipidemia; 262 (22 %) drank >2 alcoholic units/day. Overall, 57 % of individuals with abnormal liver enzymes had multiple possible causes of liver disease, 28 % one cause, and 15 % no apparent cause. In conclusion, this study shows that 1/5 of individuals attending GP surgeries have altered liver biochemistry and that overweight and metabolic disorders have become the major causes of liver damage even in South Italy, where HBV and HCV were endemic in the past century. Notably, many HCV and HBV patients are still unaware of their infected status, and GPs are essential for their timely identification.

  7. Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation.

    PubMed

    Sampaziotis, Fotios; de Brito, Miguel Cardoso; Madrigal, Pedro; Bertero, Alessandro; Saeb-Parsy, Kourosh; Soares, Filipa A C; Schrumpf, Elisabeth; Melum, Espen; Karlsen, Tom H; Bradley, J Andrew; Gelson, William Th; Davies, Susan; Baker, Alastair; Kaser, Arthur; Alexander, Graeme J; Hannan, Nicholas R F; Vallier, Ludovic

    2015-08-01

    The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.

  8. Cell Damage, Antioxidant Status, and Cortisol Levels Related to Nutrition in Ski Mountaineering During a Two-Day Race

    PubMed Central

    Diaz, Elena; Ruiz, Fatima; Hoyos, Itziar; Zubero, Jaime; Gravina, Leyre; Gil, Javier; Irazusta, Jon; Gil, Susana Maria

    2010-01-01

    The aim of this study was to measure the effect of nutrition on cell damage, antioxidant enzymes, and cortisol during a two-day ski mountaineering competition. Twenty-one male skiers participated in the study. Creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), cortisol and C-reactive protein (CRP), glutathione peroxidase (GPx) and reductase activities (GR) and C-reactive protein (CRP) levels, total antioxidant status, and cortisol levels were measured in serum the day before and immediately after the race. Their diet was also analysed during the competition. Enzymes and cortisol levels significantly increased after the competition. CK and LDH and cortisol levels were negatively correlated to total energy, protein, and fat intake. Intake of vitamin A, B1, B2, B6 and niacin was negatively correlated to LDH and AP. A negative correlation was also found between CK activity and Na, Fe, and Zn intake. Cortisol levels were negatively correlated to the intake of vitamins C, B1 and B2, and niacin. A positive correlation was found between serum GPx and intake of energy, carbohydrates, proteins, A and B vitamins, and folic acid. Skiers with the lowest nutrient intake during the competition were the ones who showed greater cell damage and lower antioxidant enzyme activity and cortisol levels, which may impair performance and also cause injuries and accidents. Particularly, skiers should have high intakes of total energy, macronutrients, vitamins A and B, Na, Zn, and Fe in order to decrease the deleterious effect of strenuous exercise. Key points A two-day ski mountaineering race produced muscle cell damage and oxidative stress and an increase in cortisol levels. There was a marked insufficient intake of carbohydrates which has been shown to affect performance Those skiers with lowest nutrient intake showed greater cell damage, lower antioxidant

  9. The relationship between 25-hydroxyvitamin D concentration and liver enzymes in overweight or obese adults: Cross-sectional and interventional outcomes.

    PubMed

    Naderpoor, Negar; Mousa, Aya; de Courten, Maximilian; Scragg, Robert; de Courten, Barbora

    2018-03-01

    Vitamin D deficiency is prevalent in individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. However, there is limited and inconsistent data on the effect of vitamin D supplementation on liver function. Hepatic enzymes have been used as surrogate markers for NAFLD and have been associated with metabolic syndrome. We examined the relationships between 25-hydroxyvitamin D (25(OH)D) and γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in 120 drug-naïve individuals with no history of liver disease. In addition, the effect of vitamin D supplementation (100,000 loading dose of cholecalciferol followed by 4000IU daily for 16 weeks) on hepatic enzymes was investigated in a subgroup of 54 vitamin D-deficient overweight or obese individuals (28 randomised to cholecalciferol and 26 to placebo). Hepatic enzymes, anthropometric parameters, lipid profile, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, M value) and high sensitivity C-reactive protein (hs-CRP) were measured before and after the intervention. In the cross-sectional study, levels of GGT and ALT were higher in men compared to women (both p=0.001). There were no significant differences in GGT, ALT and ALP between vitamin D categories (25(OH)D<25nmol/L, 25-50nmol/L, and >50nmol/L) and no relationships were found between the three enzymes and 25(OH)D before and after adjustment for age, sex, BMI, WHR, and insulin sensitivity (all p>0.5). In the randomised trial, 25(OH)D concentrations increased in the vitamin D group (mean change 57.0±21.3nmol/L) compared to the placebo group (mean change 1.9±15.1nmol/L). Mean changes in GGT, ALT and ALP were not significantly different between vitamin D and placebo groups (all p>0.2). Change in 25(OH)D concentration was not correlated with changes in GGT, ALT and ALP before and after adjustments for age and sex (all p>0.1). In summary, 25(OH)D concentrations were not related to hepatic enzymes

  10. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.

    PubMed

    Olson, Christine A; Vuong, Helen E; Yano, Jessica M; Liang, Qingxing Y; Nusbaum, David J; Hsiao, Elaine Y

    2018-06-14

    The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Examination of the relationships between environmental exposures to volatile organic compounds and biochemical liver tests: application of canonical correlation analysis

    PubMed Central

    Liu, Jing; Drane, Wanzer; Liu, Xuefeng; Wu, Tiejian

    2009-01-01

    This study was to explore the relationships between personal exposure to ten volatile organic compounds (VOCs) and biochemical liver tests with the application of canonical correlation analysis. Data from a subsample of the 1999–2000 National Health and Nutrition Examination Survey were used. Serum albumin, total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) served as the outcome variables. Personal exposures to benzene, chloroform, ethylbenzene, tetrachloroethene, toluene, trichloroethene, o-xylene, m-, p-xylene, 1,4-dichlorobenzene, and methyl tert-butyl ether (MTBE) were assessed through the use of passive exposure monitors worn by study participants. The first two canonical correlations were 0.3218 and 0.2575, suggesting a positive correlation mainly between the six VOCs (benzene, ethylbenzene, toluene, o-xylene, m-, p-xylene, and MTBE) and the three biochemical liver tests (albumin, ALP, and GGT) and a positive correlation mainly between the two VOCs (1,4-dichlorobenzene and tetrachloroethene) and the two biochemical liver tests (LDH and TB). Subsequent multiple linear regressions show that exposure to benzene, toluene, or MTBE was associated with serum albumin, while exposure to tetrachloroethene was associated with LDH and total bilirubin. In conclusion, exposure to certain VOCs as a group or individually may influence certain biochemical liver test results in the general population. PMID:19117555

  12. Z{gamma}{gamma}{gamma} {yields} 0 Processes in SANC

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

    Bardin, D. Yu., E-mail: bardin@nu.jinr.ru; Kalinovskaya, L. V., E-mail: kalinov@nu.jinr.ru; Uglov, E. D., E-mail: corner@nu.jinr.ru

    2013-11-15

    We describe the analytic and numerical evaluation of the {gamma}{gamma} {yields} {gamma}Z process cross section and the Z {yields} {gamma}{gamma}{gamma} decay rate within the SANC system multi-channel approach at the one-loop accuracy level with all masses taken into account. The corresponding package for numeric calculations is presented. For checking of the results' correctness we make a comparison with the other independent calculations.

  13. Sneaky Gamma-Rays: Using Gravitational Lensing to Avoid Gamma-Gamma-Absorption

    NASA Astrophysics Data System (ADS)

    Boettcher, Markus; Barnacka, Anna

    2014-08-01

    It has recently been suggested that gravitational lensing studies of gamma-ray blazars might be a promising avenue to probe the location of the gamma-ray emitting region in blazars. Motivated by these prospects, we have investigated potential gamma-gamma absorption signatures of intervening lenses in the very-high-energy gamma-ray emission from lensedblazars. We considered intervening galaxies and individual stars within these galaxies. We find that the collective radiation field of galaxies acting as sources of macrolensing are not expected to lead to significant gamma-gamma absorption. Individual stars within intervening galaxies could, in principle, cause a significant opacity to gamma-gamma absorption for VHE gamma-rays if the impact parameter (the distance of closest approach of the gamma-ray to the center of the star) is small enough. However, we find that the curvature of the photon path due to gravitational lensing will cause gamma-ray photons to maintain a sufficiently large distance from such stars to avoid significant gamma-gamma absorption. This re-inforces the prospect of gravitational-lensing studies of gamma-ray blazars without interference due to gamma-gamma absorption due to the lensing objects.

  14. Dynamic of oxidative and nitrosative stress markers during the convalescent period of stroke patients undergoing rehabilitation.

    PubMed

    Manolescu, Bogdan Nicolae; Berteanu, M; Oprea, E; Chiriac, N; Dumitru, L; Vladoiu, S; Popa, O; Ianas, O

    2011-07-01

    Stroke patients have a redox imbalance, a consequence of both the cerebrovascular event and the associated pathological conditions. Our study was aimed to investigate the dynamic of some oxidative and nitrosative markers during the convalescent phase of postacute stroke patients undergoing rehabilitation. We assessed thiol, advanced oxidation protein product, protein carbonyl, 3-nitro-l-tyrosine, ceruloplasmin and oxidized LDL concentrations, as well as gamma-glutamyltranspeptidase (GGT) activity in 20 patients at the beginning of the hospitalization and at the discharge moment, respectively, and 24 apparently healthy controls. We found significantly increased values for GGT (P = 0.04), ceruloplasmin (P = 0.01) and protein carbonyl (P = 0.04) in stroke patients at the hospitalization moment when compared with healthy controls, while total thiols were significantly decreased (P = 0.002). Rehabilitation was associated with a significant decrease of protein carbonyl (P = 0.03) and oxidized LDL particle concentrations (P = 0.03), as well as GGT activity (P = 0.02). At the hospitalization moment, both GGT and ceruloplasmin were significantly negatively correlated with non-proteic thiols (r = -0.44, P = 0.049, and r = -0.53, P = 0.015, respectively) and significantly positively with protein carbonyls (r = +0.80, P < 0.001, and r = +0.69, P < 0.001, respectively) suggesting putative roles of GGT and ceruloplasmin in the redox imbalance. These results highlight the existence of a redox imbalance in postacute stroke patients, and the possible benefits of an antioxidant-based therapy for the recovery of these patients.

  15. Evaluation of the Protective Role of Vitamin C on the Metabolic and Enzymatic Activities of the Liver in the Male Rats After Exposure to 2.45 GHz Of Wi-Fi Routers.

    PubMed

    Shekoohi-Shooli, F; Mortazavi, S M J; Shojaei-Fard, M B; Nematollahi, S; Tayebi, M

    2016-09-01

    The use of devices emitted microwave radiation such as mobile phones, wireless fidelity (Wi-Fi) routers, etc. is increased rapidly. It has caused a great concern; the researchers should identify its effects on people's health. We evaluated the protective role of Vitamin C on the metabolic and enzymatic activities of the liver after exposure to Wi-Fi routers. 70 male Wistar rats weighing 200-250 g were randomly divided into 7 groups (10 rats in each group).The first stage one -day test: Group A (received vitamin C 250 mg/kg/day orally together with 8- hour/day Wi-Fi exposure).Group B (exposed to Wi-Fi radiation). Group C (received vitamin C). Group D or Control (was neither exposed to radiation of Wi-Fi modem nor did receive vitamin C). The second phase of experiment had done for five consecutive days. It involved Group E (received vitamin C), Group F (exposed to Wi-Fi radiation), Group G (received vitamin C together with Wi-Fi radiation). The distance between animals' restrainers was 20 cm away from the router antenna. Finally, blood samples were collected and assayed the level of hepatic enzymes including alkaline phosphatase(ALP), alanine amino transferase(ALT) aspartate amino transferase (ASL), gamma glutamyl transferase (GGT) and the concentration of Blood Glucose, Cholesterol , Triglyceride(TG),High density lipoprotein (HDL)and low density lipoprotein (LDL). Data obtained from the One day test showed an increase in concentration of blood glucose, decrease in Triglyceride level and GGT factor (P<0.05), however no observed significant difference on the Cholesterol , HDL , LDL level and hepatic enzymes activities in compare to control group. Groups of the five-day test showed reduction in the amount of blood glucose, elevation of cholesterol level and LDL relative to control group(P<0.05). WiFi exposure may exert alternations on the metabolic parameters and hepatic enzymes activities through stress oxidative and increasing of free radicals, but the use of vitamin

  16. Evaluation of the Protective Role of Vitamin C on the Metabolic and Enzymatic Activities of the Liver in the Male Rats After Exposure to 2.45 GHz Of Wi-Fi Routers

    PubMed Central

    Shekoohi-Shooli, F.; Mortazavi, S.M.J.; Shojaei-fard, M.B.; Nematollahi, S.; Tayebi, M.

    2016-01-01

    Background: The use of devices emitted microwave radiation such as mobile phones, wireless fidelity (Wi-Fi) routers, etc. is increased rapidly. It has caused a great concern; the researchers should identify its effects on people’s health. We evaluated the protective role of Vitamin C on the metabolic and enzymatic activities of the liver after exposure to Wi-Fi routers. Material and Methods: 70 male Wistar rats weighing 200-250 g were randomly divided into 7 groups (10 rats in each group).The first stage one -day test: Group A (received vitamin C 250 mg/kg/day orally together with 8- hour/day Wi-Fi exposure).Group B (exposed to Wi-Fi radiation). Group C (received vitamin C). Group D or Control (was neither exposed to radiation of Wi-Fi modem nor did receive vitamin C). The second phase of experiment had done for five consecutive days. It involved Group E (received vitamin C), Group F (exposed to Wi-Fi radiation), Group G (received vitamin C together with Wi-Fi radiation). The distance between animals’ restrainers was 20 cm away from the router antenna. Finally, blood samples were collected and assayed the level of hepatic enzymes including alkaline phosphatase(ALP), alanine amino transferase(ALT) aspartate amino transferase (ASL), gamma glutamyl transferase (GGT) and the concentration of Blood Glucose, Cholesterol , Triglyceride(TG),High density lipoprotein (HDL)and low density lipoprotein (LDL). Results: Data obtained from the One day test showed an increase in concentration of blood glucose, decrease in Triglyceride level and GGT factor (P<0.05), however no observed significant difference on the Cholesterol , HDL , LDL level and hepatic enzymes activities in compare to control group. Groups of the five-day test showed reduction in the amount of blood glucose, elevation of cholesterol level and LDL relative to control group(P<0.05). Conclusion: WiFi exposure may exert alternations on the metabolic parameters and hepatic enzymes activities through stress

  17. Hepatic photosensitization in buffaloes intoxicated by Brachiaria decumbens in Minas Gerais state, Brazil.

    PubMed

    De Oliveira, C H S; Barbosa, J D; Oliveira, C M C; Bastianetto, E; Melo, M M; Haraguchi, M; Freitas, L G L; Silva, M X; Leite, R C

    2013-10-01

    The aim of this paper is to report the study of hepatogenous photosensitization in buffaloes during two outbreaks provoked by ingestion of Brachiaria decumbens in Minas Gerais state, Brazil. Ten young buffaloes in outbreak 1 and seven buffaloes in outbreak 2 were intoxicated by B. decumbens. Nine clinically healthy buffaloes raised under the same conditions as the sick animals served as the control group. All animals were subjected to clinical examination, and serum was collected to measure gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), direct bilirubin (DB), indirect bilirubin (IB) and total bilirubin (TB) as indicators of liver function and urea and creatinine as indicators of renal function. Histopathology of liver fragments from five different animals was carried out. During the outbreaks and every two months for one year, samples of grass from paddocks where the animals got sick were collected for quantitative evaluation of the saponin protodioscin, combined with observations of pasture characteristics and daily rainfall. Clinical signs included apathy, weight loss, restlessness, scar retraction of the ears and intense itching at the skin lesions, mainly on the rump, the tail head, neck and hindlimbs, similar to the signs observed in other ruminants. Only the GGT enzyme presented significantly different (P < 0.01) serum levels between intoxicated animals (n = 17) and healthy animals (n = 9), indicating liver damage in buffaloes bred in B. decumbens pastures. Microscopy of the liver showed foamy macrophages and lesions of liver disease associated with the presence of crystals in the bile ducts, which have also been found in sheep and cattle poisoned by grasses of the genus Brachiaria. During the outbreaks, protodioscin levels were higher than 3%, and shortly after, these levels were reduced to less than 0.80%, suggesting a hepatic injury etiology. The outbreaks took place at the beginning of the rainy season, and there was a positive

  18. Antiurolithiatic Effect of Sirupeelai Samoola Kudineer: A Polyherbal Siddha Decoction on Ethylene Glycol-induced Renal Calculus in Experimental Rats

    PubMed Central

    Vasanthi, A. Hannah Rachel; Muthulakshmi, V.; Gayathri, V.; Manikandan, R.; Ananthi, S.; Kuruvilla, Sarah

    2017-01-01

    functional protection against ethylene glycol- induced renal calculus in rats as evidenced by histopathological studies. Abbreviations used: SK: Sirupeelai Samoola Kudineer; TBARS: ThioBarbituric Acid Reactive Substances; SOD: SuperOxide Dismutase; GPx: Gluthathione peroxidase; GSH- Glutathione; LPO: Lipid peroxidation as measured as TBARS; AST: Aspartate AminoTransferase; ALT: Alanine Amino transferase; GGT: Gamma Glutamyl Transferase; LDH: Lactate Dehydrogenase. PMID:28808392

  19. Sorting nexin Snx41 is essential for conidiation and mediates glutathione-based antioxidant defense during invasive growth in Magnaporthe oryzae

    PubMed Central

    Deng, Yi Zhen; Qu, Ziwei; He, Yunlong; Naqvi, Naweed I.

    2012-01-01

    The sorting nexins Atg20/Snx42 and Snx41 regulate membrane traffic and endosomal protein sorting and are essential for Cvt and/or pexophagy in yeast. Previously, we showed that macroautophagy is necessary for conidiation in the rice-blast fungus Magnaporthe oryzae. Here, we analyzed the physiological function(s) of selective autophagy in Magnaporthe through targeted deletion of MGG_12832, an ortholog of yeast SNX41 and ATG20/SNX42. Loss of MGG_12832 (hereafter SNX41) abolished conidia formation and pathogenesis in M. oryzae. Snx41-GFP localized as dynamic puncta or short tubules that are partially associated with autophagosomes and/or autophagic vacuoles. PX domain, but not macroautophagy per se, was required for such localization of Snx41-GFP in Magnaporthe. Although not required for nonselective autophagy, Snx41 was essential for pexophagy in Magnaporthe. We identified Oxp1, an ATP-dependent oxoprolinase in the gamma-glutamyl cycle, as a binding partner and potential retrieval target of Snx41-dependent protein sorting. The substrate of Oxp1, 5-oxoproline, could partially restore conidiation in the snx41Δ. Exogenous glutathione, a product of the gamma-glutamyl cycle, significantly restored pathogenicity in the snx41Δ mutant, likely through counteracting the oxidative stress imposed by the host. We propose that the gamma-glutamyl cycle and glutathione biosynthesis are subject to regulation by Snx41-dependent vesicular trafficking, and mediate antioxidant defense crucial for in planta growth and pathogenic differentiation of Magnaporthe at the onset of blast disease in rice. PMID:22561104

  20. Prevalence and Predictors of Abnormal Liver Enzymes in Young Women with Anorexia Nervosa

    PubMed Central

    Fong, Hiu-fai; DiVasta, Amy D.; DiFabio, Diane; Ringelheim, Julie; Jonas, Maureen M.; Gordon, Catherine M.

    2008-01-01

    Objective To determine the prevalence and predictors of abnormal liver enzyme levels in ambulatory young women with anorexia nervosa (AN). Study design In this cross-sectional study of 53 females with AN, serum concentrations of liver enzymes and hormones were measured. Anthropometric, dietary, and body composition information was collected. Correlational analyses were performed between liver enzyme concentrations and these variables. Results Elevated alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels were found in 14 subjects (26%) and 5 subjects (9%), respectively. ALT and GGT were inversely correlated with body mass index (r = −0.27 to −0.30, p ≤ 0.049) and percentage body fat (r = −0.36 to −0.47, p ≤ 0.007), but showed no relationship with lean body mass. Subjects with percentage body fat < 18% had higher ALT levels than those above this threshold (median 26.5 vs. 18.0 U/L, p = 0.01). Liver enzyme concentrations did not correlate with dietary variables, except for GGT and percentage of calories from protein (r = 0.28, p = 0.04). Conclusions Serum ALT and GGT concentrations are inversely related to adiposity in young women with AN. Future studies are needed to determine if these liver enzyme elevation signify unrecognized, clinically relevant liver disease. PMID:18534220

  1. Association between liver function and metabolic syndrome in Chinese men and women

    PubMed Central

    Wang, Sen; Zhang, Jie; Zhu, Li; Song, Linlin; Meng, Zhaowei; Jia, Qiang; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Zhang, Qing; Liu, Li; Song, Kun; Jia, Qiyu

    2017-01-01

    Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS. PMID:28317840

  2. [Prediction of histological liver damage in asymptomatic alcoholic patients by means of clinical and laboratory data].

    PubMed

    Iturriaga, H; Hirsch, S; Bunout, D; Díaz, M; Kelly, M; Silva, G; de la Maza, M P; Petermann, M; Ugarte, G

    1993-04-01

    Looking for a noninvasive method to predict liver histologic alterations in alcoholic patients without clinical signs of liver failure, we studied 187 chronic alcoholics recently abstinent, divided in 2 series. In the model series (n = 94) several clinical variables and results of common laboratory tests were confronted to the findings of liver biopsies. These were classified in 3 groups: 1. Normal liver; 2. Moderate alterations; 3. Marked alterations, including alcoholic hepatitis and cirrhosis. Multivariate methods used were logistic regression analysis and a classification and regression tree (CART). Both methods entered gamma-glutamyltransferase (GGT), aspartate-aminotransferase (AST), weight and age as significant and independent variables. Univariate analysis with GGT and AST at different cutoffs were also performed. To predict the presence of any kind of damage (Groups 2 and 3), CART and AST > 30 IU showed the higher sensitivity, specificity and correct prediction, both in the model and validation series. For prediction of marked liver damage, a score based on logistic regression and GGT > 110 IU had the higher efficiencies. It is concluded that GGT and AST are good markers of alcoholic liver damage and that, using sample cutoffs, histologic diagnosis can be correctly predicted in 80% of recently abstinent asymptomatic alcoholics.

  3. Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

    USDA-ARS?s Scientific Manuscript database

    The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

  4. The Z {yields} cc-bar {yields} {gamma}{gamma}*, Z {yields} bb-bar {yields} {gamma}{gamma}* triangle diagrams and the Z {yields} {gamma}{psi}, Z {yields} {gamma}Y decays

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

    Achasov, N. N., E-mail: achasov@math.nsc.ru

    2011-03-15

    The approach to the Z {yields} {gamma}{psi} and Z {yields} {gamma}Y decay study is presented in detail, based on the sum rules for the Z {yields} cc-bar {yields} {gamma}{gamma}* and Z {yields} bb-bar {yields} {gamma}{gamma}* amplitudes and their derivatives. The branching ratios of the Z {yields} {gamma}{psi} and Z {yields} {gamma}Y decays are calculated for different hypotheses on saturation of the sum rules. The lower bounds of {Sigma}{sub {psi}} BR(Z {yields} {gamma}{psi}) = 1.95 Multiplication-Sign 10{sup -7} and {Sigma}{sub {upsilon}} BR(Z {yields} {gamma}Y) = 7.23 Multiplication-Sign 10{sup -7} are found. Deviations from the lower bounds are discussed, including the possibilitymore » of BR(Z {yields} {gamma}J/{psi}(1S)) {approx} BR(Z {yields} {gamma}Y(1S)) {approx} 10{sup -6}, that could be probably measured in LHC. The angular distributions in the Z {yields} {gamma}{psi} and Z {yields} {gamma}Y decays are also calculated.« less

  5. Association between Healthy Eating Index-2010 and Fetuin-A Levels in Patients with Type 2 Diabetes: a Case-Control Study.

    PubMed

    Roshanzamir, Farzad; Miraghajani, Maryam; Mansourian, Marjan; Ghiasvand, Reza; Safavi, Seyyed Morteza

    2017-10-01

    The Healthy Eating Index-2010 (HEI-2010) assesses compliance with the 2010 Dietary Guidelines for Americans. Studies suggest that adherence to the HEI-2010 is related to lower the risk of type 2 diabetes (T2D). Fetuin-A, a novel biomarker for T2D, may play a linking role in the inverse association between HEI-2010 and T2D. Thus, a case-control analysis involving 107 patients with T2D and107 healthy subjects was conducted to determine the association between HEI-2010 and serum fetuin-A levels. The results of simple regression analysis showed that fetuin-A levels were positively associated with full name of body mass index (BMI) (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (FBG) (p < 0.001), triglycerides (TG) (p = 0.003), gamma-glutamyl transferase (GGT) (p < 0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) (p =0.001) and negatively associated with physical activity (PA) (p < 0.001), high-density lipoprotein (HDL) (p = 0.022), and HEI-2010 (p < 0.001) in all subjects. After controlling for confounders, the inverse association between fetuin-A and HEI-2010 remained significant in the subjects with T2D (β = -0.386; p < 0.001), 107 healthy controls (β = -0.237; p = 0.028), and all subjects (β = -0.298; p < 0.001). In conclusion, the present results suggested that higher quality diet assessed by HEI-2010 associates with lower serum fetuin-A levels in people with and without T2D. More studies are needed to confirm these findings.

  6. The correlates of urinary albumin to creatinine ratio (ACR) in a high risk Australian aboriginal community.

    PubMed

    Wang, Zaimin; Hoy, Wendy E; Wang, Zhiqiang

    2013-08-16

    Albuminuria marks renal disease and cardiovascular risk. It was estimated to contribute 75% of the risk of all-cause natural death in one Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an index of albuminuria. This study aims to examine the associations between demographic factors, anthropometric index, blood pressure, lipid-protein measurements and other biomarkers and albuminuria in a cross-sectional study in a high-risk Australian Aboriginal population. The models will be evaluated for albuminuria at or above the microalbuminuria threshold, and at or above the "overt albuminuria" threshold with the potential to distinguish associations they have in common and those that differ. This was a cross-sectional study of 598 adults aged 18-76 years. All participants were grouped into quartiles by age. Logistic regression models were used to explore the correlates of ACR categories. The significant correlates were systolic blood pressure (SBP), C-reactive protein (CRP), uric acid, diabetes, gamma-glutamyl transferase (GGT) (marginally significant, p=0.054) and serum albumin (negative association) for ACR 17+ (mg/g) for men and 25+ for women. Independent correlates were SBP, uric acid, diabetes, total cholesterol, alanine amino transferase (ALT), Cystatin C and serum albumin (negative association) for overt albuminuria; and SBP, CRP and serum albumin only for microalbuminuria. This is the most detailed modelling of pathologic albuminuria in this setting to date. The somewhat variable association with risk factors suggests that microalbuminuria and overt albuminuria might reflect different as well as shared phenomena.

  7. Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

    PubMed

    Longo-Mbenza, Benjamin; Mvitu Muaka, Moise; Masamba, Wayiza; Muizila Kini, Lucien; Longo Phemba, Igor; Kibokela Ndembe, Dalida; Tulomba Mona, Doris

    2014-01-01

    To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM.

  8. Carcinogenicity of by-products of disinfection in mouse and rat liver

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

    Herren-Freund, S.L.; Pereira, M.A.

    1986-11-01

    By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of ..gamma..-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylene, and N-Cl piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform either hadmore » no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-days-old Swiss mice initiated with ethylnitrosourea (ENU). ENU at 5 and 20 ..mu..g/g caused a dose-dependent increase in liver tumors. In male mice, chloroform inhibited both spontaneous and ENU-induced liver tumors. When administered in the drinking water, chloroform inhibited, whereas phenobarbital promoted, hepatocarcinogenesis in mice.« less

  9. Is abnormal liver function correlated with food sensitisation in adults? US NHANES, 2005-2006.

    PubMed

    Shiue, I

    2015-01-01

    Associations between liver function and serum IgE levels have recently been observed in children. However, the relationship in adults is unclear. Therefore, it was aimed to study associations of liver function and serum total and food-specific IgE concentrations in a national and population-based study. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006 including demographics, liver status tests, biomarkers, lifestyle factors, and serum total and food-specific IgE concentrations. Participants aged 20 and above were included. Analyses included t-test, chi-square test, and survey-weighted regression modelling. After adjusting for age, sex, ethnicity, vitamin D, waist circumference, family poverty income ratio, total cholesterol, ever asthma, total protein, and survey weighting, abnormal gamma glutamyl transpeptidase was significantly associated with food sensitisation (peanut: OR 2.17, 95%CI 1.60-2.94, P<0.001; egg: OR 2.55, 95%CI 1.32-4.90, P=0.008; milk: OR 2.59, 95%CI 1.56-4.31, P=0.001; shrimp: OR 1.81, 95%CI 1.29-2.55, P=0.002). Moreover, both abnormal albumin and alanine transaminase were associated with egg sensitisation (OR 1.96, 95%CI 1.12-3.43, P=0.022 and OR 2.06, 95%CI 1.04-4.09, P=0.040, respectively). Abnormal liver status tests were correlated with serum food-specific IgE concentrations in adults. Future research with longitudinal design or in clinical settings may be warranted confirming or refuting the observations made in the present epidemiological study. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  10. Protective effects of Urtica dioica seed extract in aflatoxicosis: histopathological and biochemical findings.

    PubMed

    Uyar, A; Yener, Z; Dogan, A

    2016-04-01

    The ameliorative potential and antioxidant capacity of an extract of Urtica dioica seeds (UDS) was investigated using histopathological changes in liver and kidney, measuring serum marker enzymes, antioxidant defence systems and lipid peroxidation (malondialdehyde (MDA)) content in various tissues of broilers exposed to aflatoxin (AF). A total of 32 broilers were divided randomly into 4 groups: control, UDS extract-treated, AF-treated and AF+UDS extract-treated. Broilers in control and UDS extract-treated groups were fed on a diet without AF. The AF-treated group and AF+UDS extract-treated groups were treated with an estimated 1 mg total AF/kg feed. The AF+UDS extract groups received in addition 30 ml UDS extract/kg diet for 21 d. The AF-treated group had significantly decreased body weight gain when compared to the other groups. Biochemical analysis showed a small increase in the concentrations of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and lactate dehydrogenase in the AF-treated group compared to that of the control group, whereas concentrations of these enzymes were decreased in the AF+UDS group compared to that of the AF-treated group. Administration of supplementary UDS extract helped restore the AF-induced increase in MDA and reduced the antioxidant system towards normality, particularly in the liver, brain, kidney and heart. Hepatorenal protection by UDS extracts was further supported by the almost normal histology in AF+UDS extract-treated group as compared to the degenerative changes in the AF-treated broilers. It was concluded that UDS extract has a protective hepatorenal effect in broilers affected by aflatoxicosis, probably acting by promoting the antioxidative defence systems.

  11. Long-term culture and partial characterization of dog gallbladder epithelial cells

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

    Oda, D.; Lee, S.P.; Hayashi, A.

    1991-05-01

    We describe the successful isolation and maintenance of primary cultures of dog gallbladder epithelial cells. The surgically removed gallbladder was treated with trypsin/EDTA for 45 minutes and epithelial cells were collected and resuspended in Eagle's minimum essential medium with 10% fetal calf serum, and plated on Vitrogen-coated culture dishes. Each gallbladder yielded approximately 12 to 15 x 10{sup 6} columnar epithelial cells, greater than 95% of which were viable by trypan blue exclusion. In culture, cells maintained their polarity. They were arranged and grew in small and tight clusters that coalesced at confluency. When examined using transmission electron microscopy, prominentmore » and numerous microville were identified on the apical portion of the plasma membrane. Cells were connected by well-formed desmosomes. Scanning electron microscopy revealed clusters of polyhedral cells with numerous papillary projections. Immunohistochemical studies demonstrated uniform staining of cells to keratin 35BH11 and AE1. Histochemical studies were positive for gamma-glutamyl transpeptidase and negative for glucose-6-phosphatase and albumin. Cells incorporated ({sup 3}H)uridine into intracellular proteins and ({sup 14}C)glucosamine into tissue and secreted mucous glycoproteins linearly over 2 to 24 hours. Flow cytometry studies demonstrated a consistent and reproducible number of cells (10 to 12%) at S-phase. However, the number of cells at S-phase was dramatically reduced to almost negligible as cells reached confluency. This method of culturing primary dog gallbladder epithelial cells is highly reproducible and reliable. These cells preserve their state of differentiation, polarity, histochemical and immunohistochemical profile, morphologic, and metabolic integrity with repeated passaging or after being frozen.« less

  12. Physical activity as a protective factor for development of non-alcoholic fatty liver in men

    PubMed Central

    Pinto, Carla Giuliano de Sá; Marega, Marcio; de Carvalho, José Antonio Maluf; Carmona, Felipe Gambetta; Lopes, Carlos Eduardo Felix; Ceschini, Fabio Luis; Bocalini, Danilo Sales; Figueira, Aylton José

    2015-01-01

    Objective To determine the impact of physical activity on the prevalence of fatty liver, metabolic and cardiovascular disease in adult men. Methods This study evaluated 1,399 men (40.7±8.18 years) with body mass index of 26.7kg/m2 (±3.4) who participated in the Protocol of Preventive Health Check-up at Hospital Israelita Albert Einstein from January to October 2011. We conducted tests of serum blood glucose, total cholesterol, LDL, HDL, triglycerides, reactive c-protein, aspartate transaminase, alanine transaminase and gamma-glutamyl transpeptidase. The statistical analysis comprised in the comparison of mean and standard deviation. The analysis of variance was based in two paths of two way ANOVA, Student’s t-test, Mann Whitney U test, Wald test and χ2. We considered a significance level at p<0.05 and correlation of univariate Poison with 95% confidence interval. Results :Fatty liver was diagnosed in 37.0% of the sample. Triglyceride levels of active men with fatty liver were 148.2±77.6mg/dL while inactive men with fatty liver had 173.4±15.6mg/dL. The remaining serum levels were normal. Inactive individuals showed higher values than active. In addition, inactive individuals have 10.68 times higher risk of developing fatty liver compared with active. Conclusion Physical activity improves metabolic parameters such as triglycerides, weight control, HDL, which interfere in the development of fatty liver. Physically active individuals had lower fatty liver prevalence regardless of values of body composition and lipid profile, leading the conclusion that physical activity has a protective role against development of fatty liver. PMID:25993066

  13. A thin-layer liquid culture technique for the growth of Helicobacter pylori.

    PubMed

    Joo, Jung-Soo; Park, Kyung-Chul; Song, Jae-Young; Kim, Dong-Hyun; Lee, Kyung-Ja; Kwon, Young-Cheol; Kim, Jung-Min; Kim, Kyung-Mi; Youn, Hee-Shang; Kang, Hyung-Lyun; Baik, Seung-Chul; Lee, Woo-Kon; Cho, Myung-Je; Rhee, Kwang-Ho

    2010-08-01

    Several attempts have been successful in liquid cultivation of Helicobaccter pylori. However, there is a need to improve the growth of H. pylori in liquid media in order to get affluent growth and a simple approach for examining bacterial properties. We introduce here a thin-layer liquid culture technique for the growth of H. pylori. A thin-layer liquid culture system was established by adding liquid media to a 90-mm diameter Petri dish. Optimal conditions for bacterial growth were investigated and then viability, growth curve, and released proteins were examined. Maximal growth of H. pylori was obtained by adding 3 mL of brucella broth supplemented with 10% horse to a Petri dish. H. pylori grew in both DMEM and RPMI-1640 supplemented with 10% fetal bovine serum and 0.5% yeast extract. Serum-free RPMI-1640 supported the growth of H. pylori when supplemented with dimethyl-beta-cyclodextrin (200 microg/mL) and 1% yeast extract. Under optimal growth, H. pylori grew exponentially for 28 hours, reaching a density of 3.4 OD(600) with a generation time of 3.3 hours. After 24 hours, cultures at a cell density of 1.0 OD(600) contained 1.3 +/- 0.1 x 10(9 )CFU/mL. gamma-Glutamyl transpeptidase, nuclease, superoxide dismutase, and urease were not detected in culture supernatants at 24 hours in thin-layer liquid culture, but were present at 48 hours, whereas alcohol dehydrogenase, alkylhydroperoxide reductase, catalase, and vacuolating cytotoxin were detected at 24 hours. Thin-layer liquid culture technique is feasible, and can serve as a versatile liquid culture technique for investigating bacterial properties of H. pylori.

  14. Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury.

    PubMed

    Barbonetti, Arcangelo; Caterina Vassallo, Maria Rosaria; Cotugno, Michele; Felzani, Giorgio; Francavilla, Sandro; Francavilla, Felice

    2016-07-01

    Non-alcoholic fatty liver disease (NAFLD) has been claimed as a liver phenotype of metabolic syndrome, which in turn is associated with male hypogonadism. We assessed whether an independent association between NAFLD and androgen deficiency could be revealed in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of biochemical androgen deficiency and a combination of risk factors for metabolic syndrome. Fifty-five consecutive men with chronic SCI admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography. NAFLD was diagnosed in 27 patients (49.1%). Men with NAFLD were older and exhibited significantly higher body mass index, Homeostatic model assessment of insulin resistance, triglycerides and gamma-glutamyl transpeptidase values, lower total and free testosterone levels and they were engaged in a significantly poorer weekly leisure time physical activity (LTPA). At the multiple logistic regression analysis, only total and free testosterone levels exhibited a significant independent association with NAFLD. The risk of having NAFLD increased indeed of 1% for each decrement of 1 ng/dL of total testosterone and of 3% for each decrement of 1 pg/mL of free testosterone, after adjustment for confounders. In men with total testosterone < 300 ng/dL (36.4%) the prevalence of NAFLD reached 85%: they had a risk of having NAFLD significantly higher (∼12-fold) than those with total testosterone ≥ 300 ng/dL, after adjustment for confounders. The evidence of an independent association between NAFLD and low testosterone is strongly reinforced by its demonstration in men with chronic SCI, in spite of the many confounders peculiar to this population.

  15. Premature hair whitening is an independent predictor of carotid intima-media thickness in young and middle-aged men.

    PubMed

    Erdoğan, Turan; Kocaman, Sinan Altan; Çetin, Mustafa; Durakoğlugil, Murtaza Emre; Uğurlu, Yavuz; Şahin, İsmail; Çanga, Aytun

    2013-01-01

    Premature graying or whitening of the hair may possibly represent premature atherosclerotic changes as a surrogate marker of different host responses to cardiovascular risk factors (CVRFs). This study was undertaken to test whether carotid artery intima-media thickness (CIMT) as a validated surrogate marker of the severity and extent of coronary artery disease (CAD) is higher in subjects with prominent signs of hair whitening, independent of chronological age and other CVRFs. The current study was conducted in young and middle-aged patients (<55 years age) without a history of cardiovascular disease. Two hundred and two eligible patients consecutively admitted to our outpatient clinic for CVRF management were included. A gray/white-hair scale was used to determine the percentage of hair whitening. In the groups determined according to the degree of hair whitening, age (p<0.001), waist circumference (p=0.011), the presence of hypertension (p=0.003), the uric acid levels (p=0.008), the C - reactive protein levels (p=0.002) and CIMT (p<0.001) were significantly different. When we performed multivariate analyses to determine the independent predictors of CIMT and hair whitening, CIMT was found to be related to age, waist circumference, the levels of uric acid, bilirubin and gamma-glutamyl transpeptidase, the presence of a family history of CAD and hair whitening, while hair whitening was found to be related to age, hypertension, the bilirubin level and CIMT. Our findings suggest that premature hair whitening intensity is independently related to CIMT. In cumulative assessments of CVRFs on the human body, the presence of premature hair whitening may be useful in identifying individuals with an increased risk of cardiovascular disease.

  16. Meta-analysis of structured triglyceride versus other lipid emulsions for parenteral nutrition.

    PubMed

    Zhu, Mengbai; Li, Xueliang

    2013-06-01

    Structured triglyceride (STG) is a new emulsion synthesized from long-chain fatty acids and medium-chain fatty acids bound to the same glycerol backbone. We performed a meta-analysis to examine the safety, efficacy, and tolerability of STG for parenteral nutrition. We searched MEDLINE, EMBASE, and the Chinese Biomedicine Database, with the last search done in May 2012. Only randomized controlled trials in humans published in Chinese or English were included. Search terms included structured triglyceride and structural lipid. Methodologic quality was evaluated using the Jadad Scale. Meta-analysis was conducted using Review Manager 5.0.24 to calculate the weighted mean difference (WMD) and standardized mean difference (SMD) with 95% confidence intervals. Twenty-one studies (833 participants) published in English or Chinese were included in the analysis. STG significantly affected plasma triglycerides (WMD = -0.15; 95% confidence interval [CI], -0.29 to -0.01; P = 0.04), plasma glycerol (WMD = 0.21; 95% CI, 0.01-0.41; P = 0.04), free fatty acids (WMD = 0.21; 95% CI, 0.03-0.39; P = 0.02), nitrogen balance (SMD = 1.13; 95% CI, 0.26-1.99; P = 0.01), AST (WMD = -5.97; 95% CI, -7.17 to -4.76; P < 0.00001), and glucose (WMD = -0.18; 95% CI, -0.30 to -0.06; P = 004), but not respiratory quotient, resting energy expenditure, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin, cholesterol, serum creatinine, or vital signs. STG is rapidly metabolized without harming the liver, and positively affects nitrogen balance. STG is at least as safe and effective for parenteral nutrition as other triglycerides. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children--a technical report.

    PubMed

    Beez, Thomas; Sarikaya-Seiwert, Sevgi; Steiger, Hans-Jakob; Hänggi, Daniel

    2014-03-01

    5-aminolevulinic acid (5-ALA) can be used as an adjunct for the surgery of adult malignant glioma and improves the rate of gross total resection and patient survival. So far, only three casuistic reports of fluorescence-guided surgery used in children have been published. We report our pilot series of 16 pediatric brain tumors treated with 5-ALA. Sixteen patients (mean age 9 years, range 1-16 years) received a standardized 5-ALA dose according to the published protocol after informed parental consent. The fluorescence status (positive versus negative) in correlation with histology as well as blood samples and adverse clinical symptoms were recorded. Histology revealed pilocytic astrocytoma (n = 7), classical medulloblastoma (n = 4), anaplastic astrocytoma (n = 1), glioblastoma (n = 3) and anaplastic ependymoma (n = 1). Positive fluorescence was observed in cases of anaplastic astrocytoma, glioblastoma, and medulloblastoma, respectively. Significant increases were registered for alanine aminotransferase (14.92 ± 1.106 U/l vs. 37.70 ± 3.795 U/l, P = 0.0020) and gamma glutamyl transpeptidase (12.69 ± 1.638 U/l vs. 39.29 ± 6.342 U/l, P = 0.0156), correlated with young age. No further adverse reactions were evident. Positive fluorescence was observed in two high-grade gliomas and one medulloblastoma after oral administration of 5-ALA. Thus, 5-ALA appears capable of inducing fluorescence in pediatric high-grade tumors. Adverse reactions observed in children were similar to those reported for adults, although very young children might be at increased risk. Further studies are required to elucidate pharmacokinetic and pharmacodynamic properties of 5-ALA in children and to assess its prognostic role in the resection of pediatric brain tumors.

  18. A cross-sectional study of the relationship between serum liver enzymes level and the incidence of impaired fasting glucose in males and females.

    PubMed

    Qin, Guangming; Lu, Lihong; Xiao, Yufei; Zhu, Yimiao; Pan, Wensheng; Xu, Xiang; Shen, Shengrong; Das, Undurti N

    2014-07-28

    The aim of this study was to investigate the possible correlation between levels of serum liver enzymes and impaired fasting glucose (IFG) in Chinese adults and to provide a new perspective for the prevention of pre-diabetes. Serum liver enzymes of the samples including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and g-glutamyl transferase (GGT), as well as plasma glucose, blood lipids, and insulin, were measured. The cumulative incidences of IFG between different quartiles of liver enzymes were compared by the chi-square test. A logistic regression model (binary regression) was used to calculate the odds ratio (OR) of IFG with 95% confidence interval (95% CI). The total incidence of IFG was 20.3% and the cumulative incidence of IFG was higher in men compared to women. In both sexes, IFG is more prevalent in higher quartiles of liver enzymes. After adjusting for age, BMI, blood pressure, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), the cumulative incidences of IFG were significantly higher in the highest quartiles of liver enzymes than in the lowest quartiles. A significantly higher cumulative incidence of IFG was found in the highest GGT quartile than in the lowest quartile for woman. The results of this study suggest that serum liver enzymes are related to the risk of IFG in Chinese adults. We infer that preserving the hepatic function may be an efficient way to prevent the development of IFG, especially in males.

  19. Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

    PubMed Central

    Hu, Yan-Chao; Liu, Hao; Liu, Xiao-Yan; Ma, Li-Na; Guan, Yu-Hua; Luo, Xia; Ding, Xiang-Chun

    2017-01-01

    AIM To investigate the value of the gamma-glutamyltraspeptidase (GGT)-to-platelet (PLT) ratio (GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase (AST)-to-PLT ratio index (APRI), and fibrosis-4 (FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin (TBil), alanine aminotransferase (ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic (ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated with CHB patients’ age, gender, or disease duration (P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count (P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis (P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI (F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4

  20. Transpeptidase activity of penicillin-binding protein SpoVD in peptidoglycan synthesis conditionally depends on the disulfide reductase StoA.

    PubMed

    Bukowska-Faniband, Ewa; Hederstedt, Lars

    2017-07-01

    Endospore cortex peptidoglycan synthesis is not required for bacterial growth but essential for endospore heat resistance. It therefore constitutes an amenable system for research on peptidoglycan biogenesis. The Bacillus subtilis sporulation-specific class B penicillin-binding protein (PBP) SpoVD and many homologous PBPs contain two conserved cysteine residues of unknown function in the transpeptidase domain - one as residue x in the SxN catalytic site motif and the other in a flexible loop near the catalytic site. A disulfide bond between these residues blocks the function of SpoVD in cortex synthesis. With a combination of experiments with purified proteins and B. subtilis mutant cells, it was shown that in active SpoVD the two cysteine residues most probably interact by hydrogen bonding and that this is important for peptidoglycan synthesis in vivo. It was furthermore demonstrated that the sporulation-specific thiol-disulfide oxidoreductase StoA reduces SpoVD and that requirement of StoA for cortex synthesis can be suppressed by two completely different types of structural alterations in SpoVD. It is concluded that StoA plays a critical role mainly during maturation of SpoVD in the forespore outer membrane. The findings advance our understanding of essential PBPs and redox control of extra-cytoplasmic protein disulfides in bacterial cells. © 2017 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.

  1. Anticonvulsant properties of alpha, gamma, and alpha, gamma-substituted gamma-butyrolactones.

    PubMed

    Klunk, W E; Covey, D F; Ferrendelli, J A

    1982-09-01

    Derivatives of gamma-butyrolactone (GBL) substituted on the alpha- and/or gamma-positions were synthesized and tested for their effects on behavior in mice, on the electroencephalographs and blood pressure of paralyzed-ventilated guinea pigs, and on electrical activity of incubated hippocampal slices. Several compounds, including alpha-ethyl-alpha-methyl GBL (alpha-EMGBL), alpha, alpha-dimethyl GBL, alpha, gamma-diethyl-alpha, gamma-dimethyl GBL, and gamma-ethyl-gamma-methyl GBL, prevented seizures induced by pentylenetetrazol, beta-ethyl-beta-methyl-gamma-butyrolactone (beta-EMGBL), picrotoxin, or all three compounds in mice and guinea pigs but had no effect on seizures induced by maximal electroshock or bicuculline. Neither gamma-hydroxybutyrate (GHB) nor alpha-isopropylidine GBL had any anticonvulsant activity. The anticonvulsant alpha-substituted compounds had a potent hypotensive effect and antagonized the hypertensive effect of beta-EMGBL, alpha-EMGBL was tested in incubated hippocampal slices and was found to depress basal activity and antagonize excitation induced by beta-EMGBL. These results demonstrate that alpha-alkyl-substituted GBL and, to a lesser extent, gamma-substituted derivatives are anticonvulsant agents and that their effects are strikingly different from those of GHB or beta-alkyl-substituted GBLs, which are epileptogenic. Possibly beta- and alpha-substituted GBLs act at the same site as agonists and antagonists, respectively.

  2. Histopathological and biochemical investigations of protective role of honey in rats with experimental aflatoxicosis.

    PubMed

    Yaman, Turan; Yener, Zabit; Celik, Ismail

    2016-07-21

    Natural honey (honey) is considered as a part of traditional medicine all over the world. It has both antimicrobial and antioxidant properties, useful in stimulation of wounds and burns healing and gastric ulcers treatment. The aim of this study, for the first time, was to investigate the antioxidant properties and protective role of honey against carcinogen chemical aflatoxin (AF) exposure in rats, which were evaluated by histopathological changes in liver and kidney, measuring level of serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), gamma glutamil transpeptidase (GGT)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)], and lipid peroxidation content in liver, erythrocyte, brain, kidney, heart and lungs. Eighteen healthy Sprague-Dawley rats were randomly allocated into three experimental groups: A (Control), B (AF-treated) and C (AF + honey-treated). While rats in group A were fed with a diet without AF, B, and C groups received 25 μg of AF/rat/day, where C group additionally received 1 mL/kg of honey by gavage for 90 days. At the end of the 90-day experimental period, we found that the honey supplementation decreased the lipid peroxidation and the levels of enzyme associated with liver damage, increased enzymatic and non-enzymatic antioxidants in the AF + honey-treated rats. Hepatoprotective and nephroprotective effects of honey is further substantiated by showing almost normal histological architecture in AF + honey-treated group, compared to degenerative changes in the liver and kidney of AF-treated rats. Additionally, honey supplementation ameliorated antioxidant defens systems and lipid peroxidation in content in other tissues of AF + honey treated rats. The present study indicates that honey has a hepatoprotective and nephroprotective effect in rats with experimental aflatoxicosis due to

  3. Boar seminal plasma components and their relation with semen quality.

    PubMed

    López Rodríguez, Alfonso; Rijsselaere, Tom; Beek, Josine; Vyt, Philip; Van Soom, Ann; Maes, Dominiek

    2013-02-01

    Select boar seminal plasma (SP) components and their relation to semen quality were investigated. Thirty nine boars from three artificial insemination (AI) centers were divided into group A (GA: > 80% normal sperm and >70% motility) and group B (GB: < 80% normal sperm and < 70% motility). Each ejaculate was collected and semen volume, concentration, sperm motility (computer aided semen analysis; CASA), morphology, and vitality (both eosin nigrosin staining) were investigated. The SP was separated and analyzed for aspartate-amino-transferase (AST), γ-glutamyl-transferase (GGT), alkaline phosphatase (ALP) activity, and the concentrations of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), phosphate (PO(4)(3-)), magnesium (Mg), selenium (Se) and zinc (Zn) were assessed. Repeated measures (2 months interval) were conducted in eight boars of GA from one AI center. The activity of GGT (r = -0.482) and ALP (r = -0.459) was moderately associated (p < 0.05) with ejaculate volume and strongly associated with concentration (r = 0.580 and r = 0.618, respectively; p = 0.000). Moderate associations (p < 0.05) were found between ALP (r = 0.439), GGT (r = 0.387), Na (r = -0.428), K (r = 0.354), and Se (r = 0.354) with progressive motility. The SP concentration of Na (r = -0.401), Cl (r = -0.521), and K (r = 0.350) was associated (p < 0.05) with normal morphology. Only Mg was associated (p < 0.05) with membrane damage (r = -0.335). The concentration of Na, Cl, and Zn (1681.0 vs. 1701.0 µg/dL) was different between groups (p < 0.05). Repeated measures showed significant differences in time but only for Na, Mg, and Zn (p < 0.05). In conclusion, several biochemical components of SP were related to semen quality. The analysis of biochemical parameters could provide extra information about reproductive health of AI boars.

  4. What determines human body odour?

    PubMed

    Hamada, Kaoru; Haruyama, Sanehito; Yamaguchi, Takashi; Yamamoto, Kayo; Hiromasa, Kana; Yoshioka, Manabu; Nishio, Daisuke; Nakamura, Motonobu

    2014-05-01

    Human body odour and earwax type are genetically dependent on a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. So far, it still remains to be clear how SNP in the ABCC11 gene is associated with human malodour. In a recent issue of Experimental Dermatology, Baumann et al. propose one of the underlying molecular pathways. Although one of the amino acid conjugated of the odorants, Cys-Gly-3-methyl-3-sulfanylhexanol (3M3SH), was not taken up by the transporter ABCC11, glutathione conjugate of 3MSH (SG-3MSH) was transported by ABCC11. Moreover, SG-3MSH was processed to 3M3SH by γ-glutamyl-transferase 1 (GGT1), which was abundantly expressed in apocrine sweat glands. These findings may pave a way for the pharmacogenetics of human body odour and the development of innovative deodorant products. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Uptake and speciation of selenium in garlic cultivated in soil amended with symbiotic fungi (mycorrhiza) and selenate.

    PubMed

    Larsen, Erik H; Lobinski, Ryszard; Burger-Meÿer, Karin; Hansen, Marianne; Ruzik, Rafal; Mazurowska, Lena; Rasmussen, Peter Have; Sloth, Jens J; Scholten, Olga; Kik, Chris

    2006-07-01

    The scope of the work was to investigate the influence of selenate fertilisation and the addition of symbiotic fungi (mycorrhiza) to soil on selenium and selenium species concentrations in garlic. The selenium species were extracted from garlic cultivated in experimental plots by proteolytic enzymes, which ensured liberation of selenium species contained in peptides or proteins. Separate extractions using an aqueous solution of enzyme-deactivating hydroxylamine hydrochloride counteracted the possible degradation of labile selenium species by enzymes (such as alliinase) that occur naturally in garlic. The selenium content in garlic, which was analysed by ICP-MS, showed that addition of mycorrhiza to the natural soil increased the selenium uptake by garlic tenfold to 15 microg g(-1) (dry mass). Fertilisation with selenate and addition of mycorrhiza strongly increased the selenium content in garlic to around one part per thousand. The parallel analysis of the sample extracts by cation exchange and reversed-phase HPLC with ICP-MS detection showed that gamma-glutamyl-Se-methyl-selenocysteine amounted to 2/3, whereas methylselenocysteine, selenomethionine and selenate each amounted to a few percent of the total chromatographed selenium in all garlic samples. Se-allyl-selenocysteine and Se-propyl-selenocysteine, which are selenium analogues of biologically active sulfur-containing amino acids known to occur in garlic, were searched for but not detected in any of the extracts. The amendment of soil by mycorrhiza and/or by selenate increased the content of selenium but not the distribution of detected selenium species in garlic. Finally, the use of two-dimensional HPLC (size exclusion followed by reversed-phase) allowed the structural characterisation of gamma-glutamyl-Se-methyl-selenocysteine and gamma-glutamyl-Se-methyl-selenomethionine in isolated chromatographic fractions by quadrupole time-of-flight mass spectrometry.

  6. Evaluation of passive transfer in captive greater kudu (Tragelaphus strepsiceros).

    PubMed

    Hammond, Elizabeth E; Fiorello, Christine V

    2011-12-01

    Failure of passive transfer (FPT) in captive greater kudu (Tragelaphus strepsiceros) calves can lead to increased morbidity and mortality. In this retrospective study, serum samples from neonatal kudu calves were tested for immunoglobulin using different tests validated for domestic ruminants, including measurement of gamma globulin (GG) measured by protein electrophoresis, total solids (TS) measured by calibrated refractometry, total protein (TP) and globulins measured by colorimetry, gamma glutamyltransferase (GGT), and the zinc sulfate turbidity test (ZSTT). In a logistic regression model, TP, TS, globulins, and the natural log transform of GGT were the only significant parameters associated with FPT. Various historic parameters related to the dam, as well as calf weight, sex, glucose, and packed cell volume, were not significant. Based on the results, FPT in greater kudu is defined as GG of < 0.5 g/dl, a value lower than that in domestic cattle. TS measured by refractometry has an 80% sensitivity and a 100% specificity for FPT in greater kudu. With FPT defined as GG < 0.5 g/dl, kudu calves with a TS < 4.8 g/dl and a negative ZSTT have an increased probability of requiring medical intervention and additional diagnostics may be warranted.

  7. CYP2E1 immunoglobulin G4 subclass antibodies after desflurane anesthesia

    PubMed Central

    Batistaki, Chrysanthi; Michalopoulos, George; Matsota, Paraskevi; Nomikos, Tzortzis; Kalimeris, Konstantinos; Riga, Maria; Nakou, Maria; Kostopanagiotou, Georgia

    2014-01-01

    AIM: To investigate CYP2E1 IgG4 autoantibody levels and liver biochemical markers in adult patients after anesthesia with desflurane. METHODS: Forty patients who were > 18 years old and undergoing elective surgery under general anesthesia with desflurane were studied. Alpha-glutathione-S-transferase (αGST) and IgG4 antibodies against CYP2E1 were measured preoperatively and 96 h postoperatively, as well as complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), g-glutamyl-transpeptidase (gGT), alkaline phosphatase, total serum proteins, albumin and bilirubin. A separate group of 8 patients who received regional anesthesia was also studied for calibration of the methodology used for CYP2E1 IgG4 and αGST measurements. Student’s t-test and the Mann-Whitney U test were used for comparison of the continuous variables, and Fisher’s exact test was used for the categorical variables. All tests were two-tailed, with statistical significance set as P < 0.05. RESULTS: None of the patients developed postoperative liver dysfunction, and all patients were successfully discharged from the hospital. No statistically significant difference was observed regarding liver function tests (SGOT, SGPT, γGT, bilirubin, INR), αGST and CYP2E1 IgG4, before and after exposure to desflurane. After dividing patients into two subgroups based on whether or not they had received general anesthesia in the past, no significant difference in the levels of CYP2E1 IgG4 was observed at baseline or 96 h after desflurane administration (P = 0.099 and P = 0.051, respectively). Alpha-GST baseline levels and levels after the intervention also did not differ significantly between these two subgroups (P > 0.1). The mean αGST differences were statistically elevated in men by 2.15 ng/mL compared to women when adjusted for BMI, duration of anesthesia, number of times

  8. Phoenix dactylifera protects against oxidative stress and hepatic injury induced by paracetamol intoxication in rats.

    PubMed

    Salem, Gamal A; Shaban, Ahmed; Diab, Hussain A; Elsaghayer, Wesam A; Mjedib, Manal D; Hnesh, Aomassad M; Sahu, Ravi P

    2018-05-16

    The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group. These PCM-induced effects were associated with oxidative stress as demonstrated by increased levels of malondialdehyde (MDA) and reduced levels of hepatic antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Pretreatment of PLME decreased ALT and AST by 78.2% and tissue MDA by 54.1%, and increased hepatic GPx (3.5 folds), CAT (7 folds) and SOD (2.5 folds) compared to PCM group. These PLME-mediated effects were comparable to NAC pretreatment. Histological analysis demonstrates that PLME conserved hepatic tissues against lesions such as inflammation, centrilobular necrosis, and hemorrhages induced by PCM. In contrast, PLAE-mediated effects were less effective in reducing levels of liver function enzymes, oxidative stress, and liver histopathological profiles, and restoring antioxidant defenses against PCM-induced intoxication. These findings indicate that PLME exerts protective effects against PCM-induced hepatotoxicity via scavenging free radicals and restoring hepatic antioxidant enzymes. Thus, PLME and its bioactive components could further be evaluated for their pharmacological properties against drug-induced deleterious effects. Copyright © 2018. Published by Elsevier Masson SAS.

  9. Therapeutic role of Cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity.

    PubMed

    Aruna, K; Rukkumani, R; Varma, P Suresh; Menon, Venugopal P

    2005-05-01

    Ethanol is one of the most widely used and abused drugs, increasing lipid levels in humans and experimental animals. Heating of oil rich in polyunsaturated fatty acids (PUFA) produces various lipid peroxidative end products that can aggravate the pathological changes produced by ethanol. In the present communication, the effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced hyperlipidaemia. The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of rats given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in rats groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats. The levels were decreased when cumin was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of groups given alcohol, thermally oxidized oil and alcohol+thermally oridized oil when compared with the normal control rats. The level increased when cumin was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats, whereas the activity was decreased with the cumin treatment. The results obtained indicate that cumin can decrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity. Copyright (c) 2005 John Wiley & Sons, Ltd.

  10. Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality.

    PubMed

    Ulmer, Hanno; Kelleher, Cecily; Diem, Günter; Concin, Hans

    2004-01-01

    To assess the impact of sex-specific patterns in cholesterol levels on all-cause and cardiovascular mortality in the Vorarlberg Health Monitoring and Promotion Programme (VHM&PP). In this study, 67413 men and 82237 women (aged 20-95 years) underwent 454448 standardized examinations, which included measures of blood pressure, height, weight, and fasting samples for cholesterol, triglycerides, gamma-glutamyl transferase (GGT), and glucose in the 15-year period 1985-1999. Relations between these variables and risk of death were analyzed using two approaches of multivariate analyses (Cox proportional hazard and GEE models). Patterns of cholesterol levels showed marked differences between men and women in relation to age and cause of death. The role of high cholesterol in predicting death from coronary heart disease could be confirmed in men of all ages and in women under the age of 50. In men, across the entire age range, although of borderline significance under the age of 50, and in women from the age of 50 onward only, low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases. Triglycerides > 200 mg/dl had an effect in women 65 years and older but not in men. This large-scale population-based study clearly demonstrates the contrasting patterns of cholesterol level in relation to risk, particularly among those less well studied previously, that is, women of all ages and younger people of both sexes. For the first time, we demonstrate that the low cholesterol effect occurs even among younger respondents, contradicting the previous assessments among cohorts of older people that this is a proxy or marker for frailty occurring with age.

  11. Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

    PubMed Central

    Longo-Mbenza, Benjamin; Mvitu Muaka, Moise; Masamba, Wayiza; Muizila Kini, Lucien; Longo Phemba, Igor; Kibokela Ndembe, Dalida; Tulomba Mona, Doris

    2014-01-01

    AIM To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. METHODS We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). RESULTS The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. CONCLUSION Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM. PMID:24790873

  12. Formation of 5-Oxoproline from Glutathione in Erythrocytes by the γ-Glutamyltranspeptidase-Cyclotransferase Pathway

    PubMed Central

    Palekar, Anil G.; Tate, Suresh S.; Meister, Alton

    1974-01-01

    γ-Glutamyltranspeptidase activity was demonstrated in the membrane fraction of rabbit erythrocytes. The activity observed (with glutathione and various amino-acid acceptors) was similar in magnitude to that of the γ-glutamylcyclotransferase and γ-glutamylcysteine synthetase activities found in the soluble fraction of the cell. No transpeptidase activity was observed with either γ-glutamyl p-nitroanilide or oxidized glutathione in contrast to the rabbit-kidney enzyme for which these compounds and glutathione serve as substrates. Erythrocyte suspensions and hemolysates formed 5-oxoproline (pyroglutamate; pyrrolidone carboxylate); the rate of 5-oxoproline formation from glutathione by hemolysates was increased by addition of methionine. The findings indicate that 5-oxoproline is an end-product of glutathione metabolism in erythrocytes, and that 5-oxoproline passes out of the erythrocyte and is metabolized in other tissues. The observed rate of 5-oxoproline formation is consistent with the conclusion that the γ-glutamyltranspeptidase-cyclotransferase pathway, together with the synthesis of glutathione from glycine, cysteine, and glutamate, account for a large fraction of the observed amino-acid turnover of erythrocyte glutathione. PMID:4150022

  13. Immune responses to Helicobacter pylori infection

    PubMed Central

    Moyat, Mati; Velin, Dominique

    2014-01-01

    Helicobacter pylori (H. pylori) infection is one of the most common infections in human beings worldwide. H. pylori express lipopolysaccharides and flagellin that do not activate efficiently Toll-like receptors and express dedicated effectors, such as γ-glutamyl transpeptidase, vacuolating cytotoxin (vacA), arginase, that actively induce tolerogenic signals. In this perspective, H. pylori can be considered as a commensal bacteria belonging to the stomach microbiota. However, when present in the stomach, H. pylori reduce the overall diversity of the gastric microbiota and promote gastric inflammation by inducing Nod1-dependent pro-inflammatory program and by activating neutrophils through the production of a neutrophil activating protein. The maintenance of a chronic inflammation in the gastric mucosa and the direct action of virulence factors (vacA and cytotoxin-associated gene A) confer pro-carcinogenic activities to H. pylori. Hence, H. pylori cannot be considered as symbiotic bacteria but rather as part of the pathobiont. The development of a H. pylori vaccine will bring health benefits for individuals infected with antibiotic resistant H. pylori strains and population of underdeveloped countries. PMID:24914318

  14. Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A]: An Unstable Hemoglobin Newly Detected as a De Novo Mutation in a Mauritanian Patient.

    PubMed

    Ghaber, Sidi M; Trabelsi, Nawel; Salem, Mohamed L; Haddad, Faten; Abba, Aminetou; Darragi, Imen; Abbes, Salem

    2018-01-01

    Unstable hemoglobins (Hbs) are a group of Hb disorders that could be the origin of chronic hemolytic anemia. Most of these disorders are caused by point mutations taking place in the globin genes and affecting the stability of the Hb molecule. They are inherited as autosomal dominant diseases and described worldwide. Herein we report a new observation of an unstable variant in the Mauritanian population. The patient was a young girl of Mauritanian origin. She presented with chronic hemolytic anemia with an unknown etiology after being referred to several medical centers. Laboratory investigations based on routine analyses, capillary electrophoresis (CE), cation exchange high performance liquid chromatography (HPLC) and DNA sequencing revealed an abnormal unstable Hb known as Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A] that occurred as a de novo mutation newly detected in an African girl of Mauritanian origin.

  15. Elevated Apoptosis in the Liver of Dairy Cows with Ketosis.

    PubMed

    Du, Xiliang; Chen, Liang; Huang, Dan; Peng, Zhicheng; Zhao, Chenxu; Zhang, Yuming; Zhu, Yiwei; Wang, Zhe; Li, Xinwei; Liu, Guowen

    2017-01-01

    Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively. Liver histology, TUNEL and Oil red O staining were performed in liver tissue samples. TG contents were measured using an enzymatic kit; Caspase 3 assays were carried out using the Caspase 3 activity assay kit; oxidation and antioxidant markers were measured using biochemical kits; apoptosis pathway were determined by qRT-PCR and western blot. Ketotic cows displayed hepatic fat accumulation. The hepatic malondialdehyde (MDA) content was significantly increased, but the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were markedly decreased in ketotic cows compared with control cows, indicating that ketotic cows displayed severe oxidative stress. Significantly higher serum levels of the hepatic damage markers AST, ALT, GGT and GLDH were observed in ketotic cows than in control cows. The blood concentration of the apoptotic marker CK18 M30 and the number of TUNEL-positive cells in the liver of ketotic cows were 1.19- and 2.61-fold, respectively, higher than the values observed in control cows. Besides, Caspase 3 activity was significantly increased in the liver of ketosis cows. Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) was markedly decreased, which

  16. The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study.

    PubMed

    Kim, Sang-Wook; Ha, Ki-Chan; Choi, Eun-Kyung; Jung, Su-Young; Kim, Min-Gul; Kwon, Dae-Young; Yang, Hye-Jung; Kim, Min-Jung; Kang, Hee-Joo; Back, Hyang-Im; Kim, Sun-Young; Park, Soo-Hyun; Baek, Hum-Young; Kim, Yong-Jae; Lee, Joon-Yeol; Chae, Soo-Wan

    2013-03-08

    Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the

  17. Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial.

    PubMed

    Buchman, A L; Ament, M E; Sohel, M; Dubin, M; Jenden, D J; Roch, M; Pownall, H; Farley, W; Awal, M; Ahn, C

    2001-01-01

    Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0

  18. Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: a systematic review and meta-analysis.

    PubMed

    Khalesi, Saman; Johnson, David Wayne; Campbell, Katrin; Williams, Susan; Fenning, Andrew; Saluja, Sonia; Irwin, Christopher

    2017-11-08

    The gut-liver interaction suggests that modification of gut bacterial flora using probiotics and synbiotics may improve liver function. This systematic review and meta-analysis aimed to clarify the effect of probiotics and synbiotics consumption on the serum concentration of liver function enzymes. PubMed (MEDLINE), Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library (Central) were searched from 1980 to August 2017 for studies where adults consumed probiotics and/or synbiotics in controlled trials and changes in liver function enzymes were examined. A total of 17 studies (19 trials) were included in the meta-analysis. Random effects meta-analyses were applied. Probiotics and synbiotics significantly reduced serum alanine aminotransferase [- 8.05 IU/L, 95% confidence interval (CI) - 13.07 to - 3.04; p = 0.002]; aspartate aminotransferase (- 7.79 IU/L, 95% CI: - 13.93 to - 1.65; p = 0.02) and gamma-glutamyl transpeptidase (- 8.40 IU/L, 95% CI - 12.61 to - 4.20; p < 0.001). Changes in the serum concentration of alkaline phosphatase and albumin did not reach a statistically significant level. Changes to bilirubin levels were in favour of the control group (0.95 μmol/L, 95% CI 0.48-1.42; p < 0.001). Subgroup analysis suggested the existence of liver disease at baseline, synbiotics supplementation and duration of supplementation ≥ 8 weeks resulted in more pronounced improvement in liver function enzymes than their counterparts. Probiotics and synbiotics may be suggested as supplements to improve serum concentration of liver enzymes, especially when synbiotics administered for a period ≥ 8 weeks and in individuals with liver disease.

  19. Evaluation of ameliorative effect of curcumin on imidacloprid-induced male reproductive toxicity in wistar rats.

    PubMed

    Lonare, Milindmitra; Kumar, Manoj; Raut, Sachin; More, Amar; Doltade, Sagar; Badgujar, Prarabdh; Telang, Avinash

    2016-10-01

    This study was undertaken to investigate the toxic effects of imidacloprid (IM) on male reproductive system and ameliorative effect of curcumin (CMN) in male Wistar rats. For this purpose, IM (45 and 90 mg/kg, body weight) and CMN (100 mg/kg, body weight) were administered orally to the rats either alone or in combinations for a period of 28 days. At the end of experiment, male reproductive toxicity parameters (total sperm count and sperm abnormalities), testosterone level, steroidal enzymatic activity [3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD], and oxidative stress indicators were estimated in testis and plasma. IM treatments resulted in significant decrease (p < 0.05) in total epididymal sperm count, sperm motility, live sperm count, and increase (p < 0.05) in sperm abnormalities. Activities of gamma-glutamyl transpeptidase, lactate dehydrogenase-x, and sorbitol dehydrogenase were significantly increased (p < 0.05), while, 3β-HSD and 17β-HSD enzymatic activity along with testosterone concentration in testis and plasma were decreased significantly (p < 0.05) in IM-treated rats. IM exposure resulted in significant increase (p < 0.05) in LPO and decrease (p < 0.05) in GSH level along with decreased activities of CAT, SOD, GPx, and GST. IM-treated rats showed histopathological alterations in testis and epididymis. However, the reproductive toxicity parameters, oxidative stress indicators, and histopathological changes were minimized and functional restorations were noticed by co-administration of CMN in IM-treated rats. The results of this study suggest that IM-induced male reproductive toxic effects could be ameliorated by CMN supplementation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1250-1263, 2016. © 2015 Wiley Periodicals, Inc.

  20. The diagnostic value of a globulin/platelet model for evaluating liver fibrosis in chronic hepatitis B patients.

    PubMed

    Coskun, Banu Demet; Altinkaya, Engin; Sevinc, Eylem; Ozen, Mustafa; Karaman, Hatice; Karaman, Ahmet; Poyrazoglu, Orhan

    2015-12-01

    Liver biopsy, which is considered the best method for evaluating hepatic fibrosis, has important adverse events. Therefore, non-invasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis B. To verify the usefulness of a new fibrosis index the globulin/platelet model in patients with chronic hepatitis B and to compare it with other noninvasive tests for predicting significant fibrosis. This study was the second to evaluate the globulin/platelet model in HBV patients. We retrospectively investigated 228 patients with chronic hepatitis B who performed liver biopsy from 2013 to 2014. The globulin/platelet model, APGA [AST/Platelet/Gamma-glutamyl transpeptidase/Alfa-fetoprotein], FIB4, fibrosis index, cirrhosis discriminate score, and Fibro-quotient were calculated, and the diagnostic accuracies of all of the fibrosis indices were compared between the F0-2 (no-mild fibrosis) and F3-6 (significant fibrosis) groups. All of the noninvasive markers were significantly correlated with the stage of liver fibrosis (p < 0,001). To predict significant fibrosis (F ≥ 3), the area under the curve (95% CI) was found to be greatest for APGA (0.83 [0.74-0.86]), followed by FIB-4 (0.75[0.69-0.80]), the globulin/platelet model (0.74 [0.68-0.79]), fibrosis index (0.72 [0.6-0.78], cirrhosis discriminate score (0.71 [0.64-0.76]) and Fibro-quotient (0.62 [0.55-0.7]). The area under the receiver operating characteristic curves of APGA was significantly higher than that of the other noninvasive fibrosis markers (p < 0.05). While the APGA index was found to be the most valuable test for the prediction significant fibrosis in patients with chronic hepatitis B, GP model was the thirth valuable test. Therefore, we recommended that APGA could be used instead of the GP model for prediction liver fibrosis.

  1. Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function.

    PubMed

    Kołodziejski, Paweł A; Pruszyńska-Oszmałek, Ewa; Strowski, Mathias Z; Nowak, Krzysztof W

    2017-06-01

    Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover, obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus.

  2. [Helicobacter pylori -- 2010].

    PubMed

    Buzás, György Miklós

    2010-12-05

    Helicobacter pylori, discovered 27 years ago, has remained the most prevalent infectious agent in the world. In the author's hypothesis, the increase of peptic ulcer prevalence in the 19-20th century could be attributable to the extended worldwide use of gastric tubes for secretory testing which led to the iatrogenic transmission of pathogenic strains. Helicobacter pylori outer membrane proteins (OMP), and duodenal ulcer promoting (dupA) proteins were identified as novel virulence factors, leading to the production of pro-inflammatory cytokines, which could be future targets of therapy. There is no ideal first-line eradication of the infection and according to expert's opinion, the efficiency of these regimens has fallen gradually in recent years to unacceptably low levels; however, in the author's opinion this is a multifactorial phenomenon which can not be generalized. As alternative drugs, the efficiency of levofloxacin, furazolidone and rifabutin has been proven by meta-analyses. Sequential and bismuth-free quadruple therapies, although highly efficient, are not yet used on a large scale. The recurrence of the infection is 2.27%/year in developed and of 13.0%/year in developing countries. Spontaneous eradication occurred in 8-20% of the children and 5-11% of adults. The prevalence of clarithromycin resistance is increasing worldwide. In Hungary, it has reached 10.9% in county cities, according to a national survey. In a district of Budapest called Ferencváros, the prevalence between 2005 and 2009 was 16-22%, with no increasing trend. The development of enzymatic inhibitors (urease, carbonic anhydrase and gamma-glutamyl transpeptidase), modified antibiotics and efflux pump inhibitors seem promising ways because these compounds do not lead to resistance; however, none have yet been used in humans.

  3. Characterization of plasma membrane domains of mouse EL4 lymphoma cells obtained by affinity chromatography on concanavalin A-Sepharose.

    PubMed

    Szamel, M; Goppelt, M; Resch, K

    1985-12-19

    Purified plasma membranes of mouse EL4 lymphoma cells were fractionated by means of affinity chromatography on concanavalin A-Sepharose into two subfractions; one (MF1) eluted freely from the affinity column, the second (MF2) adhered specifically to Con A-Sepharose. Both membrane subfractions proved to be of plasma membrane origin, as evidenced by the following criteria. (i) The ratio of cholesterol to phospholipid was nearly identical in plasma membrane and both subfractions. (ii) When isolated plasma membranes were labelled with tritiated NaBH4, both subfractions exhibited identical specific radioactivities. (iii) After enzymatic radioiodination of the cells, the total content of labelled proteins was very similar in isolated plasma membranes and in both subfractions. (iv) Some plasma membrane marker enzymes exhibited nearly identical specific activities in plasma membranes, MF1 or MF2 including gamma-glutamyl transpeptidase, 5'-nucleotidase and Mg2+-ATPase. Both subfractions exhibited characteristic differences. Thus the specific activities of (Na+ + K+)-ATPase, Ca2+-ATPase and lysophosphatidylcholine acyltransferase were several-fold enriched in MF2 compared to MF1. SDS-polyacrylamide gel electrophoresis revealed a different polypeptide composition of the two subfractions. Polypeptides of apparent molecular mass of 116, 95, 42, 39, 30 and 28 kDa were highly enriched in MF2, whereas MF1 contained another set of proteins, of apparent molecular mass of 70, 55 and 24 kDa. The phospholipid fatty acid composition of the subfractions proved to be different, as well, MF2 contained more saturated fatty acids than MF1. The data suggest the existence of plasma membrane domains in the plasma membranes of the mouse EL4 lymphoma cells, containing a set of polypeptides, among others membrane bound enzymes, embedded in a different phospholipid milieu.

  4. Rib fractures in chronic alcoholic men: Relationship with feeding habits, social problems, malnutrition, bone alterations, and liver dysfunction.

    PubMed

    González-Reimers, Emilio; García-Valdecasas-Campelo, Elena; Santolaria-Fernández, Francisco; Milena-Abril, Antonio; Rodríguez-Rodríguez, Eva; Martínez-Riera, Antonio; Pérez-Ramírez, Alina; Alemán-Valls, María Remedios

    2005-10-01

    Rib fractures are common in alcoholics. This high prevalence might be due to ethanol-associated malnutrition, bone disease, liver dysfunction, or the peculiar lifestyle of the alcoholic with frequent trauma and altercations. In this study we try to discern the role of these factors on rib fracture (assessed on a plain thoracic X-ray film) in 81 consecutive alcoholic patients, 25 of them cirrhotics. Serum albumin, prothrombin aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transpeptidase, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin growth factor 1, 1,25-dihydroxyvitamin D, parathyroid hormone, estradiol, free testosterone, and corticosterone were measured, and the patients also underwent assessment of bone mineral density by a HOLOGIC QDR-2000 bone densitometer (Waltham, MA, USA). Body mass index, triceps skinfold, and brachial perimeter were also determined, and the patients and their families were asked about tobacco consumption, social and familial links, consumption of ethanol by other members of the family, kind of job, and feeding habits. Forty-two male nondrinker sanitary workers of similar age served as controls. Forty of the 81 patients showed rib fractures. There was a statistically significant association between rib fractures and disruption of social and familial links, irregular feeding habits (in bars or pubs, not at home), ethanol consumption by close relatives, and intensity of tobacco consumption, but not between rib fractures and liver function tests, nutritional parameters, or bone mineral density, besides a nearly significant trend (p = .053) with the presence of osteopenia at the femoral neck. Patients with major withdrawal symptoms at admission also presented more frequent rib fractures. We conclude that rib fractures in alcoholics are related to the peculiar lifestyle of these patients rather than to bone alterations, liver dysfunction, or nutritional status.

  5. Prolonged intrahepatic cholestasis after exposure to loxoprofen.

    PubMed

    Ichikawa, Takeshi; Sato, Hiroko; Kaira, Kyoichi; Oh-I, Shinsuke; Kakizaki, Satoru; Sato, Ken; Takagi, Hitoshi; Mori, Masatomo

    2008-12-01

    The objective of this report was to describe a case of prolonged intrahepatic cholestasis likely associated with the use of loxoprofen, a phenylpropionate NSAID. A 36-year-old female patient was transferred to Gunma University Hospital, Maebashi, Japan, with progressive pruritus and jaundice that developed after 5-day treatment with 120 mg/d of loxoprofen (maximum recommended dose, 180 mg/d) for menstrual pain. Liver function tests found the following concentrations: total bilirubin, 27.5 mg/dL (normal [nl] range, 0.3-1.2 mg/dL); aspartate aminotransferase, 151 IU/L (nl, 13-33 IU/L); alkaine aminotransferase, 470 IU/L (nl, 8-42 IU/L); alkaline phosphatase, 1082 IU/L (n1, 115-359 IUAL); and gamma-glutamyl transpeptidase, 795 IU/L (nl, 10-47 IU/L) indicative of intrahepatic cholestasis. No use of alcohol or other drugs or herbal products was reported. The patient had a history of elevated hepatic enzymes of unknown origin following the use of mefenamic acid. The patient was prescribed ursodeoxycholic acid 3 weeks after the onset of symptoms of intrahepatic cholestasis. Thereafter, due to progressive cholestasis, an IV pulse of methylprednisolone (1000 mg/d) and the herbal product Inchin-ko-to (TJ-135) were administered. Plasma bilirubin adsorption (PA) and plasma exchange (PE) were performed. Following treatment with PA and PE for 3 weeks with administration of methylprednisolone and Inchin-ko-to, signs and symptoms of intrahepatic cholestasis began to resolve (3.5 months after the onset); they were completely resolved 8 months after the initial episode. A Naranjo scale score of 6 suggested that loxoprofen was likely the cause of the prolonged cholestasis in this patient. Based on the Naranjo score, this case of prolonged intrahepatic cholestasis in a young woman was likely associated with loxoprofen use.

  6. Construction of multiple linear regression models using blood biomarkers for selecting against abdominal fat traits in broilers.

    PubMed

    Dong, J Q; Zhang, X Y; Wang, S Z; Jiang, X F; Zhang, K; Ma, G W; Wu, M Q; Li, H; Zhang, H

    2018-01-01

    Plasma very low-density lipoprotein (VLDL) can be used to select for low body fat or abdominal fat (AF) in broilers, but its correlation with AF is limited. We investigated whether any other biochemical indicator can be used in combination with VLDL for a better selective effect. Nineteen plasma biochemical indicators were measured in male chickens from the Northeast Agricultural University broiler lines divergently selected for AF content (NEAUHLF) in the fed state at 46 and 48 d of age. The average concentration of every parameter for the 2 d was used for statistical analysis. Levels of these 19 plasma biochemical parameters were compared between the lean and fat lines. The phenotypic correlations between these plasma biochemical indicators and AF traits were analyzed. Then, multiple linear regression models were constructed to select the best model used for selecting against AF content. and the heritabilities of plasma indicators contained in the best models were estimated. The results showed that 11 plasma biochemical indicators (triglycerides, total bile acid, total protein, globulin, albumin/globulin, aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, uric acid, creatinine, and VLDL) differed significantly between the lean and fat lines (P < 0.01), and correlated significantly with AF traits (P < 0.05). The best multiple linear regression models based on albumin/globulin, VLDL, triglycerides, globulin, total bile acid, and uric acid, had higher R2 (0.73) than the model based only on VLDL (0.21). The plasma parameters included in the best models had moderate heritability estimates (0.21 ≤ h2 ≤ 0.43). These results indicate that these multiple linear regression models can be used to select for lean broiler chickens. © 2017 Poultry Science Association Inc.

  7. Clinical usefulness of metabolic risk factors to identify young asymptomatic women adults with subclinical atherosclerosis: A cross-sectional study.

    PubMed

    Qin, Guangming; Chen, Zhihao; Su, Weiwei; Geng, Xiaoge; Chen, Xiaojun; Xu, Xiang; Pan, Wensheng

    2017-03-01

    Interventions of cardiovascular disease should be implemented in early ages. But most studies were performed in middle aged or elderly adults because of the low prevalence in young, especially for women. We investigate the association between metabolic risk factors and subclinical atherosclerosis in young asymptomatic women adults, using carotid intima-media thickness (CIMT) as a marker of the atherosclerotic process.We performed a cross-sectional study of 950 Chinese young asymptomatic women adults (37.28 ± 5.16 years) who underwent a routine health screening examination. Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), fasting blood glucose (FBG), homocysteine (HCY), gamma glutamyltransferase (GGT), uric acid, and CIMT were measured.Out of 950 subjects, 16 (1.7%) were detected with increased CIMT. Significant differences existed in the indicators including age, body mass index (BMI), TC, TG, LDL-C, LDL-C/HDL-C, non-HDL-C, and TC/HDL-C. Although TG, LDL-C, non-HDL-C, TC/HDL-C, and TG/HDL-C were the significant indicators when adjusted for age only, age, LDL-C/HDL-C, FBG, and GGT were the only independent relative indicators of increased CMIT that entered the multivariate model. The area under receiver operating characteristic curve for a linear combination of age, LDL-C/HDL-C, FBG, and GGT was 0.809 (95% confidence interval = 0.712-0.906), superior to any of the variables taken alone (age, AUC = 0.707; FBG, AUC = 0.710; LDL-C/HDL-C, AUC = 0.695; GGT, AUC = 0.648).The combined assessment of age, LDL-C/HDL-C, FBG, and GGT contributes to an early detection for subclinical atherosclerosis, providing guidance to clinicians for women's early interventions of latent cardiovascular disease. Neither of the above four individual indicators is qualified alone.

  8. gamma-Hexachlorocyclohexane (gamma-HCH)

    Integrated Risk Information System (IRIS)

    gamma - Hexachlorocyclohexane ( gamma - HCH ) ; CASRN 58 - 89 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Asse

  9. Unidentified Gamma-Ray Sources: Hunting Gamma-Ray Blazars

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

    Massaro, F.; D'Abrusco, R.; Tosti, G.

    2012-04-02

    One of the main scientific objectives of the ongoing Fermi mission is unveiling the nature of the unidentified {gamma}-ray sources (UGSs). Despite the large improvements of Fermi in the localization of {gamma}-ray sources with respect to the past {gamma}-ray missions, about one third of the Fermi-detected objects are still not associated to low energy counterparts. Recently, using the Wide-field Infrared Survey Explorer (WISE) survey, we discovered that blazars, the rarest class of Active Galactic Nuclei and the largest population of {gamma}-ray sources, can be recognized and separated from other extragalactic sources on the basis of their infrared (IR) colors. Basedmore » on this result, we designed an association method for the {gamma}-ray sources to recognize if there is a blazar candidate within the positional uncertainty region of a generic {gamma}-ray source. With this new IR diagnostic tool, we searched for {gamma}-ray blazar candidates associated to the UGS sample of the second Fermi {gamma}-ray catalog (2FGL). We found that our method associates at least one {gamma}-ray blazar candidate as a counterpart each of 156 out of 313 UGSs analyzed. These new low-energy candidates have the same IR properties as the blazars associated to {gamma}-ray sources in the 2FGL catalog.« less

  10. UNIDENTIFIED {gamma}-RAY SOURCES: HUNTING {gamma}-RAY BLAZARS

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

    Massaro, F.; Ajello, M.; D'Abrusco, R.

    2012-06-10

    One of the main scientific objectives of the ongoing Fermi mission is unveiling the nature of unidentified {gamma}-ray sources (UGSs). Despite the major improvements of Fermi in the localization of {gamma}-ray sources with respect to the past {gamma}-ray missions, about one-third of the Fermi-detected objects are still not associated with low-energy counterparts. Recently, using the Wide-field Infrared Survey Explorer survey, we discovered that blazars, the rarest class of active galactic nuclei and the largest population of {gamma}-ray sources, can be recognized and separated from other extragalactic sources on the basis of their infrared (IR) colors. Based on this result, wemore » designed an association method for the {gamma}-ray sources to recognize if there is a blazar candidate within the positional uncertainty region of a generic {gamma}-ray source. With this new IR diagnostic tool, we searched for {gamma}-ray blazar candidates associated with the UGS sample of the second Fermi {gamma}-ray LAT catalog (2FGL). We found that our method associates at least one {gamma}-ray blazar candidate as a counterpart to each of 156 out of 313 UGSs analyzed. These new low-energy candidates have the same IR properties as the blazars associated with {gamma}-ray sources in the 2FGL catalog.« less

  11. Growth kinetics of gamma-prime precipitates in a directionally solidified eutectic, gamma/gamma-prime-delta

    NASA Technical Reports Server (NTRS)

    Tewari, S. N.

    1976-01-01

    A directionally solidified eutectic alloy (DSEA), of those viewed as potential candidates for the next generation of aircraft gas turbine blade materials, is studied for the gamma-prime growth kinetics, in the system Ni-Nb-Cr-Al, specifically: Ni-20 w/o Nb-6 w/o Cr-2.5 w/o Al gamma/gamma-prime-delta DSEA. Heat treatment, polishing and etching, and preparation for electron micrography are described, and the size distribution of gamma-prime phase following various anneals is plotted, along with gamma-prime growth kinetics in this specific DSEA, and the cube of gamma-prime particle size vs anneal time. Activation energies and coarsening kinetics are studied.

  12. The neutron-gamma Feynman variance to mean approach: Gamma detection and total neutron-gamma detection (theory and practice)

    NASA Astrophysics Data System (ADS)

    Chernikova, Dina; Axell, Kåre; Avdic, Senada; Pázsit, Imre; Nordlund, Anders; Allard, Stefan

    2015-05-01

    Two versions of the neutron-gamma variance to mean (Feynman-alpha method or Feynman-Y function) formula for either gamma detection only or total neutron-gamma detection, respectively, are derived and compared in this paper. The new formulas have particular importance for detectors of either gamma photons or detectors sensitive to both neutron and gamma radiation. If applied to a plastic or liquid scintillation detector, the total neutron-gamma detection Feynman-Y expression corresponds to a situation where no discrimination is made between neutrons and gamma particles. The gamma variance to mean formulas are useful when a detector of only gamma radiation is used or when working with a combined neutron-gamma detector at high count rates. The theoretical derivation is based on the Chapman-Kolmogorov equation with the inclusion of general reactions and corresponding intensities for neutrons and gammas, but with the inclusion of prompt reactions only. A one energy group approximation is considered. The comparison of the two different theories is made by using reaction intensities obtained in MCNPX simulations with a simplified geometry for two scintillation detectors and a 252Cf-source. In addition, the variance to mean ratios, neutron, gamma and total neutron-gamma are evaluated experimentally for a weak 252Cf neutron-gamma source, a 137Cs random gamma source and a 22Na correlated gamma source. Due to the focus being on the possibility of using neutron-gamma variance to mean theories for both reactor and safeguards applications, we limited the present study to the general analytical expressions for Feynman-alpha formulas.

  13. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid.

    PubMed

    Hirschfield, Gideon M; Mason, Andrew; Luketic, Velimir; Lindor, Keith; Gordon, Stuart C; Mayo, Marlyn; Kowdley, Kris V; Vincent, Catherine; Bodhenheimer, Henry C; Parés, Albert; Trauner, Michael; Marschall, Hanns-Ulrich; Adorini, Luciano; Sciacca, Cathi; Beecher-Jones, Tessa; Castelloe, Erin; Böhm, Olaf; Shapiro, David

    2015-04-01

    We evaluated the efficacy and safety of obeticholic acid (OCA, α-ethylchenodeoxycholic acid) in a randomized controlled trial of patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid therapy. We performed a double-blind study of 165 patients with primary biliary cirrhosis (95% women) and levels of alkaline phosphatase (ALP) 1.5- to 10-fold the upper limit of normal. Patients were randomly assigned to groups given 10 mg, 25 mg, or 50 mg doses of OCA or placebo, once daily for 3 months. Patients maintained their existing dose of ursodeoxycholic acid throughout the study. The primary outcome was change in level of ALP from baseline (day 0) until the end of the study (day 85 or early termination). We also performed an open-label extension of the trial in which 78 patients were enrolled and 61 completed the first year. OCA was superior to placebo in achieving the primary end point. Subjects given OCA had statistically significant relative reductions in mean ALP from baseline to the end of the study (P < .0001 all OCA groups vs placebo). Levels of ALP decreased 21%-25% on average from baseline in the OCA groups and 3% in the placebo group. Sixty-nine percent (68 of 99) of patients given OCA had at least a 20% reduction in ALP compared with 8% (3 of 37) of patients given placebo (P < .0003). Among secondary end points, levels of γ-glutamyl transpeptidase decreased 48%-63%, on average, among subjects given OCA, vs a 7% decrease in the group given placebo; levels of alanine aminotransferase decreased 21%-35% on average among subjects given OCA vs none of the patients given placebo. Pruritus was the principal adverse event; incidence values in the OCA 10 mg, 25 mg, and 50 mg groups were 47% (not significantly different), 87% (P < .0003), and 80% (P < .006), respectively, vs 50% in the placebo group. In the extension study, levels of ALP continued to decrease to a mean level of 202 ± 11 U/L after 12 months vs 285 ± 15 U/L at

  14. Targeting the cell wall of Mycobacterium tuberculosis: a molecular modeling investigation of the interaction of imipenem and meropenem with L,D-transpeptidase 2.

    PubMed

    Silva, José Rogério A; Bishai, William R; Govender, Thavendran; Lamichhane, Gyanu; Maguire, Glenn E M; Kruger, Hendrik G; Lameira, Jeronimo; Alves, Cláudio N

    2016-01-01

    The single crystal X-ray structure of the extracellular portion of the L,D-transpeptidase (ex-LdtMt2 - residues 120-408) enzyme was recently reported. It was observed that imipenem and meropenem inhibit activity of this enzyme, responsible for generating L,D-transpeptide linkages in the peptidoglycan layer of Mycobacterium tuberculosis. Imipenem is more active and isothermal titration calorimetry experiments revealed that meropenem is subjected to an entropy penalty upon binding to the enzyme. Herein, we report a molecular modeling approach to obtain a molecular view of the inhibitor/enzyme interactions. The average binding free energies for nine commercially available inhibitors were calculated using MM/GBSA and Solvation Interaction Energy (SIE) approaches and the calculated energies corresponded well with the available experimentally observed results. The method reproduces the same order of binding energies as experimentally observed for imipenem and meropenem. We have also demonstrated that SIE is a reasonably accurate and cost-effective free energy method, which can be used to predict carbapenem affinities for this enzyme. A theoretical explanation was offered for the experimental entropy penalty observed for meropenem, creating optimism that this computational model can serve as a potential computational model for other researchers in the field.

  15. Very high-energy gamma rays from gamma-ray bursts.

    PubMed

    Chadwick, Paula M

    2007-05-15

    Very high-energy (VHE) gamma-ray astronomy has undergone a transformation in the last few years, with telescopes of unprecedented sensitivity having greatly expanded the source catalogue. Such progress makes the detection of a gamma-ray burst at the highest energies much more likely than previously. This paper describes the facilities currently operating and their chances for detecting gamma-ray bursts, and reviews predictions for VHE gamma-ray emission from gamma-ray bursts. Results to date are summarized.

  16. Chromatographic methods for determination of S-substituted cysteine derivatives--a comparative study.

    PubMed

    Kubec, Roman; Dadáková, Eva

    2009-10-09

    A novel HPLC method for determination of a wide variety of S-substituted cysteine derivatives in Allium species has been developed and validated. This method allows simultaneous separation and quantification of S-alk(en)ylcysteine S-oxides, gamma-glutamyl-S-alk(en)ylcysteines and gamma-glutamyl-S-alk(en)ylcysteine S-oxides in a single run. The procedure is based on extraction of these amino acids and dipeptides by methanol, their derivatization by dansyl chloride and subsequent separation by reversed phase HPLC. The main advantages of the new method are simplicity, excellent stability of derivatives, high sensitivity, specificity and the ability to simultaneously analyze the whole range of S-substituted cysteine derivatives. This method was critically compared with other chromatographic procedures used for quantification of S-substituted cysteine derivatives, namely with two other HPLC methods (derivatization by o-phthaldialdehyde/tert-butylthiol and fluorenylmethyl chloroformate), and with determination by gas chromatography or capillary electrophoresis. Major advantages and drawbacks of these analytical procedures are discussed. Employing these various chromatographic methods, the content and relative proportions of individual S-substituted cysteine derivatives were determined in four most frequently consumed alliaceous vegetables (garlic, onion, shallot, and leek).

  17. A Survey of Glutamine Synthetase Activities in Tissues from Three Classes of Fish.

    DTIC Science & Technology

    1980-09-01

    reveree side it necessay end identify by block enamaber) Glutamine synthetase, gamma-glutamyl transferase, osmoregulation , glutamate, glutamine...aspects of osmoregulation as well. The only known route of glutanmine synthesis n all species is activity of glutamine synthetase (EC 6.3.1.2) which...for osmoregulation . There is a relatively small difference n species which retain urea for osmoregulation . This may help to explain the relationship of

  18. Nonprotein amino acids from seeds of Cycas circinalis and Phaseolus vulgaris.

    PubMed

    Li, C J; Brownson, D M; Mabry, T J; Perera, C; Bell, E A

    1996-05-01

    Our chemical studies on Cycas circinalis seeds from Guam has provided two new nonprotein amino acids, N-(3'-one-5'-methyl)-hexylalanine and leucine betaine. N-methylisoleucine, previously reported as a component of naturally occurring peptides, has been isolated as a free amino acid from the seeds of Phaseolus vulgaris (pinto bean), together with S-methylcysteine, pipecolic acid and a dipeptide, gamma-glutamyl-leucine.

  19. Capsule Depolymerase Overexpression Reduces Bacillus anthracis Virulence

    DTIC Science & Technology

    2010-01-01

    protein that autocatalytically forms a heterodimer consisting of 35 kDa and 15 kDa subunits. CapD shares 32 % identity with the Bacillus subtilis GGT and 35...Immun 49, 291–297. Kimura, K., Tran, L. S., Uchida, I. & Itoh, Y. (2004). Characterization of Bacillus subtilis gamma-glutamyltransferase and its...Capsule depolymerase overexpression reduces Bacillus anthracis virulence Angelo Scorpio,3 Donald J. Chabot, William A. Day,4 Timothy A. Hoover and

  20. Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls.

    PubMed

    Shen, Yi; Zhang, Jian; Cai, Hui; Shao, Jian-Guo; Zhang, You-Yi; Liu, Yan-Mei; Qin, Gang; Qin, Yan

    2015-03-19

    The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.

  1. Blood mercury concentrations are associated with decline in liver function in an elderly population: a panel study.

    PubMed

    Lee, Mee-Ri; Lim, Youn-Hee; Lee, Bo-Eun; Hong, Yun-Chul

    2017-03-04

    Mercury is a toxic heavy metal and is known to affect many diseases. However, few studies have examined the effects of mercury exposure on liver function in the general population. We examined the association between blood mercury concentrations and liver enzyme levels in the elderly. We included 560 elderly participants (60 years or older) who were recruited from 2008 to 2010 and followed up to 2014. Subjects visited a community welfare center and underwent a medical examination and measurement of mercury levels up to five times. Analyses using generalized estimating equations model were performed after adjusting for age, sex, education, overweight, alcohol consumption, smoking, regular exercise, high-density lipoproteins cholesterol, and total calorie intake. Additionally, we estimated interaction effects of alcohol consumption with mercury and mediation effect of oxidative stress in the relationship between mercury levels and liver function. The geometric mean (95% confidence interval (CI)) of blood mercury concentrations was 2.81 μg/L (2.73, 2.89). Significant relationships were observed between blood mercury concentrations and the level of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT), after adjusting for potential confounders (P < 0.05). The odds ratios of having abnormal ALT levels were statistically significant in the highest mercury quartile compared to those with the lowest quartile. Particularly, regular alcohol drinkers showed greater effect estimates of mercury on the liver function than non-drinkers groups. There was no mediation effect of oxidative stress in the relationship between blood mercury concentrations and liver function. Our results suggest that blood mercury levels are associated with elevated liver enzymes and interact with alcohol consumption for the association in the elderly.

  2. Predictors of fibrosis in Asian patients with non-alcoholic steatohepatitis.

    PubMed

    Tsang, Steven Woon Choy; Ng, Wing Fung; Wu, Brian Ping Ying; Chow, David Alan; Li, Eric Ting Ho; Wong, Tak Cheung

    2006-01-01

    Non-alcoholic steatohepatitis (NASH) is increasingly recognized as an important cause of chronic liver disease. However, data on Asians with NASH is lacking in the literature. The aim of the present study was to describe the clinical, biochemical and histological characteristics of NASH in Asians and to determine the predictors for septal fibrosis. Sixty consecutive patients aged over 18 years with elevated serum alanine transferase, sonographic evidence of steatosis, and consent for liver biopsy were included. Patients with chronic hepatitis B or C, alcoholic, autoimmune, genetic, or drug-induced liver disease were excluded. Clinical, biochemical and histological variables were tested for association with septal liver fibrosis (F2/3). Median age of the cohort was 45.5 years (range 21-75 years) and 63% were male. Ninety percent of patients were obese (body mass index [BMI]>or= 25), 70% had hypertriglyceridemia, 68% had hypercholesterolemia, 58% had metabolic syndrome, 53% had hypertension, 47% had diabetes mellitus (DM), and 18% had obstructive sleep apnea. Sixty-eight percent had gamma-glutamyl transferase (GGT) >or= 2 x upper limit of normal (ULN), 55% had alanine aminotransferase (ALT) >or= 2 x ULN, and 23% had aspartate aminotransferase (AST) >or= 2 x ULN. Of the 40 non-diabetic patients undergoing oral glucose tolerance testing, 45% had normal tests, 30% had impaired glucose tolerance, 23% DM, and 2% impaired fasting glucose. Eighteen patients (30%) had septal fibrosis (F2/3), but none had cirrhosis. Necroinflammatory grade >or= 2 (odds ratio [OR] 13), AST >or= 2 x ULN (OR 5.3) and DM (OR 5) were significantly and independently correlated with septal fibrosis. Septal fibrosis is common in Asians with NASH. Necroinflammatory grade >or= 2, AST >or= 2 x ULN and DM are independent predictors for septal fibrosis.

  3. Coagulation profile, haematological and biochemical changes in kids naturally infected with peste des petits ruminants.

    PubMed

    Sahinduran, Sima; Albay, Metin Koray; Sezer, Kenan; Ozmen, Ozlem; Mamak, Nuri; Haligur, Mehmet; Karakurum, Cagri; Yildiz, Ramazan

    2012-03-01

    The aim of this study was to examine the coagulation profile in peste des petits ruminant (PPR) in kids. Five kids from a group of 150 animals (72 goats and 78 kids) were brought to the Veterinary Medical Teaching Hospital from a farm in Burdur province (Turkey) with nasal and ocular discharges and diarrhea. Fifteen goats and 41 kids had died due to diarrhea and three kids were presented to the Department of Pathology for diagnosis. Blood samples were taken from 12 ill animals (infected group) for haematological and biochemical analysis. In addition, five healthy kids were examined from another healthy flock (control group). Leukocyte and lymphocyte numbers of infected group showed significant declinations in comparison to control group (≤0.001). Haemorrhages in all organs of digestive system and small haemorrhagic areas in liver were caused to decrease in erythrocyte and haematocrit values (p ≤ 0.001) in infected group. Concentrations of blood urea nitrogen (BUN) (p ≤ 0.01) and creatinine (p ≤ 0.001) in infected group were significantly higher than control group. Compared to control group, significant increases were determined in serum concentrations of alkaline phosphatase (ALP) (p ≤ 0.01), aspartate aminotransferase (AST) (p ≤ 0.001) and alanine aminotransferase (ALT) (p ≤ 0.001) in the infected group. No significant differences were observed between the infected and control groups for serum gamma glutamyl-transferase (GGT) concentration value. In our study, thrombocytopenia (p ≤ 0.001) together with prolonged activated partial thromboplastin time (APTT; p ≤ 0.01) and prothrombin time (PT; p ≤ 0.001) may show that disseminated intravascular coagulopathy which can occur in kids with PPR.

  4. Contribution of Inflammation, Oxidative Stress, and Antioxidants to the Relationship between Sleep Duration and Cardiometabolic Health.

    PubMed

    Kanagasabai, Thirumagal; Ardern, Chris I

    2015-12-01

    To explore the interrelationship and mediating effect of factors that are beneficial (i.e., antioxidants) and harmful (i.e., inflammation and oxidative stress) to the relationship between sleep and cardiometabolic health. Cross-sectional data from the 2005-2006 National Health and Nutrition Examination Survey. Nationally representative population sample from the US. Age ≥ 20 y with sleep data; final analytical sample of n = 2,079. N/A. Metabolic syndrome was classified according to the Joint Interim Statement, and sleep duration was categorized as very short, short, adequate, and long sleepers (≤ 4, 5-6, 7-8, and ≥ 9 h per night, respectively). The indirect mediation effect was quantified as large (≥ 0.25), moderate (≥ 0.09), modest (≥ 0.01), and weak (< 0.01). In general, inflammation was above the current clinical reference range across all sleep duration categories, whereas oxidative stress was elevated among short and very short sleepers. Select sleep duration- cardiometabolic health relationships were mediated by C-reactive protein (CRP), γ-glutamyl transferase (GGT), carotenoids, uric acid, and vitamins C and D, and were moderated by sex. Specifically, moderate-to-large indirect mediation by GGT, carotenoids, uric acid, and vitamin D were found for sleep duration-waist circumference and -systolic blood pressure relationships, whereas vitamin C was a moderate mediator of the sleep duration-diastolic blood pressure relationship. Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the casual pathway of the sleep duration-cardiometabolic health relationship. Further longitudinal studies are needed to confirm our results. © 2015 Associated Professional Sleep Societies, LLC.

  5. Translational informatics approach for identifying the functional molecular communicators linking coronary artery disease, infection and inflammation

    PubMed Central

    SHARMA, ANKIT; GHATGE, MADANKUMAR; MUNDKUR, LAKSHMI; VANGALA, RAJANI KANTH

    2016-01-01

    Translational informatics approaches are required for the integration of diverse and accumulating data to enable the administration of effective translational medicine specifically in complex diseases such as coronary artery disease (CAD). In the current study, a novel approach for elucidating the association between infection, inflammation and CAD was used. Genes for CAD were collected from the CAD-gene database and those for infection and inflammation were collected from the UniProt database. The cytomegalovirus (CMV)-induced genes were identified from the literature and the CAD-associated clinical phenotypes were obtained from the Unified Medical Language System. A total of 55 gene ontologies (GO) termed functional communicator ontologies were identifed in the gene sets linking clinical phenotypes in the diseasome network. The network topology analysis suggested that important functions including viral entry, cell adhesion, apoptosis, inflammatory and immune responses networked with clinical phenotypes. Microarray data was extracted from the Gene Expression Omnibus (dataset: GSE48060) for highly networked disease myocardial infarction. Further analysis of differentially expressed genes and their GO terms suggested that CMV infection may trigger a xenobiotic response, oxidative stress, inflammation and immune modulation. Notably, the current study identified γ-glutamyl transferase (GGT)-5 as a potential biomarker with an odds ratio of 1.947, which increased to 2.561 following the addition of CMV and CMV-neutralizing antibody (CMV-NA) titers. The C-statistics increased from 0.530 for conventional risk factors (CRFs) to 0.711 for GGT in combination with the above mentioned infections and CRFs. Therefore, the translational informatics approach used in the current study identified a potential molecular mechanism for CMV infection in CAD, and a potential biomarker for risk prediction. PMID:27035874

  6. Cyclopiazonic acid augments the hepatic and renal oxidative stress in broiler chicks.

    PubMed

    Malekinejad, H; Akbari, P; Allymehr, M; Hobbenaghi, R; Rezaie, A

    2011-08-01

    Generation of reactive oxygen species (ROS) leads to serious tissue injuries. The effect of cyclopiazonic acid (CPA) on oxidative stress markers in the liver and kidneys of broiler chicks was studied. Ten-day-old male broiler chicks (Ross 308) were assigned into the control and test groups, which received normal saline and 10, 25, and 50 μg/kg CPA, respectively, for 28 days. Body weight gain, serum level of alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), uric acid, creatinine, and blood urea nitrogen (BUN) were measured after 2 and 4 weeks exposure. Moreover, the total thiol molecules (TTM) and malondialdehyde (MDA) content of the liver and kidneys were assessed. No significant differences (p > 0.05) were found in body weight gain between the control and test groups. Whereas, the hepatic weight increased significantly (p < 0.05) in animals that received 25 and 50 μg/kg CPA. Both ALP and GGT level in serum were elevated in comparison to the control group. CPA also resulted in uric acid, creatinine, and BUN enhancement in broilers. The MDA content of the liver and kidneys showed remarkable increase. By contrast, the TTM levels in the liver and kidneys were significantly (p < 0.05) attenuated. Histopathological findings confirmed the biochemical changes in either organ characterized by inflammatory cells infiltration along with severe congestion and cell swelling, suggesting an inflammatory response. These data suggest that exposure to CPA resulted in hepatic and renal disorders, which were reflected as biochemical markers alteration and pathological injuries in either organ. The biochemical alteration and pathological abnormalities may be attributed to CPA-induced oxidative stress.

  7. Gamma-sky.net: Portal to the gamma-ray sky

    NASA Astrophysics Data System (ADS)

    Voruganti, Arjun; Deil, Christoph; Donath, Axel; King, Johannes

    2017-01-01

    http://gamma-sky.net is a novel interactive website designed for exploring the gamma-ray sky. The Map View portion of the site is powered by the Aladin Lite sky atlas, providing a scalable survey image tesselated onto a three-dimensional sphere. The map allows for interactive pan and zoom navigation as well as search queries by sky position or object name. The default image overlay shows the gamma-ray sky observed by the Fermi-LAT gamma-ray space telescope. Other survey images (e.g. Planck microwave images in low/high frequency bands, ROSAT X-ray image) are available for comparison with the gamma-ray data. Sources from major gamma-ray source catalogs of interest (Fermi-LAT 2FHL, 3FGL and a TeV source catalog) are overlaid over the sky map as markers. Clicking on a given source shows basic information in a popup, and detailed pages for every source are available via the Catalog View component of the website, including information such as source classification, spectrum and light-curve plots, and literature references. We intend for gamma-sky.net to be applicable for both professional astronomers as well as the general public. The website started in early June 2016 and is being developed as an open-source, open data project on GitHub (https://github.com/gammapy/gamma-sky). We plan to extend it to display more gamma-ray and multi-wavelength data. Feedback and contributions are very welcome!

  8. Staphylococcus aureus HemX Modulates Glutamyl-tRNA Reductase Abundance To Regulate Heme Biosynthesis

    PubMed Central

    Choby, Jacob E.; Grunenwald, Caroline M.; Celis, Arianna I.; Gerdes, Svetlana Y.; DuBois, Jennifer L.

    2018-01-01

    ABSTRACT Staphylococcus aureus is responsible for a significant amount of devastating disease. Its ability to colonize the host and cause infection is supported by a variety of proteins that are dependent on the cofactor heme. Heme is a porphyrin used broadly across kingdoms and is synthesized de novo from common cellular precursors and iron. While heme is critical to bacterial physiology, it is also toxic in high concentrations, requiring that organisms encode regulatory processes to control heme homeostasis. In this work, we describe a posttranscriptional regulatory strategy in S. aureus heme biosynthesis. The first committed enzyme in the S. aureus heme biosynthetic pathway, glutamyl-tRNA reductase (GtrR), is regulated by heme abundance and the integral membrane protein HemX. GtrR abundance increases dramatically in response to heme deficiency, suggesting a mechanism by which S. aureus responds to the need to increase heme synthesis. Additionally, HemX is required to maintain low levels of GtrR in heme-proficient cells, and inactivation of hemX leads to increased heme synthesis. Excess heme synthesis in a ΔhemX mutant activates the staphylococcal heme stress response, suggesting that regulation of heme synthesis is critical to reduce self-imposed heme toxicity. Analysis of diverse organisms indicates that HemX is widely conserved among heme-synthesizing bacteria, suggesting that HemX is a common factor involved in the regulation of GtrR abundance. Together, this work demonstrates that S. aureus regulates heme synthesis by modulating GtrR abundance in response to heme deficiency and through the activity of the broadly conserved HemX. PMID:29437922

  9. Resonance production in. gamma gamma. collisions

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

    Renard, F.M.

    1983-04-01

    The processes ..gamma gamma.. ..-->.. hadrons can be depicted as follows. One photon creates a q anti q pair which starts to evolve; the other photon can either (A) make its own q anti q pair and the (q anti q q anti q) system continue to evolve or (B) interact with the quarks of the first pair and lead to a modified (q anti q) system in interaction with C = +1 quantum numbers. A review of the recent theoretical activity concerning resonance production and related problems is given under the following headings: hadronic C = +1 spectroscopy (qmore » anti q, qq anti q anti q, q anti q g, gg, ggg bound states and mixing effects); exclusive ..gamma gamma.. processes (generalities, unitarized Born method, VDM and QCD); total cross section (soft and hard contributions); q/sup 2/ dependence of soft processes (soft/hard separation, 1/sup +- +/ resonances); and polarization effects. (WHK)« less

  10. Alcohol abuse and liver enzymes (AALE): results of an intercompany study of mortality.

    PubMed

    Titcomb, C; Braun, R; Roudebush, B; Mast, J; Woodman, H

    2001-01-01

    Evaluation of applicants for life insurance who have elevations of their liver function tests or an increased probability of alcohol abuse has always been difficult for underwriters. This paper reports the results of an intercompany study in which the pooled mortality experience of a group of insureds with evidence of alcohol abuse, an adverse driving record or elevations of the liver transaminases or gamma-glutamyl transferase is summarized.

  11. The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

    PubMed Central

    2013-01-01

    Background Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. Methods A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Results Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels

  12. Method of incident low-energy gamma-ray direction reconstruction in the GAMMA-400 gamma-ray space telescope

    NASA Astrophysics Data System (ADS)

    Kheymits, M. D.; Leonov, A. A.; Zverev, V. G.; Galper, A. M.; Arkhangelskaya, I. V.; Arkhangelskiy, A. I.; Suchkov, S. I.; Topchiev, N. P.; Yurkin, Yu T.; Bakaldin, A. V.; Dalkarov, O. D.

    2016-02-01

    The GAMMA-400 gamma-ray space-based telescope has as its main goals to measure cosmic γ-ray fluxes and the electron-positron cosmic-ray component produced, theoretically, in dark-matter-particles decay or annihilation processes, to search for discrete γ-ray sources and study them in detail, to examine the energy spectra of diffuse γ-rays — both galactic and extragalactic — and to study gamma-ray bursts (GRBs) and γ-rays from the active Sun. Scientific goals of GAMMA-400 telescope require fine angular resolution. The telescope is of a pair-production type. In the converter-tracker, the incident gamma-ray photon converts into electron-positron pair in the tungsten layer and then the tracks are detected by silicon- strip position-sensitive detectors. Multiple scattering processes become a significant obstacle in the incident-gamma direction reconstruction for energies below several gigaelectronvolts. The method of utilising this process to improve the resolution is proposed in the presented work.

  13. Design and Performance of the GAMMA-400 Gamma-Ray Telescope for Dark Matter Searches

    NASA Technical Reports Server (NTRS)

    Galper, A.M.; Adriani, O.; Aptekar, R. L.; Arkhangelskaja, I. V.; Arkhangelskiy, A.I.; Boezio, M.; Bonvicini, V.; Boyarchuk, K. A.; Fradkin, M. I.; Gusakov, Yu. V.; hide

    2012-01-01

    The GAMMA-400 gamma-ray telescope is designed to measure the fluxes of gamma-rays and cosmic-ray electrons + positrons, which can be produced by annihilation or decay of the dark matter particles, as well as to survey the celestial sphere in order to study point and extended sources of gamma-rays, measure energy spectra of Galactic and extragalactic diffuse gamma-ray emission, gamma-ray bursts, and gamma-ray emission from the Sun. GAMMA-400 covers the energy range from 100 MeV to 3000 GeV. Its angular resolution is approx. 0.01 deg (E(sub gamma) > 100 GeV), the energy resolution approx. 1% (E(sub gamma) > 10 GeV), and the proton rejection factor approx 10(exp 6). GAMMA-400 will be installed on the Russian space platform Navigator. The beginning of observations is planned for 2018.

  14. A Novel Glutamyl (Aspartyl)-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application.

    PubMed

    Stressler, Timo; Ewert, Jacob; Merz, Michael; Funk, Joshua; Claaßen, Wolfgang; Lutz-Wahl, Sabine; Schmidt, Herbert; Kuhn, Andreas; Fischer, Lutz

    2016-01-01

    Lactic acid bacteria (LAB) are auxotrophic for a number of amino acids. Thus, LAB have one of the strongest proteolytic systems to acquit their amino acid requirements. One of the intracellular exopeptidases present in LAB is the glutamyl (aspartyl) specific aminopeptidase (PepA; EC 3.4.11.7). Most of the PepA enzymes characterized yet, belonged to Lactococcus lactis sp., but no PepA from a Lactobacillus sp. has been characterized so far. In this study, we cloned a putative pepA gene from Lb. delbrueckii ssp. lactis DSM 20072 and characterized it after purification. For comparison, we also cloned, purified and characterized PepA from Lc. lactis ssp. lactis DSM 20481. Due to the low homology between both enzymes (30%), differences between the biochemical characteristics were very likely. This was confirmed, for example, by the more acidic optimum pH value of 6.0 for Lb-PepA compared to pH 8.0 for Lc-PepA. In addition, although the optimum temperature is quite similar for both enzymes (Lb-PepA: 60°C; Lc-PepA: 65°C), the temperature stability after three days, 20°C below the optimum temperature, was higher for Lb-PepA (60% residual activity) than for Lc-PepA (2% residual activity). EDTA inhibited both enzymes and the strongest activation was found for CoCl2, indicating that both enzymes are metallopeptidases. In contrast to Lc-PepA, disulfide bond-reducing agents such as dithiothreitol did not inhibit Lb-PepA. Finally, Lb-PepA was not product-inhibited by L-Glu, whereas Lc-PepA showed an inhibition.

  15. A Novel Glutamyl (Aspartyl)-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application

    PubMed Central

    Stressler, Timo; Ewert, Jacob; Merz, Michael; Funk, Joshua; Claaßen, Wolfgang; Lutz-Wahl, Sabine; Schmidt, Herbert; Kuhn, Andreas; Fischer, Lutz

    2016-01-01

    Lactic acid bacteria (LAB) are auxotrophic for a number of amino acids. Thus, LAB have one of the strongest proteolytic systems to acquit their amino acid requirements. One of the intracellular exopeptidases present in LAB is the glutamyl (aspartyl) specific aminopeptidase (PepA; EC 3.4.11.7). Most of the PepA enzymes characterized yet, belonged to Lactococcus lactis sp., but no PepA from a Lactobacillus sp. has been characterized so far. In this study, we cloned a putative pepA gene from Lb. delbrueckii ssp. lactis DSM 20072 and characterized it after purification. For comparison, we also cloned, purified and characterized PepA from Lc. lactis ssp. lactis DSM 20481. Due to the low homology between both enzymes (30%), differences between the biochemical characteristics were very likely. This was confirmed, for example, by the more acidic optimum pH value of 6.0 for Lb-PepA compared to pH 8.0 for Lc-PepA. In addition, although the optimum temperature is quite similar for both enzymes (Lb-PepA: 60°C; Lc-PepA: 65°C), the temperature stability after three days, 20°C below the optimum temperature, was higher for Lb-PepA (60% residual activity) than for Lc-PepA (2% residual activity). EDTA inhibited both enzymes and the strongest activation was found for CoCl2, indicating that both enzymes are metallopeptidases. In contrast to Lc-PepA, disulfide bond-reducing agents such as dithiothreitol did not inhibit Lb-PepA. Finally, Lb-PepA was not product-inhibited by L-Glu, whereas Lc-PepA showed an inhibition. PMID:27003449

  16. Cosmic Gamma-Rays

    Science.gov Websites

    [Argonne Logo] [DOE Logo] Cosmic Gamma-Rays Home Publications Talks People Students Argonne > ; HEP > Cosmic Gamma-Rays Projects VERITAS Past Projects TrICE What's New CTA Cosmic Gamma-Rays The

  17. Design and Performance of the GAMMA-400 Gamma-Ray Telescope for Dark Matter Searches

    NASA Technical Reports Server (NTRS)

    Galper, A. M.; Adriani, O.; Aptekar, R. L.; Arkhangelskaja, I. V.; Arkhangelskiy, A. I.; Boezio, M.; Bonvicini, V.; Boyarchuk, K. A.; Fradkin, M. I.; Gusakov, Yu V.; hide

    2012-01-01

    The GAMMA-400 gamma-ray telescope is designed to measure the fluxes of gamma-rays and cosmic-ray electrons (+) positrons, which can be produced by annihilation or decay of the dark matter particles, as well as to survey the celestial sphere in order to study point and extended sources of gamma-rays, measure energy spectra of Galactic and extragalactic diffuse gamma-ray emission, gamma-ray bursts, and gamma-ray emission from the Sun. GAMMA-400 covers the energy range from 100 MeV to 3000 GeV. Its angular resolution is approximately 0.01deg (E(sub gamma) greater than 100 GeV), the energy resolution approximately 1% (E(sub gamma) greater than 10 GeV), and the proton rejection factor approximately 10(exp 6). GAMMA-400 will be installed on the Russian space platform Navigator. The beginning of observations is planned for 2018.

  18. Self-cloning baker's yeasts that accumulate proline enhance freeze tolerance in doughs.

    PubMed

    Kaino, Tomohiro; Tateiwa, Tetsuya; Mizukami-Murata, Satomi; Shima, Jun; Takagi, Hiroshi

    2008-09-01

    We constructed self-cloning diploid baker's yeast strains by disrupting PUT1, encoding proline oxidase, and replacing the wild-type PRO1, encoding gamma-glutamyl kinase, with a pro1(D154N) or pro1(I150T) allele. The resultant strains accumulated intracellular proline and retained higher-level fermentation abilities in the frozen doughs than the wild-type strain. These results suggest that proline-accumulating baker's yeast is suitable for frozen-dough baking.

  19. Cross-sectional associations of total sitting and leisure screen time with cardiometabolic risk in adults. Results from the HUNT Study, Norway.

    PubMed

    Chau, Josephine Y; Grunseit, Anne; Midthjell, Kristian; Holmen, Jostein; Holmen, Turid L; Bauman, Adrian E; van der Ploeg, Hidde P

    2014-01-01

    To examine associations of total sitting time, TV-viewing and leisure-time computer use with cardiometabolic risk biomarkers in adults. Population based cross-sectional study. Waist circumference, BMI, total cholesterol, HDL cholesterol, blood pressure, non-fasting glucose, gamma glutamyltransferase (GGT) and triglycerides were measured in 48,882 adults aged 20 years or older from the Nord-Trøndelag Health Study 2006-2008 (HUNT3). Adjusted multiple regression models were used to test for associations between these biomarkers and self-reported total sitting time, TV-viewing and leisure-time computer use in the whole sample and by cardiometabolic disease status sub-groups. In the whole sample, reporting total sitting time ≥10 h/day was associated with poorer BMI, waist circumference, total cholesterol, HDL cholesterol, diastolic blood pressure, systolic blood pressure, non-fasting glucose, GGT and triglyceride levels compared to those reporting total sitting time <4h/day (all p<0.05). TV-viewing ≥4 h/day was associated with poorer BMI, waist circumference, total cholesterol, HDL cholesterol, systolic blood pressure, GGT and triglycerides compared to TV-viewing <1h/day (all p<0.05). Leisure-time computer use ≥1 h/day was associated with poorer BMI, total cholesterol, diastolic blood pressure, GGT and triglycerides compared with those reporting no leisure-time computing. Sub-group analyses by cardiometabolic disease status showed similar patterns in participants free of cardiometabolic disease, while similar albeit non-significant patterns were observed in those with cardiometabolic disease. Total sitting time, TV-viewing and leisure-time computer use are associated with poorer cardiometabolic risk profiles in adults. Reducing sedentary behaviour throughout the day and limiting TV-viewing and leisure-time computer use may have health benefits. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  20. Optical gamma thermometer

    DOEpatents

    Koster, Glen Peter; Xia, Hua; Lee, Boon Kwee

    2013-08-06

    An optical gamma thermometer includes a metal mass having a temperature proportional to a gamma flux within a core of a nuclear reactor, and an optical fiber cable for measuring the temperature of the heated metal mass. The temperature of the heated mass may be measured by using one or more fiber grating structures and/or by using scattering techniques, such as Raman, Brillouin, and the like. The optical gamma thermometer may be used in conjunction with a conventional reactor heat balance to calibrate the local power range monitors over their useful in-service life. The optical gamma thermometer occupies much less space within the in-core instrument tube and costs much less than the conventional gamma thermometer.

  1. In vitro Effects of Four Native Brazilian Medicinal Plants in CYP3A4 mRNA Gene Expression, Glutathione Levels, and P-Glycoprotein Activity.

    PubMed

    Mazzari, Andre L D A; Milton, Flora; Frangos, Samantha; Carvalho, Ana C B; Silveira, Dâmaris; de Assis Rocha Neves, Francisco; Prieto, Jose M

    2016-01-01

    Erythrina mulungu Benth. (Fabaceae), Cordia verbenacea A. DC. (Boraginaceae), Solanum paniculatum L. (Solanaceae) and Lippia sidoides Cham. (Verbenaceae) are medicinal plant species native to Brazil shortlisted by the Brazilian National Health System for future clinical use. However, nothing is known about their effects in metabolic and transporter proteins, which could potentially lead to herb-drug interactions (HDI). In this work, we assess non-toxic concentrations (100 μg/mL) of the plant infusions for their in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). Their mechanisms of action were further studied by measuring the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of γ-glutamyl transferase (GGT) in HepG2 cells. Our results show that P-gp activity was not affected in any case and that only Solanum paniculatum was able to significantly change CYP3A4 mRNA gene expression (twofold decrease, p < 0.05), this being correlated with an antagonist effect upon hPXR (EC50 = 0.38 mg/mL). Total intracellular glutathione levels were significantly depleted by exposure to Solanum paniculatum (-44%, p < 0.001), Lippia sidoides (-12%, p < 0.05) and Cordia verbenacea (-47%, p < 0.001). The latter plant extract was able to decrease GGT activity (-48%, p < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines may be able to cause disturbances to metabolic mechanisms in vitro. Although Erythrina mulungu appears safe in our tests, active pharmacovigilance is recommended for the other three species, especially in the case of Solanum paniculatum.

  2. Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats

    PubMed Central

    Bass, Virginia L.; Schladweiler, Mette C.; Nyska, Abraham; Thomas, Ronald F.; Miller, Desinia B.; Krantz, Todd; King, Charly; Gilmour, M. Ian; Ledbetter, Allen D.; Richards, Judy E.; Kodavanti, Urmila P.

    2016-01-01

    Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel + 80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500 μg/m3, 4 h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0 h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0>B100>B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants. PMID:26514782

  3. Comparative Hepatoprotective Effect of Vitamins A and E Against Gasoline Vapor Toxicity in Male and Female Rats

    PubMed Central

    Uboh, Friday Effiong; Ebong, Patrick E.; Umoh, Ime B.

    2009-01-01

    Background Plasma alanine transferase(ALT), aspartate transferase(AST), α-glutamyl transferase(GGT), and alkaline phosphatase(ALP) activities are known biomarkers in assessing hepatic functional integrity. A remarkable rise in the activities of these enzymes normally signifies hepatotoxicity of chemical agent(s) in the biological system. Exposure to 17.8 cm3h-1m-3 of PMS blend unleaded gasoline vapors (UGV) for 6 hr/day, 5 days/week for 20 weeks have been reported to cause hepatotoxicity in rats. Methods In this study, the comparative hepatoprotective effect of vitamins A (retinol) and E (α-tocopherol) against UGV-induced toxicity was assessed in male and female rats. Retinol and α-tocopherol at prophylactic dosage (400 and 200 IU/kg/day, respectively) were separately administered orally to the test rats concomitant with exposure to UGV in the last two weeks of the experiment. Results The results of this study indicated that exposure to UGV caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in male and female rats. Oral administration of prophylactic doses of retinol and α-tocopherol produced a significant decrease (P < 0.05) in the activities of these parameters in male and female test rats, compared with the non-treated test rats; but insignificant increase(P ≥ 0.05), compared with the control. However, the hepatoprotective effect of α-tocopherol was observed to be more potent than that of retinol. Conclusions The result of this study demonstrated that the hepatoprotective potency of α-tocopherol against gasoline vapors toxicity was higher than that of retinol in male and female rats, although the female gender of the animal model responded to treatment with both vitamins better than the males. Hence, the work suggested the beneficial effects of both vitamins against hepatotoxicity in individuals frequently exposed to gasoline vapors. PMID:27956974

  4. Infectious mononucleosis and hepatic function

    PubMed Central

    Zhang, Li; Zhou, Pingping; Meng, Zhaowei; Pang, Chongjie; Gong, Lu; Zhang, Qing; Jia, Qiyu; Song, Kun

    2018-01-01

    Abnormal hepatic function is common in infectious mononucleosis (IM). However, it remains unknown why increased transferase levels are more common than bilirubin abnormalities in IM. The current study aimed to investigate these associations in the Chinese population. A total of 95 patients with IM (47 males and 48 females) were enrolled in the current study, as well as 95 healthy controls. Patients were sorted by sex. A receiver operating characteristic (ROC) curve was used to determine cut-off values for IM diagnosis and prediction. Crude and adjusted odds ratios (OR) for IM were analyzed using binary logistic regression. It was determined that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) levels were significantly higher in patients with IM compared with controls; however, total bilirubin (TB) levels were significantly lower in patients with IM. ROCs demonstrated that, if ALT, AST and GGT concentrations were higher than, or if TB was lower than, cut-off values, they were predictive of IM. Binary logistic regression identified that the risk of IM in patients exhibiting high levels of transferases was significantly increased, particularly in males. Crude ORs in ALT quartile 4 were 21.667 and 10.111 for males and females, respectively and adjusted ORs were 38.054 and 9.882, respectively. A significant IM risk of IM was evident in patients with low bilirubin levels and females appeared to be particularly susceptible. For example, crude ORs in quartile 1 were 8.229 and 8.257 for males and females, respectively and adjusted ORs were 8.883 and 10.048, respectively. Therefore, the current study identified a positive association between transferase levels and IM and a negative association between TB and IM. Therefore, the results of the current study indicate that high transferases are suggestive of IM, particularly in males, whereas low TB is suggestive for IM, particularly in females. PMID:29456696

  5. Comparative clinical evaluation of Boerhavia diffusa root extract with standard Enalapril treatment in Canine chronic renal failure

    PubMed Central

    Oburai, Nethaji Lokeswar; Rao, V. Vaikunta; Bonath, Ram Babu Naik

    2015-01-01

    Background: Complementing herbal drugs with conservative modern treatment could improve renal condition in canine chronic renal failure (CRF). Objective: In this study, clinical evaluation of Boerhavia diffusa root extract was carried out in CRF in dogs in comparison with standard enalapril. Materials and Methods: A total of 20 dogs of mixed breeds suffering from CRF from 1 to 2 months were divided into two groups (n = 10) and treated as follows: Group I - Enalapril at 0.5 mg/kg p.o. once daily for 90 days + amoxicillin and cloxacillin at 25 mg/kg i.m. once daily for 1-week; Group II - B. diffusa root extract at 500 mg p.o per dog daily for 90 days. Both groups were maintained on a supportive fluid therapy. The data were analyzed using paired t-test and one-way ANOVA followed by Dunnett's post-hoc test. Results: CRF caused a significant (P < 0.05) increase in systolic and diastolic blood pressure, serum creatinine, urea nitrogen, sodium, potassium, phosphorus, urinary protein, alkaline phosphatase (ALP), and glutamyl transferase (GGT). A significant (P < 0.05) decrease in hemoglobin and total erythrocyte count (TEC) was also observed. Nephrosonography revealed indistinct corticomedullary junction, altered renal architecture, hyper-echoic cortex, medulla, and sunken kidneys. Both the treatments significantly (P < 0.05) reduced systolic and diastolic blood pressure by day 30. Serum Creatinine, urea nitrogen, phosphorus, urinary protein, ALP, and GGT showed significant (P < 0.05) reduction by day 60 in both the treatments. However, potassium levels were normalized only by B. diffusa root extract treatment by day 30. Both the treatments failed to show a significant improvement in nephrosonographic picture even after 90 days posttreatment. Conclusion: In conclusion, the efficacy of B. diffusa root extract was comparable to standard enalapril treatment of CRF in dogs. PMID:26604549

  6. In vitro Effects of Four Native Brazilian Medicinal Plants in CYP3A4 mRNA Gene Expression, Glutathione Levels, and P-Glycoprotein Activity

    PubMed Central

    Mazzari, Andre L. D. A.; Milton, Flora; Frangos, Samantha; Carvalho, Ana C. B.; Silveira, Dâmaris; de Assis Rocha Neves, Francisco; Prieto, Jose M.

    2016-01-01

    Erythrina mulungu Benth. (Fabaceae), Cordia verbenacea A. DC. (Boraginaceae), Solanum paniculatum L. (Solanaceae) and Lippia sidoides Cham. (Verbenaceae) are medicinal plant species native to Brazil shortlisted by the Brazilian National Health System for future clinical use. However, nothing is known about their effects in metabolic and transporter proteins, which could potentially lead to herb-drug interactions (HDI). In this work, we assess non-toxic concentrations (100 μg/mL) of the plant infusions for their in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). Their mechanisms of action were further studied by measuring the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of γ-glutamyl transferase (GGT) in HepG2 cells. Our results show that P-gp activity was not affected in any case and that only Solanum paniculatum was able to significantly change CYP3A4 mRNA gene expression (twofold decrease, p < 0.05), this being correlated with an antagonist effect upon hPXR (EC50 = 0.38 mg/mL). Total intracellular glutathione levels were significantly depleted by exposure to Solanum paniculatum (-44%, p < 0.001), Lippia sidoides (-12%, p < 0.05) and Cordia verbenacea (-47%, p < 0.001). The latter plant extract was able to decrease GGT activity (-48%, p < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines may be able to cause disturbances to metabolic mechanisms in vitro. Although Erythrina mulungu appears safe in our tests, active pharmacovigilance is recommended for the other three species, especially in the case of Solanum paniculatum. PMID:27594838

  7. Maresin conjugates in tissue regeneration biosynthesis enzymes in human macrophages.

    PubMed

    Dalli, Jesmond; Vlasakov, Iliyan; Riley, Ian R; Rodriguez, Ana R; Spur, Bernd W; Petasis, Nicos A; Chiang, Nan; Serhan, Charles N

    2016-10-25

    Macrophages are central in coordinating immune responses, tissue repair, and regeneration, with different subtypes being associated with inflammation-initiating and proresolving actions. We recently identified a family of macrophage-derived proresolving and tissue regenerative molecules coined maresin conjugates in tissue regeneration (MCTR). Herein, using lipid mediator profiling we identified MCTR in human serum, lymph nodes, and plasma and investigated MCTR biosynthetic pathways in human macrophages. With human recombinant enzymes, primary cells, and enantiomerically pure compounds we found that the synthetic maresin epoxide intermediate 13S,14S-eMaR (13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid) was converted to MCTR1 (13R-glutathionyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) by LTC 4 S and GSTM4. Incubation of human macrophages with LTC 4 S inhibitors blocked LTC 4 and increased resolvins and lipoxins. The conversion of MCTR1 to MCTR2 (13R-cysteinylglycinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) was catalyzed by γ-glutamyl transferase (GGT) in human macrophages. Biosynthesis of MCTR3 was mediated by dipeptidases that cleaved the cysteinyl-glycinyl bond of MCTR2 to give 13R-cysteinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid. Of note, both GSTM4 and GGT enzymes displayed higher affinity to 13S,14S-eMaR and MCTR1 compared with their classic substrates in the cysteinyl leukotriene metabolome. Together these results establish the MCTR biosynthetic pathway and provide mechanisms in tissue repair and regeneration.

  8. Implications of Gamma-Ray Transparency Constraints in Blazars: Minimum Distances and Gamma-Ray Collimation

    NASA Technical Reports Server (NTRS)

    Becker, Peter A.; Kafatos, Menas

    1995-01-01

    We develop a general expression for the gamma - gamma absorption coefficient, alpha(sub gamma(gamma)) for gamma-rays propagating in an arbitrary direction at an arbitrary point in space above an X-ray-emitting accretion disk. The X-ray intensity is assumed to vary as a power law in energy and radius between the outer disk radius, R(sub 0), and the inner radius, R(sub ms) which is the radius of marginal stability for a Schwarzschild black hole. We use our result for alpha(sub gamma(gamma)) to calculate the gamma - gamma optical depth, tau(sub gamma(gamma)) for gamma - rays created at height z and propagating at angle Phi relative to the disk axis, and we show that for Phi = 0 and z greater than or approx equal to R(sub 0), tau(sub gamma(gamma)) proportional to Epsilon(sup alpha)z(sup -2(alpha) - 3), where alpha is the X-ray spectral index and Epsilon is the gamma - ray energy. As an application, we use our formalism to compute the minimum distance between the central black hole and the site of production of the gamma-rays detected by EGRET during the 1991 June flare of 3C 279. In order to obtain an upper limit, we assume that all of the X-rays observed contemporaneously by Ginga were emitted by the disk. Our results suggest that the observed gamma - rays may have originated within less than or approx equal to 45 GM/sq c from a black hole of mass greater than or approx equal to 10(exp 9) solar mass, perhaps in active plasma located above the central funnel of the accretion disk. This raises the possibility of establishing a direct connection between the production of the observed gamma - rays and the accretion of material onto the black hole. We also consider the variation of the optical depth as a function of the angle of propagation Phi. Our results indicate that the "focusing" of the gamma - rays along the disk axis due to pair production is strong enough to explain the observed degree of alignment in blazar sources. If the gamma - rays are produced isotropically

  9. Design and performance of the GAMMA-400 gamma-ray telescope for dark matter searches

    NASA Astrophysics Data System (ADS)

    Galper, A. M.; Adriani, O.; Aptekar, R. L.; Arkhangelskaja, I. V.; Arkhangelskiy, A. I.; Boezio, M.; Bonvicini, V.; Boyarchuk, K. A.; Fradkin, M. I.; Gusakov, Yu. V.; Kaplin, V. A.; Kachanov, V. A.; Kheymits, M. D.; Leonov, A. A.; Longo, F.; Mazets, E. P.; Maestro, P.; Marrocchesi, P.; Mereminskiy, I. A.; Mikhailov, V. V.; Moiseev, A. A.; Mocchiutti, E.; Mori, N.; Moskalenko, I. V.; Naumov, P. Yu.; Papini, P.; Picozza, P.; Rodin, V. G.; Runtso, M. F.; Sparvoli, R.; Spillantini, P.; Suchkov, S. I.; Tavani, M.; Topchiev, N. P.; Vacchi, A.; Vannuccini, E.; Yurkin, Yu. T.; Zampa, N.; Zverev, V. G.; Zirakashvili, V. N.

    2013-02-01

    The GAMMA-400 gamma-ray telescope is designed to measure the fluxes of gamma-rays and cosmic-ray electrons + positrons, which can be produced by annihilation or decay of the dark matter particles, as well as to survey the celestial sphere in order to study point and extended sources of gamma-rays, measure energy spectra of Galactic and extragalactic diffuse gamma-ray emission, gamma-ray bursts, and gamma-ray emission from the Sun. GAMMA-400 covers the energy range from 100 MeV to 3000 GeV. Its angular resolution is ~0.01° (Eγ > 100 GeV), the energy resolution ~1% (Eγ > 10 GeV), and the proton rejection factor ~106. GAMMA-400 will be installed on the Russian space platform Navigator. The beginning of observations is planned for 2018.

  10. Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site.

    PubMed Central

    Liaw, S. H.; Kuo, I.; Eisenberg, D.

    1995-01-01

    Glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and glutamate to yield glutamine, ADP, and inorganic phosphate in the presence of divalent cations. Bacterial GS is an enzyme of 12 identical subunits, arranged in two rings of 6, with the active site between each pair of subunits in a ring. In earlier work, we have reported the locations within the funnel-shaped active site of the substrates glutamate and ATP and of the two divalent cations, but the site for ammonia (or ammonium) has remained elusive. Here we report the discovery by X-ray crystallography of a binding site on GS for monovalent cations, Tl+ and Cs+, which is probably the binding site for the substrate ammonium ion. Fourier difference maps show the following. (1) Tl+ and Cs+ bind at essentially the same site, with ligands being Glu 212, Tyr 179, Asp 50', Ser 53' of the adjacent subunit, and the substrate glutamate. From its position adjacent to the substrate glutamate and the cofactor ADP, we propose that this monovalent cation site is the substrate ammonium ion binding site. This proposal is supported by enzyme kinetics. Our kinetic measurements show that Tl+, Cs+, and NH4+ are competitive inhibitors to NH2OH in the gamma-glutamyl transfer reaction. (2) GS is a trimetallic enzyme containing two divalent cation sites (n1, n2) and one monovalent cation site per subunit. These three closely spaced ions are all at the active site: the distance between n1 and n2 is 6 A, between n1 and Tl+ is 4 A, and between n2 and Tl+ is 7 A. Glu 212 and the substrate glutamate are bridging ligands for the n1 ion and Tl+. (3) The presence of a monovalent cation in this site may enhance the structural stability of GS, because of its effect of balancing the negative charges of the substrate glutamate and its ligands and because of strengthening the "side-to-side" intersubunit interaction through the cation-protein bonding. (4) The presence of the cofactor ADP increases the Tl+ binding to GS

  11. Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

    PubMed Central

    Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

    1992-01-01

    The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo. PMID:1534001

  12. Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

    PubMed

    Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

    1992-04-01

    The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.

  13. Gamma Knife

    MedlinePlus

    ... equipment? How is safety ensured? What is this equipment used for? The Gamma Knife® and its associated ... in size. top of page How does the equipment work? The Gamma Knife® utilizes a technique called ...

  14. [Hereditary fructose intolerance (HFI) as cause of isolated gamma GT rise in a 5-year old boy with hepatomegaly].

    PubMed

    Wössmann, W; Wiemann, J; Körber, F; Gortner, L

    2000-01-01

    The diagnosis of HFI is easily missed during childhood. It should be suspected in children presenting with hepatomegaly and an isolated increase in GGT. A carefully taken nutritional history forms the basis of the diagnosis of HFI which can be confirmed by molecular analysis with a sensitivity of > 95%. I.v. fructose tolerance tests and liver biopsies often can be omitted.

  15. Gamma-400 Science Objectives Built on the Current HE Gamma-Ray and CR Results

    NASA Technical Reports Server (NTRS)

    Moiseev, Alexander; Mitchell, John; Thompson, David

    2012-01-01

    The main scientific interest of the Russian Gamma-400 team: Observe gamma-rays above approximately 50 GeV with excellent energy and angular resolution with the goals of: (1) Studying the fine spectral structure of the isotropic high-energy gamma-radiation, (2) Attempting to identify the many still-unidentified Fermi-LAT gamma-ray sources. Gamma-400 will likely be the only space-based gamma-ray observatory operating at the end of the decade. In our proposed Gamma-400-LE version, it will substantially improve upon the capabilities of Fermi LAT and AGILE in both LE and HE energy range. Measuring gamma-rays from approx 20 MeV to approx 1 TeV for at least 7 years, Gamma-400-LE will address the topics of dark matter, cosmic ray origin and propagation, neutron stars, flaring pulsars, black holes, AGNs, GRBs, and actively participate in multiwavelength campaigns.

  16. Characterization of toxicosis in sheep dosed with blossoms of sacahuiste (Nolina microcarpa).

    PubMed

    Rankins, D L; Smith, G S; Ross, T T; Caton, J S; Kloppenburg, P

    1993-09-01

    To characterize more fully sacahuiste (Nolina microcarpa Watson) toxicosis in sheep and to evaluate benefits of supplemental Zn, sheep were dosed intraruminally with sacahuiste blossoms. In Trial 1, eight fine-wool sheep (47 +/- 2 kg BW) were fed alfalfa hay at 1% of BW daily and dosed intraruminally with inflorescences amounting to 1% of BW daily, in three portions per day, for 10 d. Four sheep were dosed intraruminally with aqueous ZnSO4 (30 mg of Zn/kg BW) daily for 3 d before initial sacahuiste dosing and on alternate days thereafter, and four sheep were untreated with Zn. Toxicosis was evident within 24 h after initial sacahuiste dosage, involving inappetence, depression, hypokalemia, hypophosphatemia, hyperbilirubinemia, and elevated serum enzymes (alkaline phosphatase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transpeptidase). One sheep (untreated with Zn) died on d 3. Aqueous ZnSO4 alleviated inappetence and suppressed elevation of serum urea N and creatinine but did not suppress other changes in serum clinical profiles. In Trial 2, sacahuiste inflorescences were ruminally dosed into 12 fine-wool wethers (29 +/- 2 kg BW) in amounts equalling 0, .25, .50, .75% of BW per day, and chopped alfalfa hay was provided at 1.75% of BW per day for 14 d. Sacahuiste inflorescenses dosed at .75% of BW elicited severe toxicosis within 24 h, and dosage at .50 or .25% of BW per day increased (P = .12) serum bilirubin. Ruminal fluid pH, mean particle retention time, and particulate passage rate were not affected (P > .10) by sacahuiste, but ruminal fluid passage rate increased 1.6-fold (P < .10) and ruminal fluid volume decreased by 60% (P < .10) in sheep given inflorescenses amounting to .50% of BW daily. Sacahuiste inflorescenses dosed intraruminally at .75% of BW per day elicited ruminal impaction with severe hepatotoxicosis, and dosages amounting to .50% or .25% of BW per day caused similar trends.

  17. Clinical impact of non-organ-specific autoantibodies on the response to combined antiviral treatment in patients with hepatitis C.

    PubMed

    Muratori, Paolo; Muratori, Luigi; Guidi, Marcello; Granito, Alessandro; Susca, Micaela; Lenzi, Marco; Bianchi, Francesco B

    2005-02-15

    Hepatitis C virus (HCV)-related chronic hepatitis is frequently associated with non-organ-specific autoantibodies (NOSAs), but available data about the relationship between NOSA positivity and the effect of antiviral therapy in persons with hepatitis C are few and controversial. Our aim was to evaluate the impact of NOSA positivity on the outcome of combined antiviral therapy in HCV-positive patients. A total of 143 consecutive adult patients with hepatitis C were studied. Antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomal antibody type 1 (LKM1) were detected by indirect immunofluorescence. All patients were treatment naive and received combined antiviral therapy (interferon [IFN]-ribavirin) after enrollment in the study. Patients were classified as nonresponders if HCV RNA was detectable after 6 months of therapy, as relapsers if abnormal transaminase levels and reactivation of HCV replication were observed after the end of treatment, and as long-term responders if transaminase levels were persistently normal and HCV RNA was undetectable 6 months after the end of treatment. Thirty-seven patients (25%) were NOSA positive (SMA was detected in 19 patients, ANA in 10, ANA and SMA in 4, LKM1 in 3, and SMA and LKM1 in 1). The prevalence of long-term response was similar between NOSA-positive patients and NOSA-negative patients (48.6% vs. 56.6%; P=not significant). Compared with HCV genotype 1 (HCV-1), HCV genotypes other than 1 were more often associated with long-term response among NOSA-positive patients (93.3% vs. 30%; P=.0017). The overall rate of long-term response, irrespective of NOSA status, was 54.5%. Detection of HCV-1 and elevated gamma-glutamyl transpeptidase serum levels were independent negative prognostic factors of treatment response (P=.007 and P=.026, respectively). Combined antiviral treatment (IFN-ribavirin) is safe and effective in NOSA-positive patients with hepatitis C, even if long-term response is

  18. Non-alcoholic fatty liver disease in diabetics--prevalence and predictive factors in a multiracial hospital clinic population in Malaysia.

    PubMed

    Chan, Wah-Kheong; Tan, Alexander Tong-Boon; Vethakkan, Shireene Ratna; Tah, Pei-Chien; Vijayananthan, Anushya; Goh, Khean-Lee

    2013-08-01

    There is currently no published study comparing prevalence of non-alcoholic fatty liver disease (NAFLD) and associated factors among diabetics of different ethnicity in the Asia-Pacific region. Cross-sectional study of consecutive patients in the Diabetic Clinic in University of Malaya Medical Centre. The Global Physical Activity Questionnaire and a semiquantitative food-frequency questionnaire were used to assess physical activity and dietary intake, respectively. Diagnosis of NAFLD was ultrasound-based and following exclusion of significant alcohol intake. Data for 399 patients were analyzed (mean age 62.3 ± 10.5 years, 43.1% men). The racial distribution was Chinese 43.6%, Indian 33.1%, Malay 22.3%, and others 1.0%. The prevalence of NAFLD was 49.6%. On univariate analysis, factors associated with NAFLD were age < 65 years, race, obesity, central obesity, glycated hemoglobin ≥ 7.0%, and elevated serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels. Patients with low physical activity were more likely to have NAFLD (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.06-2.63, P = 0.020). The prevalence of NAFLD was highest among Malays (60.7%), followed by Indians (51.5%), and lowest among Chinese (42.0%) consistent with higher prevalence of central obesity and higher percentage calorie intake from fat in the former groups of patients. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR = 2.20, 95% CI = 1.29-3.75, P = 0.004) and elevated serum ALT level (OR = 1.98, 95% CI = 1.21-3.25, P = 0.007). NAFLD was seen in half of a cohort of diabetic patients and was independently associated with central obesity and elevated serum ALT level. Prevalence of NAFLD was different and paralleled the difference in prevalence of central obesity and in percentage calorie intake from fat among the different ethnic groups. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia

  19. Alcoholic Ketosis: Prevalence, Determinants, and Ketohepatitis in Japanese Alcoholic Men.

    PubMed

    Yokoyama, Akira; Yokoyama, Tetsuji; Mizukami, Takeshi; Matsui, Toshifumi; Shiraishi, Koichi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

    2014-11-01

    Alcoholic ketosis and ketoacidosis are metabolic abnormalities often diagnosed in alcoholics in emergency departments. We attempted to identify determinants or factors associated with alcoholic ketosis. The subjects of this cross-sectional survey were 1588 Japanese alcoholic men (≥40 years) who came to an addiction center within 14 days of their last drink. The results of the dipstick urinalyses revealed a prevalence of ketosis of 34.0% (±, 21.5%; +, 8.9%; and 2+/3+; 3.6%) in the alcoholics. Higher urine ketone levels were associated with higher serum total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyl transpeptidase levels. A multivariate analysis by the proportional odds model showed that the odds ratio (95% confidence interval) for an increase in ketosis by one category was 0.94 (0.84-1.06) per 10-year increase in age, 0.93 (0.89-0.97) per 1-day increase in interval since the last drink, 1.78 (1.41-2.26) in the presence of slow-metabolizing alcohol dehydrogenase-1B (ADH1B*1/*1), 1.61 (1.10-2.36) and 1.30 (1.03-1.65) when the beverage of choice was whiskey and shochu, respectively (distilled no-carbohydrate beverages vs. the other beverages), 2.05 (1.27-3.32) in the presence of hypoglycemia <80 mg/dl, 0.91 (0.88-0.94) per 1-kg/m(2) increase in body mass index (BMI), 1.09 (1.00-1.18) per +10 cigarettes smoked, and 2.78 (2.05-3.75) when the serum total bilirubin level was ≥2.0 mg/dl, and 1.97 (1.47-2.66) when the serum AST level was ≥200 IU/l. Ketosis was a very common complication and frequently accompanied by alcoholic liver injury in our Japanese male alcoholic population, in which ADH1B*1/*1 genotype, consumption of whiskey or shochu, hypoglycemia, lower BMI and smoking were significant determinants of the development of ketosis. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  20. Comparative evaluation of GPR versus APRI and FIB-4 in predicting different levels of liver fibrosis of chronic hepatitis B.

    PubMed

    Liu, D-P; Lu, W; Zhang, Z-Q; Wang, Y-B; Ding, R-R; Zhou, X-L; Huang, D; Li, X-F

    2018-05-01

    It is of great significance to develop and evaluate noninvasive indexes predicting the level of liver fibrosis. The aim of this study was to comparatively evaluate gamma-glutamyl transpeptidase-to-platelet ratio (GPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on 4 factors (FIB-4) in predicting different levels of liver fibrosis of chronic hepatitis B (CHB) within the framework of HBeAg-positive and HBeAg-negative patients. A total of 1157 HBeAg-positive and 859 HBeAg-negative CHB patients were enrolled, among whom the pathological stage ≥S2, ≥S3, ≥S4 were defined as significant fibrosis, extensive fibrosis and cirrhosis, respectively. Receiver operating characteristic (ROC) curves were used to evaluate the performance of GPR, APRI and FIB-4 in predicting different levels of liver fibrosis. In HBeAg-positive patients, the area under ROC curves (AUROCs) of GPR in predicting extensive fibrosis and cirrhosis were both significantly larger than those of APRI (P = .0001 and P < .0001). In HBeAg-negative patients, the AUROCs of GPR in predicting significant fibrosis and cirrhosis were significantly larger than those of FIB-4 (P = .0006 and P = .0041). The AUROC of GPR in predicting extensive fibrosis was significantly larger than that of APRI and FIB-4 (P = .0320 and P = .0018). Using a cut-off of GPR > 0.500 as standard, the sensitivities and specificities of GPR in predicting significant fibrosis in HBeAg-positive patients were 59.6% and 81.2%, and for cirrhosis 80.9% and 63.8%, respectively; and those of HBeAg-negative patients were 60.3% and 78.3%, 84.5% and 66.1%, respectively. Regardless of HBeAg-positive or HBeAg-negative status, GPR had the best performance in predicting different levels of liver fibrosis. © 2017 John Wiley & Sons Ltd.