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Sample records for glutamyl transpeptidase ggt

  1. Gamma-glutamyl transpeptidase (GGT) blood test

    Science.gov (United States)

    ... 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 ...

  2. GGT (Gamma-Glutamyl Transferase) Test

    Science.gov (United States)

    ... in most diseases that cause damage to the liver or bile ducts. This test measures the level of GGT in ... Get Tested? When you have symptoms of a liver or bile duct disorder or as follow up when you have ...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  5. Covalent Immobilization of Bacillus licheniformis γ-Glutamyl Transpeptidase on Aldehyde-Functionalized Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Meng-Chun Chi

    2013-02-01

    Full Text Available This work presents the synthesis and use of surface-modified iron oxide nanoparticles for the covalent immobilization of Bacillus licheniformis γ-glutamyl transpeptidase (BlGGT. Magnetic nanoparticles were prepared by an alkaline solution of divalent and trivalent iron ions, and they were subsequently treated with 3-aminopropyltriethoxysilane (APES to obtain the aminosilane-coated nanoparticles. The functional group on the particle surface and the amino group of BlGGT was then cross-linked using glutaraldehyde as the coupling reagent. The loading capacity of the prepared nanoparticles for BlGGT was 34.2 mg/g support, corresponding to 52.4% recovery of the initial activity. Monographs of transmission electron microscopy revealed that the synthesized nanoparticles had a mean diameter of 15.1 ± 3.7 nm, and the covalent cross-linking of the enzyme did not significantly change their particle size. Fourier transform infrared spectroscopy confirmed the immobilization of BlGGT on the magnetic nanoparticles. The chemical and kinetic behaviors of immobilized BlGGT are mostly consistent with those of the free enzyme. The immobilized enzyme could be recycled ten times with 36.2% retention of the initial activity and had a comparable stability respective to free enzyme during the storage period of 30 days. Collectively, the straightforward synthesis of aldehyde-functionalized nanoparticles and the efficiency of enzyme immobilization offer wide perspectives for the practical use of surface-bound BlGGT.

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

    Science.gov (United States)

    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.

  7. Evolving transpeptidase and hydrolytic variants of γ-glutamyl transpeptidase from Bacillus licheniformis by targeted mutations of conserved residue Arg109 and their biotechnological relevance.

    Science.gov (United States)

    Bindal, Shruti; Sharma, Sujata; Singh, Tej P; Gupta, Rani

    2017-05-10

    γ-Glutamyl transpeptidase (GGT) catalyzes the transfer of the γ-glutamyl moiety from donor compounds such as l-glutamine (Gln) and glutathione (GSH) to an acceptor. During the biosynthesis of various γ-glutamyl-containing compounds using GGT enzyme, auto-transpeptidation reaction leads to the formation of unwanted byproducts. Therefore, in order to alter the auto-transpeptidase activity of the GGT enzyme, the binding affinity of Gln should be modified. Structural studies of the Bacillus licheniformis GGT (BlGT) complexed with the glutamic acid has shown that glutamic acid has strong ionic interactions through its α-carboxlic group with the guanidine moiety of Arg109. This interaction appears to be an important contributor for the binding affinity of Gln. In view of this, six mutants of Bacillus licheniformis ER15 GGT (BlGGT) viz. Arg109Lys, Arg109Ser, Arg109Met, Arg109Leu, Arg109Glu and Arg109Phe were prepared. As seen from the structure of BlGT, the mutation of Arg109 to Lys109 may reduce the affinity for Gln to some extent, whereas the other mutations are expected to lower the affinity much more. Biophysical characterization and functional studies revealed that Arg109Lys mutant has increased transpeptidation activity and catalytic efficiency than the other mutants. The Arg109Lys mutant showed high conversion rates for l-theanine synthesis as well. Moreover, the Arg109Met mutant showed increased hydrolytic activity as it completely altered the binding of Gln at the active site. Also, the salt stability of the enzyme was significantly improved on replacing Arg109 by Met109 which is required for hydrolytic applications of GGTs in food industries. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Metabolic syndrome is directly associated with gamma glutamyl transpeptidase elevation in Japanese women

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Sakugawa; Fukunori Kin jo; Atsushi Saito; Tomofumi Nakayoshi; Kasen Kobashigawa; Hiroki Nakasone; Yuko Kawakami; Tsuyoshi Yamashiro; Tatsuji Maeshiro; Ko Tomimori; Satoru Miyagi

    2004-01-01

    AIM: This study aimed to determine whether metabolic syndrome is directly or indirectly, through fatty liver, associated with elevated gamma-glutamyl transpeptidase (GGT) levels in Japanese women.METHODS: From 4 366 women who received their annual health check-up, 4 211 women were selected for analysis.All 4 211 women were negative for both hepatitis B surface antigen and antibody to hepatitis C virus. Clinical and biochemical variables were examined by using univariate and multivariate analysis.RESULTS: A raised GGT level (>68 IU/L) was seen in 258 (6.1%) of the 4 211 women. In univariate analysis, all variables examined (age, body mass index, blood pressure,hemoglobin concentration, fasting blood glucose,glycosylated hemoglobin A1c, cholesterol, triglyceride, and uric acid) were associated with the elevated GGT level,whereas in multivariate analysis, four variables (age ≥ 50 yr,hemoglobin ≥14 g/dL, triglyceride ≥ 150 mg/dL, and presence of diabetes) were significantly and independently associated with raised GGT level. Clinical variables predicting the presence of ultrasonographic evidence of fatty liver were also examined by multivariate analysis; four variables were associated with the presence of fatty liver: BMI ≥ 25 kg/m2,hemoglobin ≥ 14 g/dL, triglyceride≥150 mg/dL, and uric acid≥ 7 mg/dL. There was no significant association between the raised GGT level and the presence of fatty liver.Hypertriglyceridemia was significantly and independently associated with both the raised GGT level and the presence of fatty liver.CONCLUSION: Metabolic syndrome seemed to be directly,not indirectly through fatty liver, associated with the raised GGT level in Japanese women.

  9. The effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic gamma-glutamyl transpeptidase.

    Science.gov (United States)

    Kawamoto, T; Matsuno, K; Kayama, F; Arashidani, K; Yoshikawa, M; Kodama, Y

    1992-11-22

    In this paper, we determined whether ethylene glycol monomethyl ether (EGME) and diethylene glycol monomethyl ether (diEGME) induce hepatic gamma-glutamyl transpeptidase activity. Male adult Wistar rats weighing 220 g were used as experimental animals. EGME (100, 300 mg/kg per day) and diEGME (500, 1000, 2000 mg/kg per day) were administered by gavage for 1, 2 or 5 days or 4 weeks. In the 4-week study, experimental animals were administered EGME or diEGME once a day orally, 5 days/week. EGME treatment increased the serum gamma-glutamyl transpeptidase (GGT) level significantly, however, diEGME did not. The activities of three other enzymes (SGOT, SGPT and ALP) in serum were not altered by EGME or diEGME treatment and thus there was no biochemical indices of hepatic damage by EGME or diEGME. EGME treatment increased the GGT activities in the liver and lungs. Of the organs examined, the induction of GGT was the greatest in the liver. The inducibility in the liver was 216% for the 5-day treatment and 460% for the 4-week treatment. A dose-dependent increase of hepatic microsomal GGT activity by EGME was observed. On the other hand, renal GGT activities were declined to 72% and 60% of control by the 5-day and 4-week EGME treatments, respectively. DiEGME did not affect the GGT activities in any of the tissues except those of the brain. In the histochemical study, most hepatocytes at the periportal zones were stained with GGT staining after the 4-week treatment. However, the hepatocytes at the central zones were negative.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels: Evidence for correlated genetic effects

    NARCIS (Netherlands)

    van Beek, J.H.D.A.; de Moor, M.H.M.; Geels, L.M.; Sinke, M.R.T.; de Geus, E.J.C.; Lubke, G.H.; Kluft, C.; Neuteboom, J.; Vink, J.M.; Willemsen, G.; Boomsma, D.I.

    2014-01-01

    Background: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT

  13. Anabolic Androgen-induced Intrahepatic Cholestasis Presented With Normal AND#947;-Glutamyl-Transpeptidase

    Directory of Open Access Journals (Sweden)

    Savvoula Savvidou

    2014-04-01

    A case report of a young male with remarkable jaundice due to acute anabolic androgen-induced cholestasis is presented. Interestingly, and #947;-glutamyl transpeptidase remained normal throughout the patient's diagnostic workup. Histopathology was indicative of pure, and ldquo;bland and rdquo; intrahepatic cholestasis with minimal inflammation but significant fibrosis. The patient was successfully treated with ursodeoxycholic acid and glucocorticosteroids. The significance of normal and #947;-glutamyl transpeptidase along with the histopathological findings and the possible pathophysiological mechanisms are finally discussed. [J Interdiscipl Histopathol 2014; 2(2.000: 98-103

  14. Original Paper Upregulation of gamma-glutamyl-transpeptidase ...

    African Journals Online (AJOL)

    The objective of the study was to determine a possible relationship between. GGT, uric acid and the ...... photometric method for determination of .... Studies on Association Between Copper. Excess,. Zinc. Deficiency and TP53 Mutations in.

  15. A gonococcal homologue of meningococcal γ-glutamyl transpeptidase gene is a new type of bacterial pseudogene that is transcriptionally active but phenotypically silent

    Directory of Open Access Journals (Sweden)

    Watanabe Haruo

    2005-10-01

    Full Text Available Abstract Background It has been speculated that the γ-glutamyl transpeptidase (ggt gene is present only in Neisseria meningitidis and not among related species such as Neisseria gonorrhoeae and Neisseria lactamica, because N. meningitidis is the only bacterium with GGT activity. However, nucleotide sequences highly homologous to the meningococcal ggt gene were found in the genomes of N. gonorrhoeae isolates. Results The gonococcal homologue (ggt gonococcal homologue; ggh was analyzed. The nucleotide sequence of the ggh gene was approximately 95 % identical to that of the meningococcal ggt gene. An open reading frame in the ggh gene was disrupted by an ochre mutation and frameshift mutations induced by a 7-base deletion, but the amino acid sequences deduced from the artificially corrected ggh nucleotide sequences were approximately 97 % identical to that of the meningococcal ggt gene. The analyses of the sequences flanking the ggt and ggh genes revealed that both genes were localized in a common DNA region containing the fbp-ggt (or ggh-glyA-opcA-dedA-abcZ gene cluster. The expression of the ggh RNA could be detected by dot blot, RT-PCR and primer extension analyses. Moreover, the truncated form of ggh-translational product was also found in some of the gonococcal isolates. Conclusion This study has shown that the gonococcal ggh gene is a pseudogene of the meningococcal ggt gene, which can also be designated as Ψggt. The gonococcal ggh (Ψggt gene is the first identified bacterial pseudogene that is transcriptionally active but phenotypically silent.

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

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    Sajid Mohammed

    2006-05-01

    Full Text Available Background 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. Results 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 γ-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. γ-Glutamyl transpeptidases are type II integral membrane proteins; however, the identified AG γ-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 γ-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. Conclusion We have applied biochemical approaches, not used

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

    Science.gov (United States)

    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

  18. High Resolution X-ray Diffraction Dataset for Bacillus licheniformis Gamma Glutamyl Transpeptidase-acivicin complex: SUMO-Tag Renders High Expression and Solubility.

    Science.gov (United States)

    Kumari, Shobha; Pal, Ravi Kant; Gupta, Rani; Goel, Manisha

    2017-02-01

    Gamma glutamyl transpeptidase, (GGT) is a ubiquitous protein which plays a central role in glutathione metabolism and has myriad clinical implications. It has been shown to be a virulence factor for pathogenic bacteria, inhibition of which results in reduced colonization potential. However, existing inhibitors are effective but toxic and therefore search is on for novel inhibitors, which makes it imperative to understand the interactions of various inhibitors with the protein in substantial detail. High resolution structures of protein bound to different inhibitors can serve this purpose. Gamma glutamyl transpeptidase from Bacillus licheniformis is one of the model systems that have been used to understand the structure-function correlation of the protein. The structures of the native protein (PDB code 4OTT), of its complex with glutamate (PDB code 4OTU) and that of its precursor mimic (PDB code 4Y23) are available, although at moderate/low resolution. In the present study, we are reporting the preliminary analysis of, high resolution X-ray diffraction data collected for the co-crystals of B. licheniformis, Gamma glutamyl transpeptidase, with its inhibitor, Acivicin. Crystals belong to the orthorhombic space group P2 1 2 1 2 1 and diffract X-ray to 1.45 Å resolution. This is the highest resolution data reported for all GGT structures available till now. The use of SUMO fused expression system enhanced yield of the target protein in the soluble fraction, facilitating recovery of protein with high purity. The preliminary analysis of this data set shows clear density for the inhibitor, acivicin, in the protein active site.

  19. Effect of mercuric chloride intoxication on urinary. gamma. -glutamyl transpeptidase excretion in the sheep

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, F D

    1976-01-01

    The activity of the enzyme ..gamma..-glutamyl transpeptidase (..gamma..-GT) was measured in the urine of sheep. In clinically normal animals the mean value was 6.3 +/- 0.6 mU/ml. In sheep with kidney damage induced by the administration of mercuric chloride there were marked increases in urinary concentrations of ..gamma..-GT, in some cases values in excess of 1000 mU/ml were recorded. This enzyme may be of value in the diagnosis of certain forms of renal disease. 13 references, 1 figure, 1 table.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. Identification of a highly reactive threonine residue at the active site of γ-glutamyl transpeptidase

    International Nuclear Information System (INIS)

    Stole, E.; Seddon, A.P.; Wellner, D.; Meister, A.

    1990-01-01

    γ-Glutamyl transpeptidase an enzyme of major importance in glutathione metabolism, was inactivated by treating it with L-(αS,5S)-α-amino-3-chloro-4,5-dihydro-5-[3- 14 C]isoxazoleacetic acid. This selective reagent binds stoichiometrically to the enzyme; more than 90% of the label was bound to its light subunit. Enzymatic digestion of the light subunit gave a 14 C-labeled peptide that corresponds to amino acid residues 517-527 of the enzyme and two incomplete digestion products that contain this labeled peptide moiety. The radioactivity associated with this peptide was released with threonine-523 during sequencing by the automated gas-phase Edman method. The light subunit contains 14 other threonine residues and a total of 19 serine residues; these were not labeled. Threonine-523 is situated in the enzyme in an environment that greatly increases its reactivity, indicating that other amino acid residues of the enzyme must also participate in the active-site chemistry of the enzyme

  3. Heterogeneous nucleation helps the search for initial crystallization conditions of γ-glutamyl transpeptidase from Bacillus licheniformis

    International Nuclear Information System (INIS)

    Lin, Long-Liu; Merlino, Antonello

    2013-01-01

    An additional example in which heterogeneous nucleation has helped in the search for crystallization conditions of a protein is reported. Optimization of the crystallization conditions led to the formation of single crystals of γ-glutamyl transpeptidase from B. licheniformis that diffracted to about 3.0 Å resolution. Here, the crystallization and preliminary X-ray diffraction studies of Bacillus licheniformis γ-glutamyl transpeptidase (BlGT) are reported. The serendipitous finding of heterogeneous nucleants in the initial experiments provided the first crystallization conditions for the protein. Crystals were grown by hanging-drop vapour diffusion using a precipitant solution consisting of 20%(w/v) PEG 3350, 0.2 M magnesium chloride hexahydrate, 0.1 M Tris–HCl pH 8.2. The protein crystallized in the orthorhombic space group P2 1 2 1 2 1 , with one heterodimer per asymmetric unit and unit-cell parameters a = 60.90, b = 61.97, c = 148.24 Å. The BlGT crystals diffracted to 2.95 Å resolution

  4. Effects of irradiation and storage on the gamma-glutamyl transpeptidase activity of garlic bulbs cv 'Red'

    International Nuclear Information System (INIS)

    Ceci, L.N.; Curzio, O.A.; Pomilio, A.B.

    1992-01-01

    The effects of 50 Gy gamma-irradiation 30 days after harvest on gamma-glutamyl transpeptidase (GTP) activity (the first enzyme in the catabolism of gamma-glutamyl peptides) of garlic bulbs of 'Red' during storage for 300 days were evaluated. GTP activity was determined by spectrophotometry using gamma-glutamyl-p-nitroanilide as exogenous substrate, and was correlated with parameters related to the metabolic-respiratory activity, such as sprouting index in control bulbs, and cumulative weight losses (CWL) and non-enzymic or control pyruvate (CP: metabolite of the respiratory chain) in irradiated and control bulbs. GTP activity was also correlated with flavour parameters, such as enzymic pyruvate (EP; metabolite of the reaction of alliinase and sulphur amino acids in crushed garlic) and primary sulphur compounds. From these results, three storage stages are suggested: (i) the internal dormancy period, (ii) the first post-dormant stage, and (iii) the second post-dormant stage. During the first 90 days of storage (first stage) all the parameters remained nearly constant in the controls, while GTP activity and CP content increased in irradiated garlic because of radioinduced metabolic-respiratory activation. From 90 to 180 days of storage (second stage) the correlation between the increases of GTP and EP in irradiated garlic and controls was due to the action of GTP on gamma-glutamyl peptides that finally released substrates of alliinase. Both enzymes increased EP contact, which was higher in irradiated garlic (major flavour enhancement) than in controls. After 180 days of storage (third stage) EP and primary sulphur compounds decreased in irradiated garlic and in the controls. while GTP, CWL and CP kept increasing in both samples with lower rates of increase in irradiated garlic. These increases were related to metabolic activation. reserve exhaustion and finally rotting. Therefore, irradiated garlic was of better quality at the end of storage

  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

    OpenAIRE

    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

    2017-01-01

    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-lymphocy...

  6. Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study.

    Science.gov (United States)

    Ceriotti, Ferruccio; Henny, Joseph; Queraltó, Josep; Ziyu, Shen; Özarda, Yeşim; Chen, Baorong; Boyd, James C; Panteghini, Mauro

    2010-11-01

    Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC-recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18-85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 μkat/L), allowing a single RI of 11-34 U/L (0.18-0.57 μkat/L) to be defined. Interregional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8-41 U/L (0.13-0.68 μkat/L) for females and 9-59 U/L (0.15-0.99 μkat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6-40 U/L (0.11-0.66 μkat/L) for females and 12-68 U/L (0.20- 1.13 μkat/L) for males, respectively. For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is

  7. 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.

    Science.gov (United States)

    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.

  8. Atividade da gama glutamil transpeptidase urinária, dosagens séricas de uréia e creatinina como meios diagnósticos auxiliares na nefrotoxicidade induzida por aminoglicosídeo em cães Urinary gamma glutamyl transpeptidase activity, urinalysis, bun and creatinine serum dosages as a auxiliary diagnostic mean in dogs nephrotoxicity induced by aminoglycosides

    Directory of Open Access Journals (Sweden)

    Carla Rosane de Aguiar Hennemann

    1997-06-01

    Full Text Available Foram utilizados 11 cães, hígidos, com idade entre 1 e 5 anos. Inicialmente procedeu-se à determinação dos valores basais através de cinco colheitas diárias de urina e sangue, e realizou-se a urinálise, determinação da atividade da gama glutamil transpeptidase urinária, dosagens sérica de uréia e creatinina. A nefrotoxicidade foi induzida com a utilização de10mg/kg de gentamicina, 3 vezes ao dia, durante 14 dias. As colheitas de urina foram realizadas a cada 24 hors e o sangue foi colhido a cada 48 horas, durante 14 dias. Após este período os cães foram submetidos à eutanásia, procedendo-se à necropsia, e estudo histopatológico dos rins. Os sinais clínicos apresentados foram apatia, anorexia, poliúria, oligúria, anúria, polidipsia, vômito e diarréia. Pela urinálise observou-se a ocorrência de proteinúria, glicosúria, hematúria, cilindrúria, celulúria e isostenúria; os valores de gama glutamil transpeptidase urinária elevaram-se de forma crescente a partir de 24 horas de administração da gentamicina até o final do experimento, a azotemia foi observada no 12° e 14° dias da pesquisa. Na avaliação histopatológica observou-se nefrose tubular aguda. Com base nos resultados obtidos pode-se concluir que a mensuração da atividade da gama glutamil transpeptidase urinária é um sensível indicador de lesão tubular renal possibilitando o diagnóstico precoce, juntamente com a urinálise.Eleven healthy dogs, ranging from one to five years old, were used for this study. Base line values were determined through five daily samples of urine for urinalysis and urinary gamma glutamyl transpeptidase activity, and blood for serum dosage of BUN and creatinine. Nephrotoxicity was induced using 10mg/kg of gentamicin, 3 times a day (tid, for 14 days. Urine samples were drawn every 24 hours and blood samples every 48 hours, for 14 days. After this period, the dogs were euthanized and necropsy was done for further

  9. Influence of serum levels of alkaline phosphatase and gamma-glutamyl transpeptidase on the prognosis of patients with primary liver cancer undergoing radiofrequency ablation

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    ZHU Ge

    2016-12-01

    Full Text Available ObjectiveTo investigate the influence of serum levels of alkaline phosphatase (ALP and gamma-glutamyltransferase (GGT before treatment on the prognosis of patients with primary liver cancer undergoing radiofrequency ablation. MethodsA total of 165 patients with pathologically or clinically confirmed primary liver cancer who were admitted to Cancer Center of The First Hospital of Jilin University from October 2010 to June 2015 and treated with radiofrequency ablation were enrolled, and their preoperative clinical data were collected. The chi-square test was used for comparison of categorical data between groups, and the Kaplan-Meier method and Cox regression analysis were used to analyze the association of serum ALP and GGT levels before treatment with overall survival, progression-free survival, and clinical features. ResultsThere were significant differences in the 1-, 2-, and 5-year survival rates between the patients with normal (≤135 U/L or abnormal (>135 U/L serum ALP before treatment (91%/90%/35% vs 79%/68%/18%, P=0.01. There were also significant differences in the 1-, 2-, and 5-year survival rates between the patients with normal (≤45 U/L or abnormal (>45 U/L serum GGT before treatment (95%/85%/37% vs 87%/71%/21%, P<0.001. The serum levels of ALP (HR=1.766, 95%CI:1.068-2.921,P=0.027 and GGT (HR=2.312, 95%CI:1.367-3.912,P=0.002 before treatment were closely associated with the overall survival of patients with primary liver cancer after radiofrequency ablation and were independent prognostic factors. There were significant differences in the 1-, 2-, and 5-year progression-free survival rates between the patients with normal (≤135 U/L or abnormal (>135 U/L serum ALP before treatment (72%/52%/14% vs 50%/21%/3%, P<0.001; there were also significant differences in the 1-, 2-, and 5-year progression-free survival rates between the patients with normal (≤45 U/L or abnormal (>45 U/L serum GGT before treatment (81%/62%/18% vs

  10. 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.

    Science.gov (United States)

    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.

  11. Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Pt. 2. Structure-activity relationships with inhibition of hepatic phosphoenolpyruvate carboxykinase, pyruvate carboxylase, and [gamma]-glutamyl transpeptidase activities

    Energy Technology Data Exchange (ETDEWEB)

    Weber, L.W.D.; Stahl, B.U.; Rozman, K. (Kansas Univ. Medical Center, Dept. of Pharmacology, Toxicology and Therapeutics, Kansas City, KS (United States) GSF, Inst. fuer Toxikologie, Neuherberg (Germany)); Lebofsky, M. (Kansas Univ. Medical Center, Dept. of Pharmacology, Toxicology and Therapeutics, Kansas City, KS (United States)); Kettrup, A. (GSF, Inst. fuer Oekologische Chemie, Neuherberg (Germany))

    1992-08-01

    Male Sprague-Dawley rats were treated with an LD[sub 20], LD[sub 50] and LD[sub 80] respectively, of tetra-, penta-, hexa-, hepta-CDD and a mixture of the four CDDs, all carrying chlorine substituents in the biologically crucial 2,3,7, and 8 positions. Specific activities of two key enzymes of gluconeogenesis, viz, phosphoenolpyruvate carboxylkinase (PEPCK) and pyruvate carboxylase (PC), as well as the activity of the preneoplastic marker enzyme [gamma]-glutamyl transpeptidase ([gamma]-GT), were determined in livers of CDD-treated and ad libitum-fed control animals. PEPCK activity showed evidence for dose-related inhibition on the second day after dosing; PC activity was slightly reduced, whereas [gamma]-GT activity was dose-dependently inhibited. By 8 days after dosing PEPCK activities were dose-dependently decreased after administration of all four CDDs and their mixture. PC activities were significantly reduced, but no dose-response was evident. The activity of [gamma]-GT was dose-dependently inhibited, but only to a value of 25% below control activities. It is concluded that CDDs share a common mechanism of acute toxicity, viz, inhibition of glucocorticoid-dependent enzymes which results in a derailment of intermediary metabolism not compatible with survival of the animals. (orig.).

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

    Energy Technology Data Exchange (ETDEWEB)

    Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Deschamps, Frederic [Institut Gustave Roussy, Department of Interventional Radiology (France); Boulin, Mathieu [University Hospital, INSERM U866 (France); Boige, Valerie; Malka, David; Ducreux, Michel [Institut Gustave Roussy, Department of Digestive Oncology (France); Hillon, Patrick [University Hospital, INSERM U866 (France); Baere, Thierry de [Institut Gustave Roussy, Department of Interventional Radiology (France)

    2012-10-15

    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, 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.

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

    International Nuclear Information System (INIS)

    Guiu, Boris; Deschamps, Frédéric; Boulin, Mathieu; Boige, Valérie; Malka, David; Ducreux, Michel; Hillon, Patrick; Baère, Thierry de

    2012-01-01

    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, 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.

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

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    Claudia Torino

    2016-01-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    Bridges, R.J.; Meister, A.

    1985-01-01

    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 35 S after incubation of the slices in media containing gamma-glutamyl methionine [ 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 was 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

  16. Loci Affecting Gamma-Glutamyl Transferase in Adults and Adolescents Show Age X SNP interaction and Cardiometabolic Disease Associations

    NARCIS (Netherlands)

    Middelberg, R.P.S.; Benyamin, B.; de Moor, M.H.M.; Warrington, N.M.; Gordon, S.; Henders, A.K.; Medland, S.E.; Nyholt, DR; de Geus, E.J.C.; Hottenga, J.J.; Willemsen, G.; Beilin, L.J.; Mori, T.A.; Wright, M.J.; Heath, A.C.; Madden, P.A.F.; Boomsma, D.I.; Pennell, C.E.; Montgomery, G.W.; Martin, N.G.; Whitfield, J.B.

    2012-01-01

    Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in

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

    Science.gov (United States)

    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

  18. Ablation of Mrds1/Ofcc1 induces hyper-γ-glutamyl transpeptidasemia without abnormal head development and schizophrenia-relevant behaviors in mice.

    Directory of Open Access Journals (Sweden)

    Tetsuo Ohnishi

    Full Text Available 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.

  19. Serum γ-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption

    Directory of Open Access Journals (Sweden)

    Han Seok Choi

    2016-03-01

    Full Text Available Backgroundγ-Glutamyl transferase (GGT is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD in Korean adults.MethodsA total of 462 subjects (289 men and 173 women, who visited Severance Hospital for medical checkup, were included in this study. BMD was measured using dual energy X-ray absorptiometry. Cross-sectional association between serum GGT and BMD was evaluated.ResultsAs serum GGT levels increased from the lowest tertile (tertile 1 to the highest tertile (tertile 3, BMD decreased after adjusting for confounders such as age, body mass index, amount of alcohol consumed, smoking, regular exercise, postmenopausal state (in women, hypertension, diabetes mellitus, and hypercholesterolemia. A multiple linear regression analysis showed a negative association between log-transformed serum GGT levels and BMD. In a multiple logistic regression analysis, tertile 3 of serum GGT level was associated with an increased risk for low bone mass compared to tertile 1 (odds ratio, 2.271; 95% confidence interval, 1.340 to 3.850; P=0.002.ConclusionSerum GGT level was inversely associated with BMD in Korean adults. Further study is necessary to fully elucidate the mechanism of the inverse relationship.

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

    Science.gov (United States)

    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, pcopper 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, pcopper 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.

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

    Science.gov (United States)

    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

  2. SERUM GAMMA-GLUTAMYL TRANSFERASE AS A BIOMARKER OF TYPE-2 DM AMONG CIGARETTE SMOKERS

    Directory of Open Access Journals (Sweden)

    K. Suganthy

    2017-03-01

    Full Text Available BACKGROUND Smoking is one of the most common addictions of modern times and needs to be studied in a community as a public health issue. Also, smoking is a modifiable risk factor for type-2 DM. The smoking-related diseases share common pathophysiologies of imbalance of systemic oxidants and antioxidant status, increased inflammatory reactions, insulin resistance and dyslipidaemia. Biochemical assay of serum Gamma-Glutamyl Transferase (GGT activity is a low cost and highly sensitive laboratory test. Studies have indicated GGT is moderately elevated before the onset of other traditional risk factors for type-2 DM. So, among hepatic markers, the baseline GGT analysis can be an early risk marker of type 2 diabetes in cigarette smokers has to be studied. MATERIALS AND METHODS This is a case-control study on male cigarette smokers. 57 smokers were studied clinically and biochemically for plasma insulin, glucose and liver enzymes including GGT using standard biochemical methods and compared with 42 age and sex matched non-smokers as controls. RESULTS The mean serum GGT in smokers (25.45 ± 10.8 was increased compared to non-smokers (18.8 ± 5.8. Smokers GGT (r=0.396 and HOMA-IR (r=0.352 showed significant positive association with duration of smoking (p24 IU/L. Regression analysis showed none of the diabetic risk factors were observed to be dependent on GGT including other liver enzymes. Regression analysis showed GGT is not an independent risk factor for DM. Although, the mean fasting blood glucose (91.4 ± 21.3, BMI (26.1 ± 9.3 and HOMA-IR (7.3 ± 2.3 was increased among cigarette smokers with GGT >24 IU/L. CONCLUSION The baseline GGT assay in cigarette smokers might be associated with the proinflammatory status or be a marker of oxidative stress of smoke toxins. Smokers with baseline GGT >24 IU/L develop insulin resistance should be investigated in future longitudinal studies for prediabetes to consider cigarette smoking as an important modifiable

  3. The influence of interleukin-1beta on gamma-glutamyl transpeptidase activity in rat hippocampus

    Czech Academy of Sciences Publication Activity Database

    Kaiser, M.; Mareš, Vladislav; Šťastný, František; Bubeníková-Valešová, V.; Lisá, Věra; Suchomel, P.; Balcar, V. J.

    2006-01-01

    Roč. 55, č. 4 (2006), s. 461-465 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NF7626 Institutional research plan: CEZ:AV0Z50110509 Keywords : interleukin-1beta * gamma- glutamyltranspeptidase * hippocampus Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  4. γ-Glutamyl Transferase as a Risk Factor for All-Cause or Cardiovascular Disease Mortality Among 5912 Ischemic Stroke.

    Science.gov (United States)

    Tu, Wen-Jun; Liu, Qiang; Cao, Jian-Lei; Zhao, Sheng-Jie; Zeng, Xian-Wei; Deng, Ai-Jun

    2017-10-01

    The aim of the study was to evaluate the association of the measurement of serum γ-glutamyl transferase (GGT) concentrations at admission with 1-year all-cause or cardiovascular disease (CVD) mortality in patients with acute ischemic stroke. This prospective, multicenter cohort study was conducted in 4 stroke centers in China. Baseline GGT measurements were tested. The relationship of GGT to the risk of death from all-cause or CVD was examined among 1-year follow-up patients. We recorded results from 5912 patients with stroke. In those patients, 51.0% were men, and the median age was 61 years. In both men and women, high GGT was significantly associated with total mortality from all-cause or CVD ( P mortality from all-cause and CVD, respectively. With an area under the curve of 0.69 (95% confidence interval, 0.66-0.73), GGT showed a significantly greater discriminatory ability to predict all-cause mortality as compared with others factors. GGT improved the National Institutes of Health Stroke Scale score (area under the curve of the combined model, 0.75 [95% confidence interval, 0.73-0.78]; P mortality in patients with ischemic stroke. © 2017 American Heart Association, Inc.

  5. gamma-Glutamyl dipeptides in Petiveria alliacea.

    Science.gov (United States)

    Kubec, Roman; Musah, Rabi A

    2005-10-01

    Three gamma-glutamyl dipeptides have been isolated from Petiveria alliacea L. roots. These dipeptides include (S(C2)R(C7))-gamma-glutamyl-S-benzylcysteine together with two diastereomeric sulfoxides, namely (S(C2)R(C7)R(S))- and (S(C2)R(C7)R(S))-gamma-glutamyl-S-benzylcysteine S-oxides (gamma-glutamyl-petiveriins A and B, respectively). Their structures and absolute configurations have been determined by NMR, MALDI-HRMS, IR and CD spectroscopy, and confirmed by comparison with authentic compounds obtained by synthesis.

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

    Science.gov (United States)

    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 PCOS women who were normoweight and overweight than the normoweight and overweight women in the control group (p 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.

  7. GGT2.0: Versatile Software for visualization and analysis of genetic data

    NARCIS (Netherlands)

    Berloo, van R.

    2008-01-01

    Ever since its first release in 1999, the free software package for visualization of molecular marker data, graphical genotype (GGT), has been constantly adapted and improved. The GGT package was developed in a plant-breeding context and thus focuses on plant genetic data but was not intended to be

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

    Science.gov (United States)

    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.

  9. 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.

    Science.gov (United States)

    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 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.

  10. Alanine aminotransferase, gamma-glutamyltransferase (GGT) and all-cause mortality: results from a population-based Danish twins study alanine aminotransferase, GGT and mortality in elderly twins

    DEFF Research Database (Denmark)

    Fraser, Abigail; Thinggaard, Mikael; Christensen, Kaare

    2009-01-01

    Abstract Background/Aims: Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are widely used markers of liver disease. Several population-based cohort studies have found associations of these liver enzymes with all-cause mortality. None of these studies controlled for genetic...... for potential confounders and existing diabetes and cardiovascular disease. Environmental developmental origins may explain the association, but larger twin studies are required to replicate our findings....

  11. High-sensitivity c-reactive protein and gamma-glutamyl transferase levels are synergistically associated with metabolic syndrome in community-dwelling persons

    Directory of Open Access Journals (Sweden)

    Takayama Shuzo

    2010-12-01

    Full Text Available Abstract Background Metabolic syndrome (MetS is associated with an increased risk of major cardiovascular events. Increased high-sensitivity C-reactive protein (hsCRP levels are associated with MetS and its components. Changes in gamma-glutamyl transferase (GGT levels in response to oxidative stress are also associated with MetS, and the levels could be modulated by hsCRP. Methods From a single community, we recruited 822 men (mean age, 61 ± 14 years and 1,097 women (63 ± 12 years during their annual health examination. We investigated whether increased hsCRP and GGT levels are synergistically associated with MetS and insulin resistance evaluated by Homeostasis of model assessment of insulin resistance (HOMA-IR. Results Of these subjects, 141 men (17.2% and 170 women (15.5% had MetS. Participants with MetS had a higher hsCRP and GGT level than those without MetS in both genders, and the HOMA-IR increased significantly in correlation with an increase in hsCRP and GGT. In men, the adjusted odds ratios (95% confidence interval for MetS across tertiles of hsCRP and GGT were 1.00, 1.69 (1.01-2.80, and 2.13 (1.29-3.52, and 1.00, 3.26 (1.84-5.78 and 6.11 (3.30-11.3, respectively. In women, the respective corresponding values were 1.00, 1.54 (0.92-2.60, and 3.08 (1.88-5.06, and 1.00, 1.70 (1.04-2.79 and 2.67 (1.66-4.30. The interaction between increased hsCRP and GGT was a significant and independent determinant for MetS and insulin resistance in both genders. Conclusions These results suggested that higher CRP and GGT levels were synergistically associated with MetS and insulin resistance, independently of other confounding factor in the general population.

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

    Science.gov (United States)

    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. Trino IB ameliorates the oxidative stress of cryptorchidism in the rat ...

    African Journals Online (AJOL)

    The study examined the effect of Trino IB, a mixture of oleuropein and -lipoic acid, on the plasma concentration of g-glutamyl transpeptidase (GGT), malondialdehyde (MDA), sperm count and apoptotic degeneration of testicular germ cells in experimentally induced cryptorchidism in adult male rats. Oral administration of ...

  14. Peptidoglycan transpeptidase inhibition in Pseudomonas aeruginosa and Escherichia coli by Penicillins and Cephalosporins.

    Science.gov (United States)

    Moore, B A; Jevons, S; Brammer, K W

    1979-04-01

    Peptidoglycan transpeptidase activity has been studied in cells of Escherichia coli 146 and Pseudomonas aeruginosa 56 made permeable to exogenous, nucleotide-sugar peptidoglycan precursors by ether treatment. Transpeptidase activity was inhibited, in both organisms, by a range of penicillins and cephalosporins, the Pseudomonas enzyme being more sensitive to inhibition in each case. Conversely, growth of E. coli 146 was more susceptible to these antibiotics than growth of P. aeruginosa 56. Furthermore, similar transpeptidase inhibition values were ob-obtained for the four penicillins examined against the Pseudomonas enzyme, although only two of these (carbenicillin and pirbenicillin) inhibited the growth of this organism. We therefore conclude that the high resistance of P. aeruginosa 56 to growth inhibition by most beta-lactam antibiotics cannot be due to an insensitive peptidoglycan transpeptidase.

  15. Is gamma glutamyl transferase a diagnostic marker of prostate ...

    African Journals Online (AJOL)

    McRoy

    2013-08-05

    Aug 5, 2013 ... Research Unit, Institute for Advance Medical Research and Training, College of Medicine,. University of .... oxidative stress in BPH and prostate cancer and this suggests that .... American journal of Clinical Nutrition: GGT levels vary ... reproduction in any medium, provided the original work is properly cited.

  16. Reconstructive Effects of Percutaneous Electrical Stimulation Combined with GGT Composite on Large Bone Defect in Rats

    Directory of Open Access Journals (Sweden)

    Bo-Yin Yang

    2013-01-01

    Full Text Available Previous studies have shown the electromagnetic stimulation improves bone remodeling and bone healing. However, the effect of percutaneous electrical stimulation (ES was not directly explored. The purpose of this study was to evaluate effect of ES on improvement of bone repair. Twenty-four adult male Sprague-Dawley rats were used for cranial implantation. We used a composite comprising genipin cross-linked gelatin mixed with tricalcium phosphate (GGT. Bone defects of all rats were filled with the GGT composites, and the rats were assigned into six groups after operation. The first three groups underwent 4, 8, and 12 weeks of ES, and the anode was connected to the backward of the defect on the neck; the cathode was connected to the front of the defect on the head. Rats were under inhalation anesthesia during the stimulation. The other three groups only received inhalation anesthesia without ES, as control groups. All the rats were examined afterward at 4, 8, and 12 weeks. Radiographic examinations including X-ray and micro-CT showed the progressive bone regeneration in the both ES and non-ES groups. The amount of the newly formed bone increased with the time between implantation and examination in the ES and non-ES groups and was higher in the ES groups. Besides, the new bone growth trended on bilateral sides in ES groups and accumulated in U-shape in non-ES groups. The results indicated that ES could improve bone repair, and the effect is higher around the cathode.

  17. Inactivation of Mycobacterium tuberculosis l,d-Transpeptidase LdtMt1 by Carbapenems and Cephalosporins

    Science.gov (United States)

    Dubée, Vincent; Triboulet, Sébastien; Mainardi, Jean-Luc; Ethève-Quelquejeu, Mélanie; Gutmann, Laurent; Marie, Arul; Dubost, Lionel

    2012-01-01

    The structure of Mycobacterium tuberculosis peptidoglycan is atypical since it contains a majority of 3→3 cross-links synthesized by l,d-transpeptidases that replace 4→3 cross-links formed by the d,d-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate these l,d-transpeptidases, and meropenem combined with clavulanic acid is bactericidal against extensively drug-resistant M. tuberculosis. Here, we used mass spectrometry and stopped-flow fluorimetry to investigate the kinetics and mechanisms of inactivation of the prototypic M. tuberculosis l,d-transpeptidase LdtMt1 by carbapenems (meropenem, doripenem, imipenem, and ertapenem) and cephalosporins (cefotaxime, cephalothin, and ceftriaxone). Inactivation proceeded through noncovalent drug binding and acylation of the catalytic Cys of LdtMt1, which was eventually followed by hydrolysis of the resulting acylenzyme. Meropenem rapidly inhibited LdtMt1, with a binding rate constant of 0.08 μM−1 min−1. The enzyme was unable to recover from this initial binding step since the dissociation rate constant of the noncovalent complex was low (carbapenem side chains affected both the binding and acylation steps, ertapenem being the most efficient LdtMt1 inactivator. Cephalosporins also formed covalent adducts with LdtMt1, although the acylation reaction was 7- to 1,000-fold slower and led to elimination of one of the drug side chains. Comparison of kinetic constants for drug binding, acylation, and acylenzyme hydrolysis indicates that carbapenems and cephems can both be tailored to optimize peptidoglycan synthesis inhibition in M. tuberculosis. PMID:22615283

  18. Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.

    Directory of Open Access Journals (Sweden)

    Salvatore Petta

    Full Text Available BACKGROUND AND AIMS: Serum levels of γ-glutamyl-transpeptidase(γ-GT were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD, genotype 1 chronic hepatitis C (G1CHC and chronic hepatitis B (CHB, we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR and severity of liver fibrosis. METHODS: 843 consecutive patients with chronic liver disease (CLD(193 NAFLD, 481 G1CHC, 169 CHB were evaluated by liver biopsy (Kleiner and Scheuer scores and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT. RESULTS: By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120-6.564,p = 0.02, G1CHC (OR3.461,CI2.138-5.603,p80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079-15.970,p = 0.03 for NAFLD; OR2.250,CI1.211-4.181,p = 0.01 for G1CHC; OR3.096,CI2.050-34.220,p = 0.01 for CHB. CONCLUSIONS: In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

  2. Synthesis of Taste-Active γ-Glutamyl Dipeptides during Sourdough Fermentation by Lactobacillus reuteri.

    Science.gov (United States)

    Zhao, Cindy J; Gänzle, Michael G

    2016-10-12

    This study aimed to assess whether peptides influence the taste of sourdough bread. γ-Glutamyl dipeptides with known kokumi taste threshold, namely γ-Glu-Glu, γ-Glu-Leu, γ-Glu-Ile, γ-Glu-Phe, γ-Glu-Met, and γ-Glu-Val, were identified in sourdough by liquid chromatography-tandem mass spectrometry in MRM mode. γ-Glutamyl dipeptides were found in higher concentrations in sourdough fermented with Lactobacillus reuteri when compared to the chemically acidified controls. Proteolysis was an important factor for generation of γ-glutamyl dipeptides. Sourdoughs fermented with four strains of L. reuteri had different concentrations of γ-Glu-Glu, γ-Glu-Leu, and γ-Glu-Met, indicating strain-specific differences in enzyme activity. Buffer fermentations with L. reuteri confirmed the ability of the strains to convert amino acids to γ-glutamyl dipeptides as well as the strain-specific differences. Sensory evaluation of bread revealed that sourdough bread with higher concentrations of γ-glutamyl dipeptides ranked higher with respect to the taste intensity when compared to regular bread and type I sourdough bread. Sourdough breads fermented with L. reuteri LTH5448 and L. reuteri 100-23 differed with respect to the intensity of the salty taste; this difference corresponded to a different concentration of γ-glutamyl dipeptides. These results suggest a strain-specific contribution of γ-glutamyl dipeptides to the taste of bread. The use of sourdough fermented with glutamate and kokumi peptide accumulating lactobacilli improved the taste of bread without adverse effect on other taste or quality attributes.

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

    Energy Technology Data Exchange (ETDEWEB)

    Suryadinata, Randy, E-mail: randy.suryadinata@csiro.au; Seabrook, Shane A.; Adams, Timothy E.; Nuttall, Stewart D.; Peat, Thomas S., E-mail: randy.suryadinata@csiro.au [Commonwealth Scientific and Industrial Research Organisation, 343 Royal Parade, Parkville, Victoria 3052 (Australia)

    2015-06-30

    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 of 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.

  4. Targeting of human GGT in a renal cell carcinoma mouse model with 99mTc-HYNIC-mAb 138H11

    International Nuclear Information System (INIS)

    Kuenstler, J.U.; Seifert, S.; Zimmermann, J.; Fischer, P.; Invancevic, V.; Johannsen, B.

    2002-01-01

    The study shows that the specific tumor uptake of 99m Tc-HYNIC-mAb 138H11 in GGT positive tumours was 2 to 5 times as high as in the controls. A high unspecific background activity was observed in the blood and in all organs well supplied with blood. (orig.)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    Yamada, Mototsugu; Watanabe, Takashi; Baba, Nobuyoshi; Miyara, Takako; Saito, Jun; Takeuchi, Yasuo

    2008-01-01

    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 3 2 1 2, with unit-cell parameters a = b = 86.39, 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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Mototsugu, E-mail: mototsugu-yamada@meiji.co.jp; Watanabe, Takashi; Baba, Nobuyoshi; Miyara, Takako; Saito, Jun; Takeuchi, Yasuo [Pharmaceutical Research Center, Meiji Seika Kaisha Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567 (Japan)

    2008-04-01

    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, 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.

  10. DETERMINAÇÃO DOS VALORES MÉDIOS DAS ENZIMAS AST, DHL, gGT E FAS NO SORO DE EQUINOS SADIOS EM SANTA MARIA, RS

    Directory of Open Access Journals (Sweden)

    Sônia Terezinha dos Anjos Lopes

    1993-12-01

    Full Text Available Foram usados 50 eqüinos sadios provenientes do Batalhão de Polícia Montada da Brigada Militar em Santa Maria, RS, sendo 43 machos e 7 fêmeas com idade variadas a partir de 3 anos. Foram colhidos 10ml de sangue da jugular para determinação dos valores da atividade sérica das enzimas aspartato-aminotransferase (AST, desidrogenase lática (DHL, gama-glutamiltransferase (gGT e fosfatase alcalina sérica (FAS. Os resultados encontrados para AST foi de 101 - 190U/I com média de 130UI; DHL foi de 100 - 421 U/l com média de 182U/I; gGT foi de 2 - 27U/I com média de 6.5U/I e FAS foi de 103 - 335U/I com média de 190U/I. A partir de outubro/1992 estes valores passaram a ser referência no laboratório de Patologia Clínica do Hospital de Clinicas Veterinárias da Universidade Federal de Santa Maria.

  11. 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.

    Science.gov (United States)

    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.

  12. Redox status affects the catalytic activity of glutamyl-tRNA synthetase

    DEFF Research Database (Denmark)

    Katz, Assaf; Banerjee, Rajat; de Armas, Merly

    2010-01-01

    Glutamyl-tRNA synthetases (GluRS) provide Glu-tRNA for different processes including protein synthesis, glutamine transamidation and tetrapyrrole biosynthesis. Many organisms contain multiple GluRSs, but whether these duplications solely broaden tRNA specificity or also play additional roles in t...... inactivation by hemin plus hydrogen peroxide. The sensitivity to oxidation of A. ferrooxidans GluRS1 might provide a means to regulate tetrapyrrole and protein biosynthesis in response to extreme changes in both the redox and heme status of the cell via a single enzyme....

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

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2016-06-01

    Full Text Available 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.

  14. Causal Mediation Analysis with Multiple Mediators

    OpenAIRE

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

    2014-01-01

    : 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...

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

    Science.gov (United States)

    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.

  16. γ-Glutamyl-dipeptides: Easy tools to rapidly probe the stereoelectronic properties of ionotropic glutamate receptor binding pocket

    DEFF Research Database (Denmark)

    Tamborini, Lucia; Nicosia, Veronica; Conti, Paola

    2016-01-01

    γ-Glutamyl-dipeptides, built by condensing the distal carboxylate of L-Glu (or D-Glu) onto a series of differently functionalized amino acids, were prepared and used as tools for rapidly probing the stereoelectronic properties of iGluRs, searching for subtype-selective ligands.......γ-Glutamyl-dipeptides, built by condensing the distal carboxylate of L-Glu (or D-Glu) onto a series of differently functionalized amino acids, were prepared and used as tools for rapidly probing the stereoelectronic properties of iGluRs, searching for subtype-selective ligands....

  17. Glutathione provides a source of cysteine essential for intracellular multiplication of Francisella tularensis.

    Directory of Open Access Journals (Sweden)

    Khaled Alkhuder

    2009-01-01

    Full Text Available Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. Its ability to multiply and survive in macrophages is critical for its virulence. By screening a bank of HimarFT transposon mutants of the F. tularensis live vaccine strain (LVS to isolate intracellular growth-deficient mutants, we selected one mutant in a gene encoding a putative gamma-glutamyl transpeptidase (GGT. This gene (FTL_0766 was hence designated ggt. The mutant strain showed impaired intracellular multiplication and was strongly attenuated for virulence in mice. Here we present evidence that the GGT activity of F. tularensis allows utilization of glutathione (GSH, gamma-glutamyl-cysteinyl-glycine and gamma-glutamyl-cysteine dipeptide as cysteine sources to ensure intracellular growth. This is the first demonstration of the essential role of a nutrient acquisition system in the intracellular multiplication of F. tularensis. GSH is the most abundant source of cysteine in the host cytosol. Thus, the capacity this intracellular bacterial pathogen has evolved to utilize the available GSH, as a source of cysteine in the host cytosol, constitutes a paradigm of bacteria-host adaptation.

  18. Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine-paclitaxel nanoconjugate

    Directory of Open Access Journals (Sweden)

    Sang Van

    2010-10-01

    Full Text Available Sang Van1, Sanjib K Das1, Xinghe Wang1, Zhongling Feng1, Yi Jin1, Zheng Hou1, Fu Chen1, Annie Pham1, Nan Jiang1, Stephen B Howell2, Lei Yu11Nitto Denko Technical Corporation, Oceanside, CA, USA; 2Moores Cancer Center, University of California, La Jolla, San Diego, CA, USAAbstract: The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine-paclitaxel nanoconjugate (PGG-PTX that would improve the therapeutic index of paclitaxel (PTX. PGG-PTX is a modification of poly(L-glutamic acid-paclitaxel conjugate (PGA-PTX in which an additional glutamic acid has been added to each glutamic side chain in the polymer. PGG-PTX has higher water-solubility and faster dissolution than PGA-PTX. Unlike PGA-PTX, PGG-PTX self-assembles into nanoparticles, whose size remains in the range of 12–15 nm over the concentration range from 25 to 2,000 µg/mL in saline. Its critical micellar concentration in saline was found to be ~25 µg/mL. The potency of PGG-PTX when tested in vitro against the human lung cancer H460 cell line was comparable to other known polymer-PTX conjugates. However, PGG-PTX possesses lower toxicity compared with PGA-PTX in mice. The maximum tolerated dose of PGG-PTX was found to be 350 mg PTX/kg, which is 2.2-fold higher than the maximum tolerated dose of 160 mg PTX/kg reported for the PGA-PTX. This result indicates that PGG-PTX was substantially less toxic in vivo than PGA-PTX.Keywords: nanoconjugates, poly(L-glutamic acid, poly(L-γ-glutamyl-glutamine-paclitaxel, nanoparticles, anticancer

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  1. A Novel Glutamyl (Aspartyl)-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application.

    Science.gov (United States)

    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.

  2. A Novel Glutamyl (Aspartyl-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application.

    Directory of Open Access Journals (Sweden)

    Timo Stressler

    Full Text Available 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.

  3. Multiple γ-glutamylation: A novel type of post-translational modification in a diapausing Artemia cyst protein

    International Nuclear Information System (INIS)

    Hasegawa, Mai; Ikeda, Yuka; Kanzawa, Hideaki; Sakamoto, Mika; Goto, Mina; Tsunasawa, Susumu; Uchiumi, Toshio; Odani, Shoji

    2010-01-01

    A highly hydrophilic, glutamate-rich protein was identified in the aqueous phenol extract from the cytosolic fraction of brine shrimp (Artemia franciscana) diapausing cysts and termed Artemia phenol soluble protein (PSP). Mass spectrometric analysis revealed the presence of many protein peaks around m/z 11,000, separated by 129 atomic mass units; this value corresponds to that of glutamate, which is strongly suggestive of heterogeneous polyglutamylation. Polyglutamylation has long been known as the functionally important post-translational modification of tubulins, which carry poly(L-glutamic acid) chains of heterogeneous length branching off from the main chain at the γ-carboxy groups of a few specific glutamate residues. In Artemia PSP, however, Edman degradation of enzymatic peptides revealed that at least 13, and presumably 16, glutamate residues were modified by the attachment of a single L-glutamate, representing a hitherto undescribed type of post-translational modification: namely, multiple γ-glutamylation or the addition of a large number of glutamate residues along the polypeptide chain. Although biological significance of PSP and its modification is yet to be established, suppression of in vitro thermal aggregation of lactate dehydrogenase by glutamylated PSP was observed.

  4. Mitochondrial and cytoplasmic isoleucyl-, glutamyl- and arginyl-tRNA synthetases of yeast are encoded by separate genes.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  6. Structure and Inhibitor Specificity of L,D-Transpeptidase (LdtMt2) from Mycobacterium tuberculosis and Antibiotic Resistance: Calcium Binding Promotes Dimer Formation.

    Science.gov (United States)

    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.

  7. Dietary Antioxidants Effectiveness on Carbon Tetrachloride-Induced Hepatotoxicity in Adult Female Albino Rats

    International Nuclear Information System (INIS)

    EI-Sherbiny, E.M.; EI-Mahdy, A.A.

    2008-01-01

    Hepatic toxicity through carbon tetrachloride (CCI 4 ) induced lipid peroxidation was extensively used in experimental models to understand the cellular mechanisms behind oxidative damage and to evaluate the therapeutic potential of drugs and dietary antioxidants. The ameliorative effect of Aloe vera juice and carrot supplementation on hepato carcinogenesis induced by carbon tetrachloride in adult female albino rats was investigated. The carcinogenic process was determined by measuring gamma-glutamyl transpeptidase (GGT), ornithine carbamyl transferase (OCT), thiobarbituric acid reactive substances (TBARs), representing levels of lipid peroxides, and carcinoembryonic antigen (CEA) in the sera of female albino rats. Carbon tetrachloride significantly elevated the serum GGT, OCT activities and the level of TBARs. Administration of Aloe vera leaf juice filtrate after CCl 4 treatment resulted in a non-significant modification in GGT, OCT activities and significantly improved the level of TBARs in comparison with control. Supplementation of carrot to CCI 4 treated animals led to a great amelioration in OCT activity and TBARs level, whereas GGT activity was ameliorated but statistically changed compared to control. There was a non-significant alteration in the level of CEA in all treated groups compared to normal control one

  8. Hepatopancreaticobiliary Values after Thoracoabdominal Aneurysm Repair

    Science.gov (United States)

    Wu, Darrell; Coselli, Joseph S.; Johnson, Michael L.; LeMaire, Scott A.

    2014-01-01

    Background: After thoracoabdominal aortic aneurysm (TAAA) repair, blood tests assessing hepatopancreaticobiliary (HPB) organs commonly have abnormal results. The clinical significance of such abnormalities is difficult to determine because the expected postoperative levels have not been characterized. Therefore, we sought to establish expected trends in HPB laboratory values after TAAA repair. Methods: This 5-year study comprised 155 patients undergoing elective Crawford extent II TAAA repair. In accordance with a prospective study protocol, all repairs involved left-sided heart bypass, selective visceral perfusion, and cold renal perfusion. Blood levels of aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), total bilirubin, amylase, and lipase were measured before TAAA repair and for 7 days afterward. Ratios between postoperative and baseline levels were compared for each time point with 95% confidence intervals. Results: Temporal patterns for the laboratory values varied greatly. Amylase, lipase, and AST underwent significant early increases before decreasing to preoperative levels. LDH increased immediately and remained significantly elevated, whereas ALT increased more gradually. GGT remained near baseline through postoperative day 4, and then increased to more than twice baseline. Total bilirubin never differed significantly from baseline. After adjusted analysis, the ischemic time predicted the maximum AST, lipase, GGT, and LDH values. Conclusions: Although most HPB laboratory values increase significantly after elective TAAA repair, the temporal trends for different values vary substantially. The ischemic time predicts the maximum AST, lipase, GGT, and LDH levels. These trends should be considered when laboratory values are assessed after TAAA repair. PMID:26798731

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

    Science.gov (United States)

    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

  10. Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity.

    Science.gov (United States)

    Xia, Pengyan; Ye, Buqing; Wang, Shuo; Zhu, Xiaoxiao; Du, Ying; Xiong, Zhen; Tian, Yong; Fan, Zusen

    2016-04-01

    Cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA during viral infection and catalyzes synthesis of the dinucleotide cGAMP, which activates the adaptor STING to initiate antiviral responses. Here we found that deficiency in the carboxypeptidase CCP5 or CCP6 led to susceptibility to DNA viruses. CCP5 and CCP6 were required for activation of the transcription factor IRF3 and interferons. Polyglutamylation of cGAS by the enzyme TTLL6 impeded its DNA-binding ability, whereas TTLL4-mediated monoglutamylation of cGAS blocked its synthase activity. Conversely, CCP6 removed the polyglutamylation of cGAS, whereas CCP5 hydrolyzed the monoglutamylation of cGAS, which together led to the activation of cGAS. Therefore, glutamylation and deglutamylation of cGAS tightly modulate immune responses to infection with DNA viruses.

  11. Role of γ-glutamyl transferase levels in prediction of high cardiovascular risk among patients with non-alcoholic fatty liver disease

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    Benan Kasapoglu

    2016-01-01

    Full Text Available Background & objectives: Non-alcoholic fatty liver disease (NAFLD is an important cause of elevated liver functions. There is evidence showing an association between NAFLD and subclinical atherosclerosis independent of traditional risk factors. We undertook this retrospective study to determine the association of Framingham cardiovascular risk scoring system with liver function tests and inflammatory markers and to find the role of liver function tests in determination of CVD risk among non-obese and non-diabetic subjects with non-alcoholic fatty liver disease. Methods: A total of 2058 patients were included in the study. Framingham cardiovascular risk scoring was done of all patients according to the age, gender, systolic blood pressure, serum total cholesterol and HDL cholesterol levels, smoking and antihypertensive medication history. Liver function test, lipid profile, insulin, uric acid, ferritin levels, etc. were determined. Results: According to the ultrasonography findings, patients were grouped as without any fatty infiltration of the liver (control group (n=982, mild (n= 473, moderate (n=363 and severe fatty liver disease (n= 240 groups. In severe fatty liver disease group, the mean Framingham cardiovascular risk score was significantly higher than that of other groups. t0 here was a positive correlation between GGT, uric acid and ferritin levels with Framingham cardiovascular score. In multivariate analysis, high GGT levels were positively associated with high-risk disease presence (OR: 3.02, 95% CI: 2.62-3.42 compared to low GGT levels independent of the age and sex. Interpretation & conclusions: Cardiovascular disease risk increases with the presence and stage of fatty liver disease. Our findings showed a positive correlation between elevated GGT levels and Framingham cardiovascular risk scoring system among non-diabetic, non-obese adults which could be important in clinical practice. Though in normal limits, elevated GGT levels

  12. Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting

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    Ozge Korkmaz

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. DESIGN AND SETTING: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. METHODS : 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located, and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9; second group (thrombus in main pulmonary artery branches; n = 71; third group (thrombus in pulmonary artery segmental branches; n = 34; and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8. RESULTS : Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009 and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033 remained independently associated with proximally localized thrombus in pulmonary artery. CONCLUSIONS : The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.

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

    Science.gov (United States)

    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. Transpeptidase activity of penicillin-binding protein SpoVD in peptidoglycan synthesis conditionally depends on the disulfide reductase StoA.

    Science.gov (United States)

    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.

  15. Targeting the cell wall of Mycobacterium tuberculosis: a molecular modeling investigation of the interaction of imipenem and meropenem with L,D-transpeptidase 2.

    Science.gov (United States)

    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.

  16. MHJ_0125 is an M42 glutamyl aminopeptidase that moonlights as a multifunctional adhesin on the surface of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Robinson, Mark W; Buchtmann, Kyle A; Jenkins, Cheryl; Tacchi, Jessica L; Raymond, Benjamin B A; To, Joyce; Roy Chowdhury, Piklu; Woolley, Lauren K; Labbate, Maurizio; Turnbull, Lynne; Whitchurch, Cynthia B; Padula, Matthew P; Djordjevic, Steven P

    2013-04-17

    Bacterial aminopeptidases play important roles in pathogenesis by providing a source of amino acids from exogenous proteins, destroying host immunological effector peptides and executing posttranslational modification of bacterial and host proteins. We show that MHJ_0125 from the swine respiratory pathogen Mycoplasma hyopneumoniae represents a new member of the M42 class of bacterial aminopeptidases. Despite lacking a recognizable signal sequence, MHJ_0125 is detectable on the cell surface by fluorescence microscopy and LC-MS/MS of (i) biotinylated surface proteins captured by avidin chromatography and (ii) peptides released by mild trypsin shaving. Furthermore, surface-associated glutamyl aminopeptidase activity was detected by incubation of live M. hyopneumoniae cells with the diagnostic substrate H-Glu-AMC. MHJ_0125 moonlights as a multifunctional adhesin, binding to both heparin and plasminogen. Native proteomics and comparative modelling studies suggest MHJ_0125 forms a dodecameric, homopolymeric structure and provide insight into the positions of key residues that are predicted to interact with heparin and plasminogen. MHJ_0125 is the first aminopeptidase shown to both bind plasminogen and facilitate its activation by tissue plasminogen activator. Plasmin cleaves host extracellular matrix proteins and activates matrix metalloproteases, generating peptide substrates for MHJ_0125 and a source of amino acids for growth of M. hyopneumoniae. This unique interaction represents a new paradigm in microbial pathogenesis.

  17. Does kombucha tea reduce the damage-induced by radiation exposure?

    International Nuclear Information System (INIS)

    Gharib, O.A.

    2007-01-01

    This work has been performed to investigate the protective effect and the antimicrobial activity that occur following oral administration of kombucha tea (kt) ferment in rats with a fractionated dose of 9 Gy. The protective effect of kt ferment was monitored by assessment of serum enzymes activities of creatin phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) and concentrations of urea and creatinine as well as contents of reduced glutathione (GSH) and malonaldehyde (MDA) in heart, liver and kidney tissues. Besides evaluation of the antimicrobial activity was carried out by determination of the lactic acid bacterial (LAB) count as an example of the beneficial bacteria in the rat intestine and the Staphylococcus aureus bacteria (S. aureus) count as an example of the pathogenic bacteria for rats. The results obtained suggest that administration of this ferment tea could ameliorate biochemical and microbial disturbances in irradiated rats

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

    Science.gov (United States)

    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.

  19. Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic γ-ray-irradiation in the rat liver

    International Nuclear Information System (INIS)

    Ida, Katsuya; Nakamura, Satoshi; Muro, Hiroyuki; Takai, Michikatsu; Kaneko, Masao

    1995-01-01

    Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. γ-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by γ-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given PB than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver. (author)

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

    Science.gov (United States)

    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.

  1. Glutamyl aminopeptidase in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats.

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    Andrés Quesada

    Full Text Available The aim of this work was to investigate if the content of glutamyl aminopeptidase (GluAp in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats.Urine samples were collected 24 hours after injection of cisplatin (7 mg/kg, n = 10 or saline serum (n = 10, and they were subjected to differential centrifugation at 1.000, 17.000 and 200.000 g to obtain microvesicular and exosomal fractions. GluAp was measured with a commercial ELISA kit in both fractions. Serum creatinine (SCr and body weight were measured 15 days after treatment. We analyzed if early excretion of GluAp in microsomal and exosomal fractions was correlated with final SCr and body weight increase. In a second experiment, enzymatic activities of GluAp and alanyl aminopeptidase (AlaAp in urine, microvesicular and exosomal fractions were measured three days after injection. We analyzed the correlation of both markers with SCr determined at this point. Finally, we studied the expression of GluAp and extracellular vesicles markers Alix and tumor susceptibility gene (TSG101 in both fractions by immunoblotting.GluAp excretion was increased in all fractions of urine after cisplatin treatment, even if data were normalized per mg of creatinine, per body weight or per total protein content of each fraction. We found significant predictive correlations with SCr concentration, and inverse correlations with body weight increase determined 15 days later. Three days after injection, aminopeptidasic activities were markedly increased in all fractions of urine in cisplatin-treated rats. The highest correlation coefficient with SCr was found for GluAp in microvesicular fraction. Increase of GluAp in microvesicular and exosomal fractions from cisplatin-treated rats was confirmed by immunoblotting. Alix and TSG101 showed different patterns of expression in each fraction.Determination of GluAp content or its enzymatic activity in microvesicular and

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

    International Nuclear Information System (INIS)

    Wuest, F.; Hultsch, C.; Bergmann, R.; Johannsen, B.; Henle, T.

    2003-01-01

    The isopeptide N ε -(γ-glutamyl)-L-lysine 4 was labelled with 18 F via N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB). A modified approach for the convenient synthesis of [ 18 F]SFB was used, and [ 18 F]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 ε -(γ-glutamyl)-L-lysine with [ 18 F]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 1.3 GBq of [ 18 F]SFB could be converted into 447 MBq (46%, decay-corrected) of [ 18 F]fluorobenzoylated isopeptide within 45 min, including HPLC purification

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-01

    The isopeptide N{sup {epsilon}}-({gamma}-glutamyl)-L-lysine 4 was labelled with {sup 18}F via N-succinimidyl-4-[{sup 18}F]fluorobenzoate ([{sup 18}F]SFB). A modified approach for the convenient synthesis of [{sup 18}F]SFB was used, and [{sup 18}F]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{sup {epsilon}}-({gamma}-glutamyl)-L-lysine with [{sup 18}F]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 1.3 GBq of [{sup 18}F]SFB could be converted into 447 MBq (46%, decay-corrected) of [{sup 18}F]fluorobenzoylated isopeptide within 45 min, including HPLC purification.

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

    Science.gov (United States)

    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.

  5. Use of serum gamma glutamyl transferase as a biomarker of stress and metabolic dysfunctions in Rathi cattle of arid tract in India

    Directory of Open Access Journals (Sweden)

    Kataria N.

    2012-08-01

    Full Text Available The investigation was carried out to determine serum gamma glutamyl transferase enzyme as a biomarker of stress and metabolic dysfunctions in Rathi cattle of arid tract in India. Blood samples were collected to harvest serum from healthy male and female, drought affected, ketotic cows, recently aborted cows, cows with diarrhoea, cows with traumatic pericarditis, calves with urinary calculi, cows affected with urea poisoning and cows affected with acidosis. The mean values of γ glutamyl transferase showed significant variations (p≤0.05 according to sex and age in the healthy group of animals. The normal range in healthy animals was from 12 to 34 UL-1. In affected group an average 23.69 times rise in the value was observed from that of healthy group. Cows affected with urea poisoning and acidosis were having highest mean values whereas drought affected animals were having least value. It was concluded that present study attempted to provide a new insight about an old enzyme. As the number of animals in the present study was statistically sufficient therefore the mean value of healthy group can be used as reference value for γ GT in Rathi cattle and other cattle breeds which can help to interpret the variations of serum γ GT in various metabolic diseases of cattle.

  6. Serum lipid peroxidation level as a fine predictor for hepatocyte in jury and disease activity in patients with non-alcoholic fatty liver disease%非酒精性脂肪性肝病患者血清脂质过氧化指标对血清转氨酶升高程度的预测评价

    Institute of Scientific and Technical Information of China (English)

    宁波; 韩昕晶; 沈薇

    2011-01-01

    别收集血清进行丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、谷酰转肽酶(Gamma-glutamyl transpeptidase,GGT)水平检测以及血糖、血脂、身高、体重、腰围、臀围等测定,同时检测GSH、GSSG及MDA水平进行分析.结果:NAFLD患者血清中GSSG及MDA含量比对照组明显升高,而GSH比正常对照显著降低.多元线性回归分析结果表明MDA、GSSG、GSH及GSH/GSSG对NAFLD患者血清转氨酶ALT、AST影响具有显著意义(β值分别为0.324、0.961、-0.365、0.592以及0.400、0.951、-0.396,0.7).对GGT影响显著的因素是GSSG和MDA(β值分别为0.812、0.628),GSH及GSH/GSSG对GGT的影响没有显著性.结论:NAFLD患者血清脂质过氧化指标的水平与血清转氨酶水平密切相关.在肝细胞损伤过程中,血清MDA、GSSG及GSH/GSSG水平异常早于血清转氨酶,能够作为反映NAFLD患者肝细胞受损的敏感的血清学指标.

  7. Experimental Protoporphyria: Effect of Bile Acids on Liver Damage Induced by Griseofulvin

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    María del Carmen Martinez

    2015-01-01

    Full Text Available The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA, dehydrocholic (DHA, chenodeoxycholic, or ursodeoxycholic (URSO. The administration of Gris alone increased the activities of glutathione reductase (GRed, superoxide dismutase (SOD, alkaline phosphatase (AP, gamma glutamyl transpeptidase (GGT, and glutathione-S-transferase (GST, as well as total porphyrins, glutathione (GSH, and cytochrome P450 (CYP levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris.

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

    Science.gov (United States)

    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. INCREASE OF GLYCOSAMINOGLYCANS AND METALLOPROTEINASES 2 AND 9 IN LIVER EXTRACELLULAR MATRIX ON EARLY STAGES OF EXTRAHEPATIC CHOLESTASIS

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    Pedro Luiz Rodrigues GUEDES

    2014-12-01

    Full Text Available Context Cholestasis produces hepatocellular injury, leukocyte infiltration, ductular cells proliferation and fibrosis of liver parenchyma by extracellular matrix replacement. Objective Analyze bile duct ligation effect upon glycosaminoglycans content and matrix metalloproteinase (MMPs activities. Methods Animals (6-8 weeks; n = 40 were euthanized 2, 7 or 14 days after bile duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT, alkaline phosphatase (Alk-P, alanine and aspartate aminotransferases (ALT and AST, tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities, histopathology and glycosaminoglycans content. Results Cholestasis caused cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was neutrophil infiltration observed by the increasing of myeloperoxidase activity on 7 (P = 0.0064 and 14 (P = 0.0002 groups which leads to the magnification of tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667, MMP-2 (P = 0.0003 and MMP-9 (P<0.0001 activities on 14 days indicating matrix remodeling and establishment of inflammatory process. Bile duct ligation animals showed an increasing on dermatan sulfate and/or heparan sulfate content reflecting extracellular matrix production and growing mitosis due to parenchyma depletion. Conclusions Cholestasis led to many changes on rats’ liver parenchyma, as so as on its extracellular matrix, with major alterations on MMPs activities and glycosaminoglycans content.

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

    Directory of Open Access Journals (Sweden)

    Mansour S. Al-Said

    2016-01-01

    Full Text Available 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.

  11. Antimicrobial activities of isothiocyanates against Campylobacter jejuni isolates

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    Virginie eDufour

    2012-04-01

    Full Text Available 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.Both AITC and BITC displayed a potent antibacterial activity against C. jejuni. BITC showed a higher overall antibacterial effect (MIC of 2.5 to 5 g mL-1 compared to AITC (MIC of 50 to 200 g mL-1. Interestingly, the 24 C. jejuni isolates could be classified in 3 groups according to their sensitivity levels to both compounds, suggesting that AITC and BITC shared identical activity mechanisms and consequently faced similar resistance processes in bacterial cells.The sensitivity levels of C. jejuni strains against isothiocyanates were neither correlated with the presence of a GGT (-Glutamyl Transpeptidase encoding gene in the genome nor with the origin of the biological sample. However the ggt mutant of C. jejuni 81-176 displayed a decreased survival rate compared to WT when exposed to ITC.

  12. Routine testing of liver function before and after elective laparoscopic cholecystectomy: is it necessary?

    LENUS (Irish Health Repository)

    Ahmad, Nasir Zaheer

    2012-01-31

    BACKGROUND AND OBJECTIVES: Liver function tests (LFTs) include alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and bilirubin. The role of routine testing before and after laparoscopic cholecystectomy was evaluated in this study. PATIENTS AND METHODS: A total of 355 patients were retrospectively analyzed by examining the LFTs the day before, the day after, and 3 weeks after the surgery. The Wilcoxon signed-rank test and Student t test were performed to determine statistical significance. RESULTS: Alterations in the serum AST, ALT, and GGT were seen on the first postoperative day. Minor changes were seen in bilirubin and ALP. An overall disturbance in the LFTs was seen in more than two-thirds of the cases. Repeat LFTs performed after 3 weeks on follow-up were found to be within normal limits. CONCLUSION: Mild-to-moderate elevation in preoperative LFTs may not be associated with any deleterious effect, and, in the absence of clinical indications, routine preoperative or postoperative liver function testing is unnecessary.

  13. RESPOSTAS DE BIOMARCADORES MUSCULARES A UMA PARTIDA DE FUTEBOL

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    Jader de Andrade Bezerra

    2014-04-01

    Full Text Available Exhausting physical exercise damages muscular tissue. Among other factors, damage depends on training load and intensity. The aim of this study was to determine changes in enzymatic biomarkers in response to a football match. The study sample was composed of 30 football players aged between 18–35 years and male, divided into experimental (GE; N = 15 and control (GC; N = 15 groups. Blood samples from GE and GC individuals were withdrawn before and 24 hours after the match. The following enzymes were examined: total creatine kinase (CKt, cardiac muscle creatine kinase (CKMB, lactate dehydrogenase (LDH, and gamma-glutamyl transpeptidase (GGT. In GE individuals, there were significant changes (p<0.05 in CKt (334±203 and 860±553 U/L, CKMB (30±7 and 42±11 U/L, and LDH (417±86 and 547±84 U/L between before and after the match, respectively; GGT remained unchanged. In GC individuals, levels were similar at the two time points. A football game is sufficiently aggressive to induce tissue damage, as evidenced by increased plasma levels of various enzymes. Enzyme clearance assessment might be a valuable tool for development of training programs.

  14. 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.

    Science.gov (United States)

    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

  15. Chloroplast SRP43 acts as a chaperone for glutamyl-tRNA reductase, the rate-limiting enzyme in tetrapyrrole biosynthesis.

    Science.gov (United States)

    Wang, Peng; Liang, Fu-Cheng; Wittmann, Daniel; Siegel, Alex; Shan, Shu-Ou; Grimm, Bernhard

    2018-04-10

    Assembly of light-harvesting complexes requires synchronization of chlorophyll (Chl) biosynthesis with biogenesis of light-harvesting Chl a/b-binding proteins (LHCPs). The chloroplast signal recognition particle (cpSRP) pathway is responsible for transport of nucleus-encoded LHCPs in the stroma of the plastid and their integration into the thylakoid membranes. Correct folding and assembly of LHCPs require the incorporation of Chls, whose biosynthesis must therefore be precisely coordinated with membrane insertion of LHCPs. How the spatiotemporal coordination between the cpSRP machinery and Chl biosynthesis is achieved is poorly understood. In this work, we demonstrate a direct interaction between cpSRP43, the chaperone that mediates LHCP targeting and insertion, and glutamyl-tRNA reductase (GluTR), a rate-limiting enzyme in tetrapyrrole biosynthesis. Concurrent deficiency for cpSRP43 and the GluTR-binding protein (GBP) additively reduces GluTR levels, indicating that cpSRP43 and GBP act nonredundantly to stabilize GluTR. The substrate-binding domain of cpSRP43 binds to the N-terminal region of GluTR, which harbors aggregation-prone motifs, and the chaperone activity of cpSRP43 efficiently prevents aggregation of these regions. Our work thus reveals a function of cpSRP43 in Chl biosynthesis and suggests a striking mechanism for posttranslational coordination of LHCP insertion with Chl biosynthesis.

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

    Science.gov (United States)

    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.

  17. Partial suppression of the respiratory defect of qrs1/her2 glutamyl-tRNA amidotransferase mutants by overexpression of the mitochondrial pentatricopeptide Msc6p.

    Science.gov (United States)

    Moda, Bruno S; Ferreira-Júnior, José Ribamar; Barros, Mario H

    2016-08-01

    Recently, a large body of evidences indicates the existence in the mitochondrial matrix of foci that contain different proteins involved in mitochondrial RNA metabolism. Some of these proteins have a pentatricopeptide repeat motif that constitutes their RNA-binding structures. Here we report that MSC6, a mitochondrial pentatricopeptide protein of unknown function, is a multi copy suppressor of mutations in QRS1/HER2 a component of the trimeric complex that catalyzes the transamidation of glutamyl-tRNAQ to glutaminyl-tRNAQ. This is an essential step in mitochondrial translation because of the lack of a specific mitochondrial aminoacyl glutaminyl-tRNA synthetase. MSC6 over-expression did not abolish translation of an aberrant variant form of Cox2p detected in QRS1/HER2 mutants, arguing against a suppression mechanism that bypasses Qrs1p function. A slight decrement of the mitochondrial translation capacity as well as diminished growth on respiratory carbon sources media for respiratory activity was observed in the msc6 null mutant. Additionally, the msc6 null mutant did not display any impairment in RNA transcription, processing or turnover. We concluded that Msc6p is a mitochondrial matrix protein and further studies are required to indicate the specific function of Msc6p in mitochondrial translation.

  18. Simple serum markers for significant liver inflammation in chronic hepatitis B patients with an alanine aminotransferase level lower than 2 times upper limit of normal

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    LI Qiang

    2016-06-01

    Full Text Available ObjectiveTo investigate the simple serum markers for significant liver inflammation in chronic hepatitis B (CHB patients with an alanine aminotransferase (ALT level of <2 times upper limit of normal (ULN. MethodsThe clinical data of 278 CHB patients with ALT <2×ULN (ULN=40 U/L were analyzed retrospectively. Significant liver inflammation was defined as a liver inflammatory activity grade (G ≥2. The t-test was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis rank sum test was used for non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. Multivariate logistic regression analysis was used to identify independent predictors for significant liver inflammation in CHB patients with ALT <2×ULN. The receiver operating characteristic (ROC curve was used to evaluate the diagnostic value of serum markers in significant liver inflammation. ResultsOf the 278 CHB patients enrolled, 175 (62.9% had no significant liver inflammation (G0-1 group and 103 (37.1% had significant liver inflammation (G2-4 group. There were significant differences in ALT, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT, albumin, globulin, prothrombin time (PT, platelet, absolute neutrophil count, hyaluronic acid (HA, glycocholic acid, precollagen Ⅲ, and collagen type Ⅳ(ⅣC between the two groups (all P<0.05. The multivariate regression analysis showed that GGT, PT, ⅣC, and HA were independent predictors for significant liver inflammation in CHB patients with ALT<2×ULN (OR=1.015, 1.600, 1.151, and 1.014, P=0.008, 0.021, 0.003, and 0.018. The areas under the ROC curve for GGT, PT, IVC, and HA to diagnose significant liver inflammation were 0.804, 0.722, 0.707, and 0.632, respectively. The cut-off value of 48.5 U/L for GGT to predict significant liver inflammation had a specificity of 90.3% and a negative

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

    Science.gov (United States)

    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.

  20. Analysis of the peptidoglycan hydrolase complement of Lactobacillus casei and characterization of the major γ-D-glutamyl-L-lysyl-endopeptidase.

    Science.gov (United States)

    Regulski, Krzysztof; Courtin, Pascal; Meyrand, Mickael; Claes, Ingmar J J; Lebeer, Sarah; Vanderleyden, Jos; Hols, Pascal; Guillot, Alain; Chapot-Chartier, Marie-Pierre

    2012-01-01

    Peptidoglycan (PG) is the major component of Gram positive bacteria cell wall and is essential for bacterial integrity and shape. Bacteria synthesize PG hydrolases (PGHs) which are able to cleave bonds in their own PG and play major roles in PG remodelling required for bacterial growth and division. Our aim was to identify the main PGHs in Lactobacillus casei BL23, a lactic acid bacterium with probiotic properties.The PGH complement was first identified in silico by amino acid sequence similarity searches of the BL23 genome sequence. Thirteen PGHs were detected with different predicted hydrolytic specificities. Transcription of the genes was confirmed by RT-PCR. A proteomic analysis combining the use of SDS-PAGE and LC-MS/MS revealed the main seven PGHs synthesized during growth of L. casei BL23. Among these PGHs, LCABL_02770 (renamed Lc-p75) was identified as the major one. This protein is the homolog of p75 (Msp1) major secreted protein of Lactobacillus rhamnosus GG, which was shown to promote survival and growth of intestinal epithelial cells. We identified its hydrolytic specificity on PG and showed that it is a γ-D-glutamyl-L-lysyl-endopeptidase. It has a marked specificity towards PG tetrapeptide chains versus tripeptide chains and for oligomers rather than monomers. Immunofluorescence experiments demonstrated that Lc-p75 localizes at cell septa in agreement with its role in daughter cell separation. It is also secreted under an active form as detected in zymogram. Comparison of the muropeptide profiles of wild type and Lc-p75-negative mutant revealed a decrease of the amount of disaccharide-dipeptide in the mutant PG in agreement with Lc-p75 activity. As a conclusion, Lc-p75 is the major L. casei BL23 PGH with endopeptidase specificity and a key role in daughter cell separation. Further studies will aim at investigating the role of Lc-p75 in the anti-inflammatory potential of L. casei BL23.

  1. Analysis of the peptidoglycan hydrolase complement of Lactobacillus casei and characterization of the major γ-D-glutamyl-L-lysyl-endopeptidase.

    Directory of Open Access Journals (Sweden)

    Krzysztof Regulski

    Full Text Available Peptidoglycan (PG is the major component of Gram positive bacteria cell wall and is essential for bacterial integrity and shape. Bacteria synthesize PG hydrolases (PGHs which are able to cleave bonds in their own PG and play major roles in PG remodelling required for bacterial growth and division. Our aim was to identify the main PGHs in Lactobacillus casei BL23, a lactic acid bacterium with probiotic properties.The PGH complement was first identified in silico by amino acid sequence similarity searches of the BL23 genome sequence. Thirteen PGHs were detected with different predicted hydrolytic specificities. Transcription of the genes was confirmed by RT-PCR. A proteomic analysis combining the use of SDS-PAGE and LC-MS/MS revealed the main seven PGHs synthesized during growth of L. casei BL23. Among these PGHs, LCABL_02770 (renamed Lc-p75 was identified as the major one. This protein is the homolog of p75 (Msp1 major secreted protein of Lactobacillus rhamnosus GG, which was shown to promote survival and growth of intestinal epithelial cells. We identified its hydrolytic specificity on PG and showed that it is a γ-D-glutamyl-L-lysyl-endopeptidase. It has a marked specificity towards PG tetrapeptide chains versus tripeptide chains and for oligomers rather than monomers. Immunofluorescence experiments demonstrated that Lc-p75 localizes at cell septa in agreement with its role in daughter cell separation. It is also secreted under an active form as detected in zymogram. Comparison of the muropeptide profiles of wild type and Lc-p75-negative mutant revealed a decrease of the amount of disaccharide-dipeptide in the mutant PG in agreement with Lc-p75 activity. As a conclusion, Lc-p75 is the major L. casei BL23 PGH with endopeptidase specificity and a key role in daughter cell separation. Further studies will aim at investigating the role of Lc-p75 in the anti-inflammatory potential of L. casei BL23.

  2. Multifunctional non-viral gene vectors with enhanced stability, improved cellular and nuclear uptake capability, and increased transfection efficiency

    Science.gov (United States)

    Yang, Zhe; Jiang, Zhaozhong; Cao, Zhong; Zhang, Chao; Gao, Di; Luo, Xingen; Zhang, Xiaofang; Luo, Huiyan; Jiang, Qing; Liu, Jie

    2014-08-01

    We have developed a new multifunctional, non-viral gene delivery platform consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG shell for nanoparticle stabilization, poly(γ-glutamic acid) (γ-PGA) and mTAT (a cell-penetrating peptide) for accelerated cellular uptake, and a nuclear localization signal peptide (NLS) for enhanced intracellular transport of DNA to the nucleus. In vitro study showed that coating of the binary PPMS/DNA polyplex with γ-PGA promotes cellular uptake of the polyplex particles, particularly by γ-glutamyl transpeptidase (GGT)-positive cells through the GGT-mediated endocytosis pathway. Conjugating PEG to the γ-PGA led to the formation of a ternary PPMS/DNA/PGA-g-PEG polyplex with decreased positive charges on the surface of the polyplex particles and substantially higher stability in serum-containing aqueous medium. The cellular uptake rate was further improved by incorporating mTAT into the ternary polyplex system. Addition of the NLS peptide was designed to facilitate intracellular delivery of the plasmid to the nucleus--a rate-limiting step in the gene transfection process. As a result, compared with the binary PPMS/LucDNA polyplex, the new mTAT-quaternary PPMS/LucDNA/NLS/PGA-g-PEG-mTAT system exhibited reduced cytotoxicity, remarkably faster cellular uptake rate, and enhanced transport of DNA to the nucleus. All these advantageous functionalities contribute to the remarkable gene transfection efficiency of the mTAT-quaternary polyplex both in vitro and in vivo, which exceeds that of the binary polyplex and commercial Lipofectamine™ 2000/DNA lipoplex. The multifunctional mTAT-quaternary polyplex system with improved efficiency and reduced cytotoxicity represents a new type of promising non-viral vectors for the delivery of therapeutic genes to treat tumors.We have developed a new multifunctional, non-viral gene delivery platform consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG shell

  3. Antiobesity, antioxidant and antidiabetic activities of red Ginseng plant extract in obese diabetic rats

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    Mostafa Abbas Shalaby

    2013-06-01

    Full Text Available Aim: This study aimed to investigate the effects of red ginseng extract (RGE on adiposity index, some serum biochemical parameters and tissue antioxidant activity in obese diabetic rats. Materials and Methods: Five groups of male Sprague-Dawley rats were used. Group (1 was negative control and the other 4 groups were fed on high fat-diet for 6 weeks to induce obesity. The obese rats were then rendered diabetic by intraperitoneal injection of alloxan for 5 days. Group (2 was kept obese diabetic (positive control and the other 3 groups were orally given RGE at 100, 200 and 400 mg /kg /day, respectively, for 4 weeks. Blood samples were collected for biochemical analyses and kidneys were taken to assay of activities of antioxidant enzymes. Results: oral dosage of RGE to obese diabetic rats significantly (P < 0.05 reduced adiposity index; decreased serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, gamma- glutamyl transpeptidase (GGT enzymes, total cholesterol (TC, triglycerides (TG, and low density lipoproteins (LDL-c and improved atherogenic index. Blood glucose and leptin hormone decreased, but insulin increased by administration of RGE. it increased activities of superoxide dismutase (SOD, glutathione peroxidase (GPx and catalase (CAT antioxidant enzymes in kidneys tissues. Conclusion: Red ginseng extract produces antiobesity, antioxidant, and antidiabetic activities in obese diabetic rats. The study suggests that red ginseng plant may be beneficial for the treatment of patients who suffer from obesity associated with diabetes. [J Intercult Ethnopharmacol 2013; 2(3.000: 165-172

  4. Synthesis and Bactericidal Properties of Hyaluronic Acid Doped with Metal Nanoparticles

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    Galo Cárdenas-Triviño

    2017-01-01

    Full Text Available A study on the nanoparticles size and the antibacterial properties of hyaluronic acid (HA doped with nanoparticles is reported. Nanoparticles from gold, silver, copper, and silver palladium with HA support were performed. The solvated metal atom dispersion (SMAD method with 2-propanol and HA was used. High-resolution transmission electron microscopy (HRTEM, infrared spectroscopy (FT-IR, and thermogravimetric analysis (TGA were conducted. The average sizes of nanoclusters were as follows: HA-Au = 17.88 nm; HA-Ag = 50.41 nm; HA-Cu = 13.33 nm; and HA-AgPd = 33.22 nm. The antibacterial activity of solutions and films containing nanoparticles against American Type Culture Collection (ATCC bacterial strains Escherichia coli (EC, Staphylococcus aureus (SA, Staphylococcus epidermidis (SE, and Pseudomonas aeruginosa (PA was determined. Inhibition was observed for HA-Ag, HA-Cu, and HA-AgPd. Toxicological tests were performed in rats that were injected intraperitoneally with two concentrations of gold, copper, silver, and silver-palladium nanoparticles. No alterations in hepatic parameters, including ALT (alanine aminotransferase, GGT (gamma-glutamyl transpeptidase bilirubin, and albumin, were observed after 14 days. These films could be used as promoters of skin recovery and Grades I and II cutaneous burns and as scaffolds.

  5. Seasonal variation in haematological and biochemical variables in free-ranging subadult brown bears (Ursus arctos) in Sweden.

    Science.gov (United States)

    Græsli, Anne Randi; Evans, Alina L; Fahlman, Åsa; Bertelsen, Mads F; Blanc, Stéphane; Arnemo, Jon M

    2015-12-08

    Free-ranging brown bears exhibit highly contrasting physiological states throughout the year. They hibernate 6 months of the year, experiencing a decrease in body temperature, heart rate, respiratory rate and metabolism. An increase in food consumption and the resulting weight gain (mostly through fat storage) prior to hibernation are also part of the brown bear's annual cycle. Due to these physiological changes, haematological and biochemical variables vary dramatically throughout the year. Seasonal changes in 12 haematological and 34 biochemical variables were evaluated in blood samples collected from 40 free-ranging subadult brown bears (22 females, 18 males) immobilised in Sweden in winter (February-March), spring (April-May), and summer (June). Higher levels of haemoglobin, haematocrit and red blood cell count, and a lower white blood cell count and mean cell volume was found during hibernation than in spring and summer. Lower values of the enzymes; aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), γ-glutamyl transpeptidase (GGT), glutamate dehydrogenase (GD) and amylase, and increased values of β-hydroxybutyrate (β-HBA) and blood lipids; triglycerides, cholesterol and free fatty acids, were present during hibernation compared to spring and summer. This study documents significant shifts in haematological and biochemical variables in samples collected from brown bears anaesthetised in winter (February-March) compared to in spring and summer (April-June), reflecting the lowered metabolic, renal and hepatic activity during hibernation. Lower values of enzymes and higher values of blood lipids during hibernation, likely reflect a lipid-based metabolism.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-α Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury

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    Jing-Hua Peng

    2012-01-01

    Full Text Available Kudzu (Pueraria lobata is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. However, little is known about its effects on chronic alcoholic liver injury. Therefore, the present study observed the effects of puerariae radix extract (RPE on chronic alcoholic liver injury as well as Kupffer cells (KCs activation to release tumor necrosis factor alpha (TNF-α induced by gut-derived endotoxin in rats and macrophage cell line. RPE was observed to alleviate the pathological changes and lipids deposition in liver tissues as well as the serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, and hepatic gamma-glutamyl transpeptidase (GGT activity. Meanwhile, RPE inhibited KCs activation and subsequent hepatic TNF-α expression and downregulated the protein expression of endotoxin receptors, lipopolysaccharide binding protein (LBP, CD14, Toll-like receptor (TLR 2, and TLR4 in chronic alcohol intake rats. Furthermore, an in vitro study showed that RPE inhibited the expression of TNF-α and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells. In summary, this study demonstrated that RPE mitigated liver damage and lipid deposition induced by chronic alcohol intake in rats, as well as TNF-α release, protein expression of endotoxin receptors in vivo or in vitro.

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

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    Salonen Hanna

    2007-01-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 CLD compared to control group (0.0714 ± 0.0283) with a p-value of 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kukuk, Guido M.; Schaefer, Stephanie G.; Hadizadeh, Dariusch R.; Schild, Hans H.; Willinek, Winfried A. [University of Bonn, Department of Radiology, Bonn (Germany); Fimmers, Rolf [University of Bonn, Department of Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Ezziddin, Samer [Department of Nuclear Medicine, Bonn (Germany); Spengler, Ulrich [Department of Internal Medicine I, Bonn (Germany)

    2014-10-15

    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 valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. (orig.)

  15. Mutation detection in cholestatic patients using microarray resequencing of ATP8B1 and ABCB11 [v2; ref status: indexed, http://f1000r.es/yv

    Directory of Open Access Journals (Sweden)

    Kirsten E McKay

    2013-03-01

    Full Text Available Background: Neonatal cholestasis is a common presentation of childhood liver diseases and can be a feature of various conditions including disorders of bile acid biogenesis and transport, various inborn errors of metabolism and perinatal infections. Some inherited metabolic diseases can be easily screened using biochemical assays, however many can only be accurately diagnosed by DNA sequencing. Fluorescent capillary Sanger sequencing (FS is the gold standard method used by clinical laboratories for genetic diagnosis of many inherited conditions; however, it does have limitations. Recently microarray resequencing (MR has been introduced into research and clinical practice as an alternative method for genetic diagnosis of heterogeneous conditions. In this report we compared the accuracy of mutation detection for MR with FS in a group of patients with ‘low-normal’ gamma glutamyl transpeptidase (gGT cholestasis without known molecular diagnoses. Methods: 29 patient DNA samples were tested for mutations in the ATP8B1 and ABCB11 genes using both FS and MR. Other known causes of “low gGT cholestasis” such as ARC syndrome and bile acid biosynthesis disorders were excluded. Results: Mutations were identified in 13/29 samples. In 3/29 samples FS and MR gave discordant results: MR had a false positive rate of 3.4% and a false negative rate of 7%. Conclusions: The major advantage of MR over FS is that multiple genes can be screened in one experiment, allowing rapid and cost-effective diagnoses.  However, we have demonstrated that MR technology is limited in sensitivity. We therefore recommend that MR be used as an initial evaluation, with FS deployed when genetic and clinical or histopathological findings are discordant.

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

    Science.gov (United States)

    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.

  17. Influence of dietary fat and selenium fed during initiation or promotion on the development of preneoplastic lesions in rat liver

    International Nuclear Information System (INIS)

    Baldwin, S.; Parker, R.S.

    1986-01-01

    Aflatoxin B 1 (AFB1)-induced γ-glutamyl transpeptidase (GGT)-positive foci in rat liver were assessed in animals fed different levels of fat and selenium (Se) during either initiation (IN) or promotion (PR). Male Sprague Dawley rats (50g) were divided into 12 groups. One of six modified AIN-76 experimental diets were fed to groups 1-6 during weeks 1-4.5 (IN) and to groups 7-12 during weeks 4.5-15 (PR). During weeks 3-4, 13 rats/group received 10 daily doses of AFB1 (.4 mg/kg bwt/dose, i.g.). Two levels of corn oil (2% and 20%) were fed, each containing 3 levels of Se: < 0.02; 0.15; 2.5 (IN) or 1.9 (PR) ppm. When not fed the experimental diets rats were fed a standard AIN-76 diet. In groups 1-6, 0.03% phenobarbital was added to the standard diet. At week 15 rats were sacrificed. Compared to all low-fat groups, the high-fat diets with either < 0.02 or 0.15 ppm Se fed during IN resulted in a marked increase in mean diameter of GGT-positive foci and % liver section occupied by foci. In rats fed high-fat 2.5 ppm Se, preneoplastic development was decreased below all low-fat groups. During PR, Se status but not dietary fat level influenced foci formation. Rats fed < 0.02 ppm Se had greater mean diameter of foci and % section occupied by foci than either 0.15 or 1.9 ppm Se. Thus, an interaction was observed between dietary fat and selenium during IN, but not during PR

  18. Causal mediation analysis with multiple mediators.

    Science.gov (United States)

    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.

  19. Nanosecond pulsed electric field (nsPEF) disrupts the structure and metabolism of human Echinococcus granulosus protoscolex in vitro with a dose effect.

    Science.gov (United States)

    Zhang, Ruiqing; Aji, Tuerganaili; Shao, Yingmei; Jiang, Tiemin; Yang, Lei; Lv, Weimin; Chen, Yonggang; Chen, Xinhua; Wen, Hao

    2017-04-01

    The number of interventional treatments for hepatic cystic echinococcosis is increasing, but the chemicals or high temperatures used in these methodologies cause biliary complications, thus limiting their clinical applications. This experimental study aimed to apply a novel, non-thermal, non-chemical ablation method termed nanosecond pulsed electric field (nsPEF) for the treatment of human hepatic cystic echinococcosis. The nsPEF treatment parameters against protoscolices from human hepatic cystic echinococcosis were optimized in vitro. The efficacy and mechanism of nsPEF treatment were also investigated. Fresh protoscolices were isolated from human hepatic cystic echinococcosis and were exposed to 300 ns of nsPEF with different field strengths (0, 7, 14, 21, and 29 kV/cm) and pulse numbers (50 and 100 pulses). Then, the viability of the nsPEF-treated protoscolices was evaluated in vitro. Morphological and ultra-structural changes were visualized with H&E staining and scanning electron microscopy. The membrane enzyme activity of alkaline phosphatase (AP) and gamma-glutamyl-transpeptidase (GGT) was measured. nsPEF caused dose-dependent protoscolex death. One-hundred pulses of nsPEF at 21 kV/cm or higher caused a significant increase in the death rate of protoscolices. nsPEF induced significant lethal damage with 50 pulses at 21 or 29 kV/cm and with 100 pulses at 14, 21, or 29 kV/cm, accompanied by morphological destruction and increased levels of AP and GGT membrane enzymes. Thus, nsPEF induced dose-dependent protoscolex mortality and caused destruction of protoscolices and increased membrane enzymes. The mechanism may involve direct damage to the membrane structures of the protoscolices, promoting enzyme exhaustion and disruption of metabolism.

  20. Oral toxicity study of tragacanth gum in B6C3F1 mice: development of squamous-cell hyperplasia in the forestomach and its reversibility.

    Science.gov (United States)

    Hagiwara, A; Tanaka, H; Tiwawech, D; Shirai, T; Ito, N

    1991-10-01

    Tragacanth gum was administered at dietary levels of 0 (control), 0.625, 1.25, 2.5, and 5.0% to groups of 10 male and 10 female B6C3F1 mice for 13 wk. There were no treatment-associated effects regarding clinical signs, body or organ weights, and urinalysis or hematology data. Significant dose-related, but slight, elevations of plasma gamma-glutamyl transpeptidase (GGT) level were observed in all treated animals except the 0.625% females. Single or small numbers of tiny nodules were observed on the luminal surface of the forestomach in 4 males of the 5.0% group, 2 males of the 2.5% group, and 1 male each from the 1.25 and 0.625% groups. Histopathologically, they were diagnosed as squamous-cell hyperplasia. To investigate the nature of these gross lesions, tragacanth gum was fed to groups of 30 male mice at the dietary level of 5.0% for periods of up to 48 wk; 20 males served as controls. There were no treatment-related increases of plasma GGT levels at wk 24 and 48. Although squamous-cell hyperplasias were seen in 2 out of 10 mice at wk 24, none of these proliferative lesions were apparent at wk 48, after either chronic exposure or 24 wk on basal diet. Furthermore, the levels of DNA synthesis in forestomach epithelium as measured by 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry were comparable to control values at wk 24 and 48. Thus, the oral toxicity of tragacanth gum to B6C3F1 mice was concluded to be negligible.

  1. Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

    International Nuclear Information System (INIS)

    Mansonr, S.Z.

    2009-01-01

    Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

  2. Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

    International Nuclear Information System (INIS)

    Mansonr, S.Z.

    2008-01-01

    Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

  3. Clinical experience with ursodeoxycholic acid (Urdoxa in complex therapy of chronic viral hepatitis

    Directory of Open Access Journals (Sweden)

    E. V. Esaulenko

    2011-01-01

    Full Text Available Patients with chronic virus hepatitis (32 patients, 13 with chronic hepatitis B and 19 with chronic hepatitis C ages from 20 to 72 with elevated levels of bilirubin and active alanine aminotransferase, aspartate aminotransferase, gamma- glutamyl transpeptidase, received ursodeoxycholic acid (Urdoxa over the course of 12 weeks. During therapy alanine aminotransferase, aspartate aminotransferase, bilirubin and gamma-glutamyl transpeptidase levels decreased. Urdoxa demonstrated good tolerance, efficacy and no visible side effects. Thus, Urdoxa could be used in treatment of chronic viral hepatitis with cytolytic and cholestatic syndromes.

  4. Associations of Insulin Resistance and Glycemia With Liver Enzymes in Hispanic/Latino Youths: Results From the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth).

    Science.gov (United States)

    Parrinello, Christina M; Rudolph, Bryan J; Lazo, Mariana; Gallo, Linda C; Thyagarajan, Bharat; Cotler, Scott J; Qi, Qibin; Seeherunvong, Tossaporn; Vidot, Denise C; Strickler, Howard D; Kaplan, Robert C; Isasi, Carmen R

    2017-11-03

    Associations of insulin resistance and hyperglycemia with a panel of liver enzymes have not been well studied in a young, heterogenous Hispanic/Latino population. We aimed to assess the associations of insulin resistance and glycemia with nonalcoholic fatty liver disease (NAFLD), as measured by liver enzymes and the pediatric NAFLD fibrosis index (PNFI), and whether these associations are modified by body mass index and mediated by inflammation or endothelial dysfunction. We conducted a cross-sectional study of 1317 boys and girls aged 8 to 16 years from the Hispanic Community Children's Health Study/Study of Latino Youth. We used Poisson regression to assess the associations of fasting glucose, hemoglobin A1c, and homeostasis model assessment of insulin resistance (HOMA-IR) with elevated alanine aminotransferase (ALT) (>25 U/L in boys, >22 U/L in girls), aspartate aminotransferase (AST) (≥37 U/L), gamma-glutamyl transpeptidase (GGT) (≥17 U/L), and PNFI (≥9; a function of age, waist circumference, and triglyceride level). HOMA-IR was associated with elevated ALT, AST, GGT, and PNFI [prevalence ratios (95% confidence intervals) for each 1-unit increase in the natural log of HOMA-IR: 1.99 (1.40-2.81), 2.15 (1.12-4.12), 1.70 (1.26-2.30), and 1.98 (1.43-2.74), respectively]. Associations were observed in overweight/obese children, but not in normal weight children (P-interaction=0.04 for AST and P-interaction=0.07 for GGT). After further adjustment for adiponectin, high-sensitivity C-reactive protein, e-selectin, and PAI-1, associations of HOMA-IR with liver enzymes and PNFI were attenuated, but remained statistically significant for AST and PNFI. Insulin resistance was associated with NAFLD in overweight/obese Hispanic/Latino youth, and this association may be partially mediated by inflammation and endothelial dysfunction.

  5. Comparison of different initiation protocols in the resistant hepatocyte model

    International Nuclear Information System (INIS)

    Espandiari, Parvaneh; Robertson, Larry W.; Srinivasan, Cidambi; Glauert, Howard P.

    2005-01-01

    Several models in rat liver have been developed to study multistage carcinogenesis, including the Solt-Farber resistant hepatocyte model. In this model, initiation consists of either a necrogenic dose of a hepatocarcinogen or a non-necrogenic dose in conjunction with partial hepatectomy (PH). As an alternative to PH, we investigated two different procedures: fasting for 96 h followed by refeeding, or the use of one-day-old neonates. Male Fisher 344 rats were injected p.o. with diethylnitrosamine (DEN) (0, 20, or 100 mg/kg) 24 h after refeeding or PH (controls received DEN alone with no proliferative stimulus). For the neonatal group, male and female Fisher 344 rats were treated with DEN (0 or 20 mg/kg, i.p.) at one day of age. All initiated animals were treated at the same age (11 weeks) with the following selection agents: three daily doses of 2-acetylaminofluorene (AAF) (30 mg/kg), followed by a single dose of carbon tetrachloride (2 ml/kg), followed by three additional daily treatments of AAF (30 mg/kg). Rats were euthanized 2 weeks after the last AAF injection. The PH, neonatal male, and neonatal female groups receiving DEN developed more γ-glutamyl transpeptidase (GGT)-positive foci per cubic centimeter and foci per liver as compared to untreated rats receiving the same proliferative stimulus, whereas the fasting/refeeding group and the group receiving no proliferative stimulus did not. All DEN-treated groups receiving one of the proliferative stimuli had more foci per cubic centimeter than the DEN-treated group receiving no proliferative stimulus. The volume fractions of GGT-positive foci in the PH/DEN and neonatal male/DEN groups were higher than those of both the DEN-treated group receiving no proliferative stimulus and the groups receiving the same proliferative stimulus without DEN. In neonatal females-receiving DEN, the volume fraction was not different from either neonatal females not receiving DEN or DEN-treated rats receiving no proliferative

  6. Effect of ursodeoxycholic acid on bile secretion after endoscopic nasobiliary drainage in patients with cholestatic liver disease of various causes

    Directory of Open Access Journals (Sweden)

    LI Lei

    2016-03-01

    Full Text Available ObjectiveTo observe the effect of ursodeoxycholic acid (UDCA on bile secretion in patients with cholestatic liver disease of various causes. MethodsA total of 48 patients who underwent endoscopic nasobiliary drainage (ENBD in Beijing You′an Hospital Affiliated to Capital Medical University from July 2013 to May 2014 were enrolled and divided into UDCA treatment group (n=36 and control group (n=12. The patients in the UDCA group were further divided into common bile duct stone group (n=9, cholangiocarcinoma group (n=7, sclerosing cholangitis group (n=7, and post-liver transplantation group (n=13. The patients in the UDCA treatment group received oral UDCA capsules (250 mg, 3 times/day since the second day after surgery, and the daily volume of bile drainage was recorded for 7 days after surgery. Serum levels of total bilirubin (TBil, total bile acid (TBA, gamma-glutamyl transpeptidase (GGT, and alkaline phosphatase (ALP were measured on the day before surgery and the 7th day after surgery, and the effects of UDCA on volume of bile drainage, TBil, TBA, GGT, and ALP were compared between groups. The t-test was applied for comparison between groups, comparison of continuous data between these groups was made by analysis of variance; the chi-square test was applied for comparison of categorical data between groups. ResultsCompared with the control group, the UDCA treatment group had a significantly increased volume of bile drainage on the 3rd, 4th, and 5th days after surgery (t=2.461, 3.896, and 2.760; P=0.048, 0.021, and 0.034, and the increase in volume of bile drainage was more significant in the common bile duct stone group, the cholangiocarcinoma group, and the post-liver transplantation group, with peak values appearing on the 4th day after surgery. The patients in the common bile duct stone group and the post-liver transplantation group had significantly lower serum levels of TBil, GGT, and ALP on the 7th day after surgery (t=3.340, 2

  7. Cytologic alterations in the oral mucosa after chronic exposure to ethanol Alterações citológicas na mucosa bucal após exposição crônica ao etanol

    Directory of Open Access Journals (Sweden)

    Sílvia Regina de Almeida Reis

    2006-04-01

    Full Text Available The effects of ethanol alone on the oral mucosa are still poorly understood, especially because there are few non-smoking chronic consumers of alcoholic beverages. The aim of this study was to evaluate the frequency of micronucleus, abnormal nucleus/cytoplasm ratio, pyknosis, karyorrhexis and karyolysis in exfoliated cells from the buccal mucosa and from the lateral border of the tongue in 36 non-smoker alcoholics (ethanol group and 18 non-smokers and non-drinkers (control group. The Papanicolaou method was used. Since alcoholics generally have hepatobiliary involvement, the association between serum gamma-glutamyl transpeptidase (GGT and some of the analyzed oral mucosa alterations was also investigated. The ethanol group showed a significant increase in the frequency of all alterations analyzed in the tongue cells when compared with the control group (p 0.05; Mann-Whitney. In the ethanol group, the correlation between serum GGT and the frequency of micronucleus and abnormal nucleus/cytoplasm ratio in oral mucosa cells was not significant (p > 0.05; Spearman. In conclusion, chronic exposure to ethanol may be associated with carcinogenic cytologic changes in the oral mucosa, even in the absence of tobacco smoking. These alterations were not correlated with hepatobiliary injury.Os efeitos do etanol isoladamente sobre a mucosa bucal permanecem pouco esclarecidos, sobretudo devido ao baixo número de não-fumantes consumidores crônicos de bebidas alcoólicas. O objetivo deste estudo foi avaliar as freqüências de micronúcleo, relação núcleo/citoplasma anormal, picnose, cariorrexe e cariólise em células esfoliadas da mucosa jugal e do bordo lateral da língua de 36 alcoólatras não-fumantes (grupo etanol e 18 abstêmios de álcool e fumo (grupo controle. O método de Papanicolaou foi utilizado. Uma vez que indivíduos alcoólatras geralmente apresentam comprometimento hepatobiliar, a associação entre gama-glutamil transpeptidase (GGT s

  8. Hepatobiliary scintigraphy for early diagnosis of biliary atresia

    DEFF Research Database (Denmark)

    Brittain, Jane Maestri; Kvist, Nina; Johansen, Lars Søndergaard

    2016-01-01

    -glutamyl transpeptidase (GGTP) than non-BA patients with non-draining HS (p = 0.019) or draining HS (p = 0.0001). CONCLUSIONS: HS plays an important role in the diagnostic strategy of infantile jaundice due to conjugated hyperbilirubinaemia. It is a non-invasive method that only seldomly calls for sedation. A high...

  9. Case report

    African Journals Online (AJOL)

    SA); C W N Spearman, FCP (SA), PhD. Division of Hepatology ... elevated alanine aminotransferase and gamma-glutamyl transpeptidase levels for up to 18 months. Risk factors include female gender (2:1), age >55 years and duration of.

  10. measurements of iron status and survival in african iron overload

    African Journals Online (AJOL)

    Serum concentrations of lactate dehydrogenase (LDH), AST, alanine aminotransferase (ALT), garnma-glutamyl transpeptidase. (-yGT), bilirubin, glucose and sodi~ were measured using an automated clinical chemistry analyser. Erythrocyte sedimentation rate (ESR) was determined using the Westergren method. C-reactive ...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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) (p6.85pg/mg albumin) had significantly elevated level of total bilirubin (pMalaysia. 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 order to assess aflatoxin exposure in the general population of Malaysia. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. Associations between Urinary Excretion of Cadmium and Renal Biomarkers in Nonsmoking Females: A Cross-Sectional Study in Rural Areas of South China

    Directory of Open Access Journals (Sweden)

    Yun-rui Zhang

    2015-09-01

    Full Text Available Objectives: The aim of this study was to systematically evaluate the relationship between urinary excretion of cadmium (U-Cd and biomarkers of renal dysfunction. Methods: One hundred eighty five non-smoking female farmers (aged from 44 to 71 years were recruited from two rural areas with different cadmium levels of exposure in southern China. Morning spot urine samples were collected for detecting U-Cd, urinary creatinine (U-cre, β2-microglobulin (β2-MG, α1-microglobulin (α1-MG, metallothionein (MT, retinol binding protein (RBP, albumin (AB, N-acetyl-β-D-glucosaminidase (NAG, alkaline phosphatase (ALP, γ-glutamyl transpeptidase (GGT and kidney injury molecule-1 (KIM-1. Spearman’s rank correlation was carried out to assess pairwise bivariate associations between continuous variables. Three different models of multiple linear regression (the cre-corrected, un-corrected and cre-adjusted model were used to model the dose-response relationships between U-Cd and nine urine markers. Results: Spearman’s rank correlation showed that NAG, ALP, RBP, β2-MG and MT were significantly associated with U-Cd for both cre-corrected and observed data. Generally, NAG correlated best with U-Cd among the nine biomarkers studied, followed by ALP and MT. In the un-corrected model and cre-adjusted model, the regression coefficients and R2 of nine biomarkers were larger than the corresponding values in the cre-corrected model, indicating that the use of observed data was better for investigating the relationship between biomarkers and U-Cd than cre-corrected data. Conclusions: Our results suggest that NAG, MT and ALP in urine were better biomarkers for long-term environmental cadmium exposure assessment among the nine biomarkers studied. Further, data without normalization with creatinine show better relationships between cadmium exposure and renal dysfunction.

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

    Directory of Open Access Journals (Sweden)

    Nicole Tegtmeyer

    Full Text Available 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.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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 value of all 3 indices were significantly higher in patients group as compare with the controls (P model for excluding significant liver fibrosis while FIB-4 with a PPV of 61% showed fair correlation with significant fibrosis. Thus, these two non-invasive models for predicting of liver fibrosis, namely APRI and FIB-4, can be utilized in combination as screening tools in monitoring of CHB patients, especially in resource limiting settings.

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

    Science.gov (United States)

    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.

  18. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity.

    Science.gov (United States)

    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.

  19. CELL DAMAGE, ANTIOXIDANT STATUS, AND CORTISOL LEVELS RELATED TO NUTRITION IN SKI MOUNTAINEERING DURING A TWO-DAY RACE

    Directory of Open Access Journals (Sweden)

    Elena Diaz

    2010-06-01

    Full Text Available 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, ?-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

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

    Science.gov (United States)

    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.

  1. Toxicity of titanium dioxide nanoparticles: Effect of dose and time on biochemical disturbance, oxidative stress and genotoxicity in mice.

    Science.gov (United States)

    Rizk, Maha Z; Ali, Sanaa A; Hamed, Manal A; El-Rigal, Nagy Saba; Aly, Hanan F; Salah, Heba H

    2017-06-01

    The toxic impact of titanium dioxide nanoparticles (TiO 2 NPs) on human health is of prime importance owing to their wide uses in many commercial industries. In the present study, the effect of different doses and exposure time durations of TiO 2 NPs (21nm) inducing oxidative stress, biochemical disturbance, histological alteration and cytogenetic aberration in mice liver and bone marrow was investigated. Different doses of (TiO 2 NPs) (50, 250 and 500mg/kg body weight) were each daily intrapertioneally injected to mice for 7, 14 and 45days. Aspartate and alanine aminotransferases (AST &ALT), gamma glutamyl transpeptidase (GGT), total protein, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) levels were measured. The work was extended to evaluate the liver histopathological pattern and the chromosomal aberration in mice spinal cord bone marrow. The results revealed severe TiO 2 NPs toxicity in a dose and time dependent manner with positive correlation (r=0.98) for most investigated biochemical parameters. The same observation was noticed for the histological analysis. In case of cytogenetic study, chromosomal aberrations were demonstrated after injection of TiO 2 NPs with 500mg/kg b. wt. for 45days. In conclusion, the selected biochemical parameters and the liver architectures were influenced with dose and time of TiO 2 NPs toxicity, while the genetic disturbance started at the high dose of exposure and for long duration. Further studies are needed to fulfil the effect of TiO 2 NPs on pharmaceutical and nutritional applications. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. 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.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  4. Clinical efficacy of puerarin combined with compound ammonium glycyrrhetate S in treatment of alcoholic hepatitis

    Directory of Open Access Journals (Sweden)

    JI Huichun

    2014-10-01

    Full Text Available ObjectiveTo investigate the clinical efficacy of puerarin combined with compound ammonium glycyrrhetate S in the treatment of alcoholic hepatitis. MethodsA total of 92 patients with alcoholic hepatitis who were admitted to our hospital from February 2011 to February 2014 were recruited in this study and randomly divided into two groups. The control group (n=46 was treated with conventional therapy combined with compound ammonium glycyrrhetate S. The test group (n=46 was treated with puerarin in addition to the regimen used in the control group. After 20 days of treatment, the levels of total bilirubin (TBil, alanine aminotransferase (ALT, aspartate aminotransferase (AST, glutamyl transpeptidase (GGT, albumin (Alb, Glasgow alcoholic hepatitis score (GAHS, and abdominal ultrasound were measured and compared with the results before the treatment in both groups. The clinical efficacy and adverse reactions in the two groups were also compared. ResultsAfter the treatment, the GAHSs and levels of TBil, ALT, AST, and GGT in the two groups were all significantly lower than those before the treatment (all P<0.05. In the test group after the treatment, the levels of TBil (20.96±6.85 μmol/L, ALT (33.72±14.18 U/L, and AST (38.69±6.38 U/L were all significantly lower than those in the control group (all P<0.05. The marked response rate, overall response rate, and rate of improvement in abdominal ultrasound in the test group were 63.04%, 93.48%, and 44.44%, respectively, all significantly higher than those in the control group (all P<0.05. There was no significant difference in adverse reactions between the two groups (P>0.05. ConclusionFor patients with alcoholic hepatitis, the combined therapy with puerarin and compound ammonium glycyrrhetate S can improve the treatment outcome and protect the liver function, and it has high safety and holds promise for clinical application.

  5. 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).

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Rakesh Shrivastava

    2013-01-01

    Full Text Available Context: 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. Aim: 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. Settings and Design: A cross-sectional study carried out at a tertiary care center. Subjects and Methods: 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. Statistical Analysis Used: Medcalc online software and by Microsoft Excel Worksheet. Chi-square test was used for significance. P value < 0.05 was taken as significant. Results: 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. Conclusions: Out of the three indices, APRI index with a NPV of 95% appeared to be a better model

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  10. Clinical characteristics, etiology, and prognosis of hypoxic hepatitis: an analysis of 68 cases

    Directory of Open Access Journals (Sweden)

    FAN Hebin

    2014-11-01

    Full Text Available ObjectiveTo investigate the clinical characteristics, etiology, and prognosis of hypoxic hepatitis (HH. MethodsThe medical records of 68 patients with HH admitted to our hospital from January 2002 to December 2012 were collected and reviewed. The common causes of HH were analyzed. The patients were divided into groups of survival and death according to the clinical outcomes. The age, sex, and the Sequential Organ Failure Assessment (SOFA score on admission were compared between groups. The clinical and laboratory data, including bilirubin (Bil, alkaline (ALP, gamma-glutamyl transpeptidase (GGT, international normalized ratio (INR, lactate dehydrogenase (LDH, alanine aminotransferase (ALT, and blood urea nitrogen (BUN, were monitored, and the peak of each parameter was compared between groups. Normally distributed continuous data were compared between the two groups using Student′s t-test, and non-normally distributed continuous data were compared using rank sum test. ResultsThe common causes of HH included heart failure (acute myocardial infarction and congestive heart failure, respiratory failure, septic shock, heat shock, and severe allergic reactions to bee sting. Sharply increasing levels of serum ALT and AST were observed in all patients. The 28-day in-hospital mortality rate was 33.8%. Significant differences between two groups were observed in age of admission (P<0.001, SOFA value (P<0.001, and peak levels of Bil (P<0.001, ALP (P<0.001, GGT (P= 0.001, INR (P<0.001, LDH (P<0.001, ALT (P=0.013, and BUN (P<0.001. The treatments of HH mainly targeted the primary disease, while adjuvant therapies such as nutritional support and liver protection were also needed. ConclusionThe prognosis of HH is poor and the mortality rate is high. The major cause of death is cardiogenic shock, followed by septic shock and acute myocardial infarction. Protecting vital organs from injury and preventing infection play important roles in improving

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  13. 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

    Directory of Open Access Journals (Sweden)

    Haafiz A

    2011-04-01

    -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 analysis for alanine aminotransferase, TB, and GGT combination (L-CTGF, 0.16; P = 0.5; P-CTGF —0.3; P = 0.2 as well as WBC, platelet count, and TB (L-CTGF: —0.36; P = 0.09; P-CTGF —0.33; P = 0.13 also revealed nonsignificant results.Conclusion: Hepatic expression of fibrogenic markers can be correlated with routinely performed blood tests in patients with BA. We document that although a trend of inverse relationship is noted, hepatic CTGF expression does not correlate well with routinely performed blood tests in advanced BA. Further work is required to determine more reliable ways of noninvasive diagnosis of HF.Keyword: connective tissue growth factor, liver fibrosis, blood tests, fibrogenesis

  14. 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.

    Science.gov (United States)

    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

  15. Is gamma glutamyl transferase a diagnostic marker of prostate ...

    African Journals Online (AJOL)

    McRoy

    2013-08-05

    Aug 5, 2013 ... INTRODUCTION. Prostate cancer is the commonest cancer among Nigerian males and the specific cause remains unknown.[1] Risk factors for prostate cancer include age, genetics, race, diet, lifestyle, nationality, family history, infection and inflammation of the prostate and other factors.[2]. Benign prostatic.

  16. Anti-inflammatory effects and hepatotoxicity of Tripterygium-loaded solid lipid nanoparticles on adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Xue, Mei; Jiang, Zhen-zhou; Wu, Tao; Li, Ji; Zhang, Liang; Zhao, Yan; Li, Xue-jun; Zhang, Lu-Yong; Yang, Shu-yu

    2012-08-15

    Tripterygium wilfordii Hook f. (TWHF) has been demonstrated to have anti-inflammatory, immunosuppressive effects and its clinical use was restricted to some extent due to some toxic effects on the digestive, urogenital, and blood circulatory systems, especially the male reproductive system. In the previous study, we had confirmed that TWHF-loaded solid lipid nanoparticles (SLN) have protective effects on male reproductive toxicity in rats. Anti-inflammatory effects and hepatotoxicity of TWHF-SLN remain to be unidentified. The present study was focused on the anti-inflammatory effect of complete Freund's adjuvant-induced arthritis in rats treated with TWHF-SLN as well as the effects of SLN delivery system on decreasing the hepatotoxicity induced by tripterygium. Sixty-four healthy male rats were randomly divided into eight groups with eight rats each. From day 18 after FCA injection, TWHF-SLN group (120, 60, 30 mg/kg) and TWHF group (120, 60, 30 mg/kg) were administered by oral gavage for 24 consecutive days. The control group was with saline and model control group was without any treatment. The volume of the right hind paws was evaluated at 0, 4, 8, 12, 18, 24, 30, 36 and 42 days post-injection of FCA by a home-made connected device. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL) and albumin (ALB) levels were evaluated by an autoanalyzer. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) malondialdehyde (MDA) and xanthine oxidase (XOD) levels were determined using commercial kits. The PG level in sera was examined by double antibody sandwich method. Tissue histopathology was evaluated with hematoxylin and eosin (H&E). The results show that TWHF-SLN can significantly reduce rat paw volume at 60 mg/kg (psystem can enhance the anti-inflammatory activity of TWHF, and meanwhile has a protective effect against TWHF

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

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Shipra; Shukla, Yogeshwer; Paul, Bhola N; Chowdhuri, D Kar; Khanna, Subhash K [Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box 80, Lucknow-226001 (India); Das, Mukul [Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box 80, Lucknow-226001 (India)

    2007-11-01

    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. The 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

  18. Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate

    Directory of Open Access Journals (Sweden)

    Janh Carlo de Amorim Ferreira

    2015-06-01

    Full Text Available ABSTRACT. Ferreira J.C.A., Botelho G.G. & Acceta J.L. [Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate.] Perfil hepático de gatos domésticos anestesiados com Propofol em infusão contínua. Revista Brasileira de Medicina Veterinária, 37(2:127-132, 2015. Curso de Medicina Veterinária, Departamento de Medicina e Cirurgia Veterinária, Universidade Federal Rural do Rio de Janeiro, BR 465 Km 7, Seropédica, RJ 23890-000, Brasil. E-mail: janhcarlo@yahoo.com.br This study was performed to evaluate the hepatic biochemical profile of cats when submitted to continuous infusion of propofol at a 0,3 mg/kg/min in dosage, for 90 minutes, and comparing to the results obtained from cats receiving continuous infusion of saline solution. Both groups were analyzed during a pre-determined period of time totalizing 12 hours of observation and analysis. The following enzymes activity levels were determined: Aspartate-Aminotransferase (AST, Alanina-Aminotransferase (ALT, Gamma Glutamyl Transpeptidase (GGT and Alkaline Phosphatase (AP; serum levels of Albumin (A, Total Bilirrubin (BT and Total Serum Proteins (sTP. Twenty healthy cats were analyzed on this study, their weights varying from two to four kg and ages between three to five years old, submitted to experimental procedures performed during the months of January and February, 2010. The analysis of these results showed a major difference (p<0,05 between the ALT serum activities at the following moments: T2 (30 minutes, T3 (60 minutes, and T5 (12 hours; AST and AP serum activities at T2. None of the animals presented averages of the results above parameters of normality. The other parameters examined did not present any significant differences, concluding that total intravenous anesthesia using continuous infusion of propofol was safe to hold cats for invasive surgical procedures, therefore providing more information regarding the safe use of this drug in this species.

  19. Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate

    Directory of Open Access Journals (Sweden)

    Janh Carlo de Amorim Ferreira

    2014-06-01

    Full Text Available ABSTRACT. Ferreira J.C.A., Botelho G.G. & Accetta J.L. [Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate.] Perfil hepático de gatos domésticos anestesiados com propofol em infusão contínua. Revista Brasileira de Medicina Veterinária, 36(2:116-120, 2014. Cirurgia e Anatomia Topográfica, UNIPLI/Anhanguera, Rua Visconde do Rio Branco, 137, Centro, Niterói, RJ 24020-001, Brasil. E-mail: janhcarlo@yahoo.com.br This study was performed to monitor the hepatic biochemical profile of cats when submitted to continuous infusion of propofol at a 0.3 mg/kg/min dosage, for 90 minutes, and comparing to results obtained from cats who received continuous infusion of saline solution. Both groups were analyzed during a pre-determined period of time totalizing 12 hours of observation and analysis. The following enzymes activity levels were determined: Aspartate-Aminotransferase (AST, Alanina-Aminotransferase (ALT, Gamma Glutamyl Transpeptidase (GGT and Alkaline Fosfatasis (FA; serum levels of Albumin (A, Total Bilirrubin (BT and Total Serum Proteins (PT. Twenty healthy cats were analyzed on this study, their weights varying from two to four kg and ages between three to five years old, submitted to experimental procedures performed during the months of January and February, 2010. The analysis of these results showed a major difference (p<0.05 between the ALT serum activities at the following moments: T2 (30 minutes, T3 (60 minutes, and T5 (12 hours; AST and FA serum activities at T2. None of the animals presented averages of the results above parameters of normality. The other parameters examined did not present any significant differences, concluding that total intravenous anesthesia using continuous infusion of propofol was safe to hold cats for invasive surgical procedures, therefore providing more information regarding the safe use of this drug in this species.

  20. Protective Role of Carnitine against the Harmful Biological Effects of Paracetamol and Radiation Exposure in Male Albino Rats

    International Nuclear Information System (INIS)

    Abd El Rahman, N.A.

    2012-01-01

    L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain fatty acids to produce energy. Furthermore it has been shown to protect cells from per oxidative stress. The objective of the present study was to evaluate the efficacy of L-carnitine on hepatotoxicity and nephrotoxicity induced by paracetamol, γ-radiation, and paracetamol + γ-radiation. Male albino rats were divided into 8 groups. 1-Control group: rats not subject to any treatment, 2-Carnitine group: rats received L-carnitine (0.5 ml/Kg body weight) via intraperitoneal injection during 21 days, 3-Paracetamol group: rats received paracetamol (50 mg/kg body) via intraperi-toneal injection during 21 days, 4- Carnitine + Paracetamol group: rats received L-carnitine in parallel to paracetamol treatment, 5- Radiation groups: rats were whole body gamma irradiated with 7 Gy, 6- Carnitine + Radiation group: rats received L-carnitine for 21 days before whole body gamma irradiation with 7Gy, 7- Paracetamol + Radiation group: rats received paracetamol during 21 days before whole body gamma irradiation, 8- Carnitine + Paracetamol + Radiation group: rats received L-carnitine parallel to paracetamol during 21 days before whole body gamma irradiation.The results demonstrated that rats receiving paracetamol, as well as whole body gamma irradiated rats and rats receiving paracetamol and irradiated showed a significant increase of alanine amino transferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP) activities, and a significant decrease of gamma-glutamyl transpeptidase (GGT) activity indicating liver injury. A significant increase of urea, creatinine and uric acid levels was recorded also indicating kidney damage. Alteration in liver and kidney functions was accompanied by a significant increase in the content of thiobarbituric acid reactive substances (TBARS) associated with a significant decrease in glutathione (GSH) content and superoxide

  1. Independent predictive factors for significant liver histological changes in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal alanine aminotransferase level

    Directory of Open Access Journals (Sweden)

    LI Qiang

    2016-07-01

    Full Text Available Objective To investigate the independent predictive factors for significant liver histological changes (SLHCs in patients with HBeAg-positive high-viral-load chronic hepatitis B virus (HBV infection and a normal alanine aminotransferase (ALT level. MethodsA retrospective analysis was performed on the clinical data of 116 previously untreated patients with HBeAg-positive high-viral-load (HBV DNA≥105 copies/ml chronic HBV infection and a normal ALT level (<50 U/L who were hospitalized in Shanghai Public Health Clinical Center Affiliated to Fudan University from June 2013 to August 2015. The definition of SLHCs was inflammation ≥G2 and/or fibrosis≥S2. The t-test or Mann-Whitney U rank sum test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate regression analyses were used to determine independent predictive factors for SLHCs. ResultsOf all the 116 patients, 47(40.5% had SLHCs. The multivariate analysis showed that age (OR=2.828, P<0.05, ALT (OR=1.011, P<0.05, and gamma-glutamyl transpeptidase (GGT (OR=1.089, P<0.05 were independent predictors for SLHCs in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level. The patients aged ≤30 years had a significantly lower incidence rate of SLHCs than those aged>30 years (21.6% vs 49.4%, χ2=6.42, P=0.015, the patients with ALT ≤30 U/L had a significantly lower incidence rate of SLHCs than those with 30 U/L<ALT≤50 U/L (17.6% vs 50.0%, χ2=19.86, P<0.001, and the patients with GGT≤40 U/L had a significantly lower incidence rate of SLHCs than those with GGT>40 U/L (28.8% vs 66.7%, χ2=28.63, P<0.001. ConclusionIn patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level, those with an age of>30 years, ALT>30 U/L, and GGT>40 U/L tend to develop SLHCs and need liver biopsy.

  2. Comparison of gamma glutamyltransferase in normal and in type 2 diabetics

    International Nuclear Information System (INIS)

    Iqbal, A.

    2010-01-01

    Objective: Comparison of gamma glutamyltransferase in normal and type 2 diabetics. Methods: In a cross-sectional study, 100 apparently normal healthy subjects and, 47 type 2 diabetic subjects were selected from either sex with ages between 18-65 years. Subjects were measured for waist/hip ratio, BMI and serum levels of ALT, AST, Alk Phosphatase and Glutamyl Transferase (GGT). The study excluded by screening for Anti HCV, HBsAg and patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), GGT levels more than three times the normal and subject with a total leukocyte count more than 10,000/ mu l. Results: The levels of GGT levels were found to be most significant among all the liver enzymes (P = 0.001). The levels of GGT compared with type 2 diabetics was found to be significantly increased when compared with BMI, waist/circumference, cholesterol, triglycerides (TG), High Density Lipoprotein (HDL), Low density Lipoprotein (LDL), fasting blood sugar level and blood pressure (P = 0.001). The pearson regression analysis showed a positive relation with systolic, diastolic blood pressure and fasting blood sugar. Conclusion: These results indicate that levels of GGT were raised with increased waist girth, BMI, blood pressure TG and low HDL, all of these are the features of metabolic syndrome according to ATP III criteria. Hence, serum GGT may be an important investigation for diabetes and metabolic syndrome. (author)

  3. Clinical efficacy of Qinggan Huashi Huoxue decoction combined with liver-protecting and enzyme-lowering drugs in treatment of alcoholic liver disease

    Directory of Open Access Journals (Sweden)

    YAO Zhishan

    2016-07-01

    Full Text Available ObjectiveTo investigate the clinical efficacy and safety of Qinggan Huashi Huoxue decoction combined with liver-protecting and enzyme-lowering drugs in the treatment of alcoholic liver disease (ALD. MethodsA total of 175 ALD patients who were admitted to The Second People′s Hospital of Tangshan from January 2012 to December 2015 were enrolled and randomly divided into treatment group (87 patients and control group (88 patients. The patients in the control group were asked to quit smoking and were given nutritional support and medications including polyene phosphatidylcholine, reduced glutathione, magnesium isoglycyrrhizinate, and ursodeoxycholic acid capsules, and those in the treatment group were given the self-made traditional Chinese medicine Qinggan Huashi Huoxue decoction in addition to the therapeutic regimen for the control group. During the three courses of treatment (12 weeks, the patients′ clinical symptoms and signs were observed, liver function [alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyl transpeptidase (GGT, albumin (Alb, and total bilirubin (TBil] and blood lipids [total cholesterol (TC, triglyceride (TG, high-density lipoprotein (HDL, and low-density lipoprotein (LDL] were performed regularly, the results of routine blood tests and abdominal ultrasound findings were recorded regularly, and adverse events which occurred during treatment were recorded. The independent samples t-test was used for comparison of continuous data between groups, an analysis of variance with repeated measures was used to compare the differences at each time point between the two groups, and the chi-square test was used for comparison of categorical data between groups. ResultsAfter treatment, all patients achieved varying degrees of improvements in clinical symptoms and signs, which showed significant differences between the two groups at weeks 4, 8, and 12 of treatment (t=14.390, 10.487, and 13.547, all P

  4. Clinical effect of Mongolian medicine Qinggan Jiuwei powder in treatment of alcoholic liver fibrosis

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    GE Hongyan

    2017-12-01

    Full Text Available ObjectiveTo observe the clinical effect of Mongolian medicine Qinggan Jiuwei powder in the treatment of alcoholic liver fibrosis by observing the improvement in imaging indices. MethodsA total of 104 patients with alcoholic liver fibrosis who visited Department of Gastroenterology in Horqin District First People′s Hospital in Tongliao from October 2015 to January 2017 were enrolled and randomly divided into experimental group and control group, with 52 patients in each group. The patients in the experimental group were given Mongolian medicine Qinggan Jiuwei powder, while those in the control group were given reduced glutathione tablets. Liver function parameters, liver-spleen ultrasound findings, and liver stiffness measurement (LSM determined by FibroScan were observed before and after treatment. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the paired samples t-test was used for comparison within each group; the Wilcoxon rank sum test was used for comparison of non-normally distributed continuous data between groups. ResultsBoth groups had varying degrees of improvements in clinical symptoms and signs. Both groups had significant changes in alanine aminotransferase, aspartate aminotransferase (AST, gamma-glutamyl transpeptidase (GGT, and LSM after treatment (experimental group: Z=-3.09, -7.19, and -8.27, t=7.13, P=0.002, <0.001, <0.001, and <0.001; control group: Z=-3.28, -4.60, and -5.06, t=8.54. P=0.001, <0.001, <0.001, and <0.001. There were significant differences in AST and GGT after treatment between the two groups (Z=-2.02 and -2.15, P=0.04 and 0.03. Both groups had significant changes in oblique diameter of the right liver lobe, diameter of the portal vein, blood flow rate of the portal vein, spleen thickness, and diameter of the splenic vein after treatment (experimental group: t=6.48,11.02,2.20,3.30 and 5.30, P<0.001, <0.001, =0.030, <0

  5. 14C leucine chloromethylketone interaction with sarcoma 37 cell plasma membrane components

    International Nuclear Information System (INIS)

    Matthews, R.H.; Milo, G.E.; McMichael, T.L.; Lewis, N.J.

    1982-01-01

    Leucine chloromethylketone labelling of viable S37 cells was preferential for the plasma membrane fraction. The pattern of radiolabelling of the plasma membrane proteins was time-dependent. After 5 min the radiolabel was localized with glutamyl transpeptidase, and subsequently, with other physiologically active proteins as a function of time after incubation. Labelling of proteins was temperature-dependent and incubation of viable S37 cells with the radiolabelled substrate at 0 0 C yielded little or no radioactivity localized in the plasma membrane. The molecular weight of one radiolabelled substratemembrane protein complex was estimated on sodium dodecyl sulfate polyacrylamide gel electrophoresis to be between 100,000-200,000. (author)

  6. Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Gronbaek, M.; Tybjaerg-Hansen, A.

    2009-01-01

    the Copenhagen City Heart Study. Biochemical tests for the detection of liver damage were specific for alanine aminotransferase (ALT), aspartate aminotransferase (AST)-to-ALT ratio (AST/ALT), gamma-glutamyl transpeptidase (gamma-GT), albumin, bilirubin, alkaline phosphatase, coagulation factors, and erythrocyte...... volume. RESULTS: Increasing alcohol intake was associated with increasing erythrocyte volume, AST/ALT, and levels of ALT, gamma-GT, albumin, bilirubin, coagulation factors, and with decreasing levels of alkaline phosphatase. Multifactorially adjusted hazard ratios for alcoholic liver disease overall were...

  7. An evaluation of the Olympus "Quickrate" analyser.

    Science.gov (United States)

    Williams, D G; Wood, R J; Worth, H G

    1979-02-01

    The Olympus "Quickrate", a photometer built for both kinetic and end point analysis was evaluated in this laboratory. Aspartate transaminase, lactate dehydrogenase, hydroxybutyrate dehydrogenase, creatine kinase, alkaline phosphatase and gamma glutamyl transpeptidase were measured in the kinetic mode and glucose, urea, total protein, albumin, bilirubin, calcium and iron in the end point mode. Overall, good correlation was observed with routine methodologies and the precision of the methods was acceptable. An electrical evaluation was also performed. In our hands, the instrument proved to be simple to use and gave no trouble. It should prove useful for paediatric and emergency work, and as a back up for other analysers.

  8. Endoscopic ultrasound-guided radiofrequency ablation of the pancreas

    DEFF Research Database (Denmark)

    Silviu, Ungureanu Bogdan; Daniel, Pirici; Claudiu, Mărgăritescu

    2015-01-01

    ultrasound (EUS)-guided radiofrequency ablation (RFA) probe through a 19G needle in order to achieve a desirable necrosis area in the pancreas. Radiofrequency ablation of the head of the pancreas was performed on 10 Yorkshire pigs with a weight between 25 kg and 35 kg and a length of 40-70 cm. Using an EUS...... analysis revealed increased values of amylase, alkaline phosphatase, and gamma-glutamyl transpeptidase on the 3rd day but a decrease on the 5th day. After necropsy and isolation of the pancreas, the ablated area was easily found, describing a solid necrosis. The pathological examination revealed...

  9. Transporting Capacity of Albumin in Patients with Severe Mechanical Injury During Intravascular Laser Irradiation

    Directory of Open Access Journals (Sweden)

    V. V. Moroz

    2005-01-01

    Full Text Available The changes in the parameters of the transporting capacity of albumin, in some biochemical plasma parameters, and in the impact of low-energy laser irradiation on the studied parameters were examined in patients with severe mechanical injury in the early posttraumatic period. Thirty patients aged 17 to 70 years who had a health status of 78 to 98 scores by the APACHE-III scale were examined. The results indicated that as a consequence of prior hypoxia of mixed genesis and subsequent reperfusion and later on due to the development of endogenous intoxication, there were changes in the transporting capacity of albumin and in the de Ritis coefficient, a reduction in cholesterol concentrations, and increases in the levels of triglycerides and in the activity of gamma-glutamyl transpeptidase. Early quantum hemotherapy as a part of complex treatment makes it possible to prevent the progressive deterioration of the transporting capacity of plasma albumin, the critical reduction in the effective concentration of albumin, contributes to a more rapid recovery of the lowered levels of cholesterol and to a further increase in the activity of gamma-glutamyl transpeptidase, which is indicative of the recovered biosynthetic activity of the liver and its enhanced detoxifying activity.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. RELATIONSHIP BETWEEN SOME BIOCHEMICAL PARAMETERS IN HEALTHY AND DAIRY COWS WITH SUBCLINICAL KETOSIS

    Directory of Open Access Journals (Sweden)

    Gülşah Akgül

    2017-07-01

    Full Text Available The aim of the presented study is to compare beta-hydroxy butyric acid (BHBA, glucose (GLU gamma-glutamyl transferase (GGT, phosphorus (P, calcium (Ca, and albumin (Alb values of healthy animals and animals suffering from subclinical ketosis. The material in this study consisted of 15 healthy cows and 15 cows with subclinical ketosis on a commercial dairy farm located in Bursa (Turkey. Significant differences (p<0.001 were observed in BHBA, GLU, and Ca between the two groups. Results of this study might indicate the importance of calcium metabolism in the pathogenesis of the disease.

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

    Science.gov (United States)

    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.

  15. Staphylococcus aureus HemX Modulates Glutamyl-tRNA Reductase Abundance To Regulate Heme Biosynthesis

    OpenAIRE

    Jacob E. Choby; Caroline M. Grunenwald; Arianna I. Celis; Svetlana Y. Gerdes; Jennifer L. DuBois; Eric P. Skaar; Kimberly A. Kline

    2018-01-01

    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 hom...

  16. Bacillus lichenformis γ-glutamyl exopolymer: Physicochemical characterization and U(VI) interaction

    International Nuclear Information System (INIS)

    He, L.M.; Neu, M.P.; Vanderberg, L.A.

    2000-01-01

    Complexation by microbially produced exopolymers may significantly impact the environmental mobility and toxicity of metals. This study focused on the conformational structure of the bacterial exopolymer, γ-D-poly(glutamic acid) and its interactions with U(VI) examined using ATR-FTIR spectroscopy. Solution pH, polymer concentration, and ionic strength affected the conformation of the exopolymer, and U(VI) binding was monitored. At low pH, low concentration, or low ionic strength, this exopolymer exists in an α-helical conformation, while at high pH, concentration, or ionic strength the exopolymer exhibits a β-sheet structure. The change in exopolymer conformation is likely to influence the number and nature of exposed surface functional groups, sites most responsible for metal complexation. The authors found the polyglutamate capsule binds U(VI) in a binuclear, bidentate fashion; in contrast the glutamate monomer forms a mononuclear, bidentate complex with U(VI). The apparent polynuclear binding of U(VI) may induce β-sheet structure formation provided the U(VI) Concentration is sufficiently high

  17. γ-Glutamyl semialdehyde and 2-amino-adipic semialdehyde: biomarkers of oxidative damage to proteins

    DEFF Research Database (Denmark)

    Daneshvar, B.; Frandsen, H.; Autrup, Herman

    1997-01-01

    proteins collected from eight different mammalian species was found to be inversely proportional to their maximum lifespan potential. The content of AAS in plasma proteins of untreated adult rats showed a positive correlation with the age of the rat. In young rats a negative correlation with age was found......Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify...

  18. A futile cycle, formed between two ATP-dependant γ-glutamyl cycle ...

    Indian Academy of Sciences (India)

    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 ...

  19. Passive immunity transfer and serum constituents of crossbred calves

    Directory of Open Access Journals (Sweden)

    Thaís G. Rocha

    2012-06-01

    Full Text Available Passive immunity transfer (PIT evaluation is an essential tool for the maintenance of healthy calves during the first months of life. Since lactation number and breed have been proven to influence immunoglobulin levels in colostrum, the aim of this study was to evaluate PIT from primiparous and multiparous Canchim cows to their calves. Blood samples were collected from the calves before colostrum intake and 1, 2, 7, 15 and 30 days thereafter, while colostrum samples from the cows were taken immediately after parturition. Activities of gamma-glutamyl transferase (GGT, alkaline phosphatase (ALP, and concentrations of total protein, albumin, globulins, immunoglobulin A (IgA, immunoglobulin G (IgG, total and ionized calcium, inorganic phosphorus, magnesium, sodium and potassium were evaluated in calves' serum and activities of GGT and ALP and concentrations of total protein, IgA and IgG were assessed in cow's colostrum whey. Immunoglobulins concentrations were evaluated by electrophoresis in polyacrylamide gels. Serum biochemistry evaluations revealed an increase in gamma-glutamyl transferase and alkaline phosphatase activities and in total protein, globulins, immunoglobulin A and immunoglobulin G levels in calves' serum after colostrum intake. Only total protein and light chain immunoglobulin G levels in colostrum whey were affected by the cows' lactation number. Phosphorus and magnesium levels in blood serum increased after colostrum intake, while sodium and potassium levels oscillated in the experimental period. PIT was influenced by the cows' lactation number but was efficient in both groups.

  20. Aktivitas Antifibrotik Ekstrak Buah Delima Terstandar 40% Ellagic Acid pada Tikus Putih (Rattus norvegicus sebagai Hewan Model (ANTIFIBROTIC ACTIVITY OF POMEGRANATE FRUIT EXTRACT STANDARDIZED 40% ELLAGIC ACID ON RATS (RATTUS NORVEGICUS AS ANIMAL MODEL

    Directory of Open Access Journals (Sweden)

    Wiwik Misaco Yuniarti

    2014-08-01

    Full Text Available The number of patients with chronic liver disease (fibrosis or cirrhosis of the liver is increasing fromtime to time. However, until now there is no therapy that really effective to overcome that disease. Therapyfor liver fibrosis typically use substance that have antioxidant activity, anti-inflammatory or anti fibrotic.Various efforts always done to find alternative therapies for liver fibrosis. One of them is the use ofpotential plants that suspected having such activity. Various parts of pomegranate have been shown tohave various activities that beneficial for health. This study was conducted to determine the effect ofpomegranate fruit extract standardized 40% ellagic acid on the improvement degree of liver fibrosis causedby cholestasis by measuring of serum alkaline phosphatase levels (ALP and gamma-glutamyl transferase(GGT, as a specific indicator of liver damage becaused of cholestasis. The research was conducted by using32 male rats, wistar strain, 2.5 month old, weighing between 150-200 grams. Animal models of liver fibrosis obtained by using BDL technique. Subjects were divided into a control group (P0 = without BDLand giving of pomegranate extract and treatment groups (P1 = BDL with administration of CMC, P2 =BDL with ellagic acid 90% and P3 = BDL with pomegranate fruit extract standardized 40% ellagic acid.CMC, extract (150 mg / kg BW / PO and ellagic acid (60 mg / kg BW / PO administered for 21 consecutivedays in the same volume. At the end of 21 days periods, biochemical evaluation was performed to measureserum levels of GGT and ALP. The result indicated that administration of pomegranate fruit extract ( P3significantly reduced GGT ( 10.5±9.2 mg/dl and ALP level ( 509.0±4.2 mg/dl close to normal level of GGTand ALP ( P0, GGT : 2.8 ± 1.4; ALP : 449.0±62.3 (p<0.05. The level of GGT and ALP in P3 group were lowercompared to the group ellagic acid (P2, GGT=48.5±4.8 and ALP = 691.0± 29.7 and group which only begiven CMC (P1, GGT

  1. Antioxidant activity of eggplant (Solanum melongena) in male albino rats exposed to gamma irradiation

    International Nuclear Information System (INIS)

    Abdel-Magied, N.; Ahmed, A.G.; Abo zid, N.M.

    2012-01-01

    The aim of the study was to evaluate the potential benefits of dietary supplementation of eggplant (Solanum melongena) as antioxidant against γ- rays-induced biochemical changes in male albino rats by estimating some of the components of antioxidant defense in the; liver glutathione content (GSH), superoxide dismutase activity (SOD) and malondialdehyde (MDA), serum aspartate amino transferase,(AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transaminase (GGT), cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol(HDL-C). Male albino rats (120-150 g) were divided into four groups as Control group, group 2 received diet supplemented with 10% of eggplant (Solanum melongnea) fruit for 21 successive days , group 3: irradiated with a single dose (6.5 Gy), group 4 received eggplant for 21 successive days then exposed to 6.5 Gy. All animals were sacrificed after 1, 3 and 8 days post irradiation. Rats exposed to γ-rays exhibited a profound elevation of AST, ALT, ALP and GGT activities, and lipid abnormalities .Noticeable drop in liver GSH content and SOD activity associated with increase of MDA was recorded. Treatment with dietary eggplant for 21 days before irradiation significantly abolished radiation induced elevations in MDA and significantly elevates hepatic GSH content and SOD activity. The levels of cholesterol, TG, HDL-C, LDL-C as well as the activities of AST, ALT, and GGT in serum were significantly ameliorated and noticeable improvement in the lipid profile levels

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

    Science.gov (United States)

    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.

  3. Evaluation of methanolic extract of Phragmites karka on carbon tetrachloride-induced liver fibrosis in rat

    Directory of Open Access Journals (Sweden)

    Atta ur Rehman

    2017-07-01

    Full Text Available Phragmites karka has been reported for its anti-inflammatory and analgesic activities. Here, extracts of leaf and rhizome of the plant were individually investigated in CCl4-induced hepatofibrosis in male Wistar rats by administering CCl4 intraperitoneally biweekly for 6 weeks. Afterwards the animals were investigated for liver fibrosis at biochemical, molecular and histological levels, and it showed a profound increase (p<0.001 in elevation of serum levels of transaminases, γ-glutamyl transpeptidase, mRNA expression of α smooth muscle actin, collagen and transforming growth factor beta (TGFβ, and extracellular matrix deposition and perilobular necrosis. Both extracts markedly (p<0.001 decreased the elevated levels of these markers. Histopathological investigations also substantiated the above results by exhibiting a decreased in extracellular matrix deposition in post-treatment animals. In conclusion, both extracts had substantially modified the biochemical and molecular markers of liver fibrosis, in addition to histological improvement in architecture of liver.

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

    Science.gov (United States)

    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 stress, toxicity and tumour promotion response in rats.

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

    Science.gov (United States)

    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.

  6. Oral cancer.

    Science.gov (United States)

    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.

  7. Effect of parenterally administered cystamine and gammaphos (WR-2721) on some biochemical parameters in dog blood serum

    International Nuclear Information System (INIS)

    Simsa, J.; Tichy, M.; Podzimek, F.; Spelda, S.; Resl, M.; Kuna, P.

    1987-01-01

    The effects were studied of intravenous and intramuscular administration of radioprotectives cystamine and gammaphos in dogs on the biochemical parameters of the blood serum. The activities were studied of enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine kinase, gamma-glutamyl transpeptidase, lactate dehydrogenase, malate dehydrogenase, sorbitol dehydrogenase and alpha-amylase. The contents were determined of total protein, albumin, bilirubin, urea nitrogen, creatinine, glucose, triglycerides, cholesterol, lipids, calcium, sodium and potassium. Cystamine was shown to be hepatotoxic. The intramuscular administration of gammaphos was found to be more advantageous than of cystamine. Only slight increase was observed in the activities of lactate dehydrogenase, malate dehydrogenase, and alpha-amylase. With cystamine, the changes in all biochemical parameters were most marked. (M.D.). 17 figs., 18 refs

  8. Haematinic deficiency and macrocytosis in middle-aged and older adults.

    Directory of Open Access Journals (Sweden)

    Therese McNamee

    Full Text Available 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 21 nmol/ml only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (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. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency.

  9. Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study

    International Nuclear Information System (INIS)

    Mizushima, Takeshi; Ohnishi, Shunsuke; Shimizu, Yuichi; Hatanaka, Yutaka; Hatanaka, Kanako C.; Hosono, Hidetaka; Kubota, Yoshimasa; Natsuizaka, Mitsuteru; Kamiya, Mako; Ono, Shouko; Homma, Akihiro; Kato, Mototsugu; Sakamoto, Naoya; Urano, Yasuteru

    2016-01-01

    Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples. gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured. All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application. Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC

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

    Directory of Open Access Journals (Sweden)

    Takeshi Ogihara

    Full Text Available 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.

  11. [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].

    Science.gov (United States)

    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 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 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 liver biopsy to the certain degree.

  12. Effects of the hepatocarcinogen nafenopin, a peroxisome proliferator, on the activities of rat liver glutathione-requiring enzymes and catalase in comparison to the action of phenobarbital.

    Science.gov (United States)

    Furukawa, K; Numoto, S; Furuya, K; Furukawa, N T; Williams, G M

    1985-10-01

    The biochemical effects in the livers of male rats of prolonged administration of the experimental hepatocarcinogen nafenopin, a hypolipidemic agent and peroxisome proliferator, were compared to those of another experimental liver carcinogen, phenobarbital, which acts as a neoplasm promoter. Feeding of nafenopin, 0.03 mmol/kg basal diet for up to 24 weeks increased the numbers of hepatic peroxisomes, increased catalase activity, markedly decreased cytosolic glutathione transferase activities toward two substrates, decreased cytosolic glutathione peroxidase activities toward H2O2 and two organic peroxides, and suppressed the age-related increase in gamma-glutamyl transpeptidase activity. In contrast the livers of rats fed an equimolar concentration of phenobarbital displayed increases in cytosolic glutathione transferase activities and enhancement of gamma-glutamyl transpeptidase activity but no changes in glutathione peroxidase activities. There was also an enhancement of catalase activity without apparent increase in peroxisome number. Enzyme kinetic analyses revealed that the cytosolic glutathione transferase activities toward two halogenonitrobenzene substrates were inhibited in the rats fed nafenopin and displayed elevated Km and decreased Vmax. Kinetic studies of glutathione transferase activities in which nafenopin was mixed with normal rat liver cytosols in the assay system revealed competitive type inhibition toward 1-chloro-2,4-dinitrobenzene and a noncompetitive type of inhibition toward 3,4-dichloronitrobenzene. Likewise activities of glutathione peroxidases toward H2O2 and cumene hydroperoxide were suppressed by in vitro addition. Thus the effects of nafenopin and phenobarbital on liver biochemistry were very different. The inhibition of hepatic biotransformation and scavenger systems by nafenopin is suggested to be relevant to its hepatocarcinogenicity.

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

    Science.gov (United States)

    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.

  14. 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.

    Directory of Open Access Journals (Sweden)

    Yufeng Gong

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  17. Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

    NARCIS (Netherlands)

    W. Klootwijk (Willem); E. Sleddens-Linkels (Esther); R. de Boer (Renske); C.A. Jansen; R. Autar; W.W. de Herder (Wouter); E.R. Boeve; T.J. Visser (Theo); W.J. de Greef (W.)

    1997-01-01

    textabstractTRH-like peptides have been identified that differ from TRH (pGlu-His- ProNH2) in the middle aminoacid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the

  18. Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

    NARCIS (Netherlands)

    W. Klootwijk (Willem); E. Sleddens-Linkels (Esther); R.D.H. de Boer (Remco); C.A. Jansen; R. Autar; W.W. de Herder (Wouter); E.R. Boeve; T.J. Visser (Theo); W.J. de Greef

    1997-01-01

    textabstractTRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds

  19. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection...... in different types of cancer suggests deregulation of C7orf24 to be a general event in epithelial carcinogenesis, indicating that this protein may play an important role in cancer cell biology and thus constitute a novel therapeutic target. Furthermore, as C7orf24 is externalized to the tissue extracellular...... fluid and can be detected in serum, this protein also represents a potential serological marker....

  20. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection......, and a novel protein, C7orf24, was identified as being upregulated in cancer cells. Protein expression levels of C7orf24 were evaluated by immunohistochemical assays to qualify deregulation of this protein. Analysis of C7orf24 expression showed up-regulation in 36.4 and 23.4% of cases present in the discovery...

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

    Science.gov (United States)

    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.

  2. Effects of high grade bentonite on performance, organ weights and serum biochemistry during aflatoxicosis in broilers

    Directory of Open Access Journals (Sweden)

    H. C. Indresh

    2013-12-01

    Full Text Available Aim: To evaluate the effect of different levels of High Bentonite on growth performance, organ weight and serum biochemistry in broiler fed on diets containing aflatoxin. Materials and Methods: A total of 360 day-old commercial broiler chicks were divided at random into 8 dietary treatment groups of 42 chicks each having 3 replicates. Dietary levels of aflatoxin (0.5 ppm and High-grade bentonite (0.5, 0.75 and 1.00% were tested in a completely randomized design manner, forming a total of 8 dietary treatments each with three replicates. Body weight and feed intake were recorded weekly. At 5 wk, six birds from each treatment were sacrificed and liver, kidney, gizzard, pancreas, spleen, bursa of Fabricius and thymus were extracted and weighed. The serum samples were analyzed for total proteins, uric acid, serum albumin, serum globulin and the activities of gamma glutamyl transferase (GGT, alanine amino transferase (ALT and for antibody titers against Newcastle disease (ND and infectious bursal disease (IBD using ELISA technique. Results: A significant (P<0.05 decrease in body weight, feed consumption, relative weights of bursa, thymus, serum protein, anti body titers against NDV and IBDV, and increase in FCR, mortality, relative weight of liver, kidney, and the activity of Gamma Glutamyl Transferase (GGT was observed. However, the relative weights of gizzard, pancreas, spleen, serum albumin, uric acid and the activity of Alanine Amino Transferase (ALT were not influenced by inclusion of AF or HGB. Conclusion: The addition of HGB restored the harmful effects of AF on body weight, feed consumption, FCR, mortality, relative weight of liver, kidney, serum protein, IBDV and NDV. Supplementation of high grade bentonite at 1.0 per cent level was found to be beneficial in ameliorating the adverse effects of aflatoxin (AF in broiler chickens. [Vet World 2013; 6(6.000: 313-317

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  5. The relationship between 25-hydroxyvitamin D concentration and liver enzymes in overweight or obese adults: Cross-sectional and interventional outcomes.

    Science.gov (United States)

    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)D50nmol/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 in drug-naive adults with no

  6. Discovery of a New Class of Sortase A Transpeptidase Inhibitors to Tackle Gram-Positive Pathogens: 2-(2-Phenylhydrazinylidenealkanoic Acids and Related Derivatives

    Directory of Open Access Journals (Sweden)

    Benedetta Maggio

    2016-02-01

    Full Text Available A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidenebutanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenylhydrazinylidenebutanoic acid (2b, showing an IC50 value of 50 µM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compound resulted 2a, which showed inhibition of about 60% against S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538 and S. epidermidis RP62A at a screening concentration of 100 µM.

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

    Science.gov (United States)

    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

  8. Efficacy of Silybum Marianum Seeds in Ameliorating the Toxic Effects of Aflatoxin B1 in Broilers

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    Omid Fani Makki

    2014-03-01

    Full Text Available Background: This study aims to evaluate the efficacy of silybum marianum seeds (SMSs on blood biochemical profile of broiler chickens contaminated with Aflatoxin B1 (AFB1. Methods: Combinations of three levels of AFB1 (0, 250 and 500 ppb with three levels of SMSs (0, 0.5, and 1.0 % were incorporated into the basal diet (corn and soybean meal. The effect of nine experimental treatments was assessed using 216 One-d-old Ross 308 male broiler chicks in a complete randomized design based on factorial design with 4 replicates of six birds. The individual effects of dietary AFB1 and SMSs on serum biochemistry factors and liver enzymes were evaluated at 35 days of age. Statistical package SAS (9.1 was used to perform the analysis. Results: The main effects of uric acid, glucose, total bilirubin and liver enzymes (such as; aspartate amino-transferase (AST, alanine amino-transaminase (ALT and γ-glutamyl transferase (GGT in groups received different levels of AFB1 significantly increased (P<0.01. In contrast, albumin, direct bilirubin, calcium, and phosphorus significantly decreased (P<0.05. However, the SMSs supplemented diets significantly decreased uric acid, glucose, AST and GGT enzymes compare to control group (P<0.01. Conclusion: SMSs might prevent the adverse effects of AFB1 in contaminated food and improve safety and quality of poultry products for human use.

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

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    Gharib Ola

    2009-11-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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.

  11. Monitoring the Therapeutic and Protective Role of the Anti oxidative Nutritional Factor β Carotene in gamma-Irradiated Rats

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Mansour, H.H.

    2008-01-01

    Carotenoids are those substances, synthesized, only in plants that serve to protect the plants from free radicals. β-carotene, one of the carotenoids, has been thought to be of value to humans and other species, not only as precursors to vitamin A, but also for having excellent antioxidant properties. Four groups of rats were used to gain insight into the protective action of carotenes: control, β-carotene treated (30 mg/ kg body wt for 10 days), irradiated (4 fractions, each of 1.5 Gy gamma-rays during 10 days) and protracted group: rats received the same fractionated gamma-rays at the same time gavaged with β-carotene along the 10 days. Irradiated rats revealed significant decreases in p-carotene and glutathione (GSH) concentrations and significant increases in the activities of blood alkaline phosphatase (ALP), acid phosphatase (ACP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), catalase and contents of blood thiobarbituric acid-reactive substances (TBARS). In liver , tissue, TBARS content and catalase activity were raised while GSH was declined. The oral intake of β-carotene to irradiated rats was found to maintain the parameters measured near the control mean levels; i.e., increased content of blood β-carotene and GSH and modulated activities of ALP, ACP, ALT, GGT, catalase and TBARS level. It also, modulated the alterations of liver TBARS, catalase and GSH. Conclusion: β-carotene therapy significantly modulates oxidative damage induced by ionising radiation in rats

  12. Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study

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    Wagner Ludwig

    2011-06-01

    Full Text Available Abstract Background Type 2 diabetes is associated with increased levels of Angiopoietin-2 (Ang-2 and soluble Tie-2 (sTie-2, but its impact on vascular disease is still unknown. This study aimed to further explore the associations of Ang-2 and sTie-2 with metabolic control and diabetic complications. Methods In a cross-sectional designed study, levels of Ang-2 and sTie-2 as well as their relationships to cardiometabolic parameters were determined in 80 type 2 diabetic subjects (age 65 ± 7 years, female 47.4%. Results After controlling for age and BMI, Ang-2 levels were associated with levels of sTie-2, diastolic blood pressure, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR, creatinine, glomerular filtration rate (GFR, and gamma-glutamyl transferase (GGT (all p 1c, fasting plasma glucose and insulin, HOMA-IR, triglyceride, and liver function parameters (all p 1c, insulin levels, and HOMA-IR (p Conclusions Ang-2 is independently associated with levels of GGT while sTie-2 is independently associated with levels of HbA1c, plasma insulin and HOMA-IR in type 2 diabetic subjects. Therefore we suggest that the associations of Ang-2 and sTie-2 with type 2 diabetes are based on different patho-physiological mechanisms.

  13. Antioxidant activity of lycopene extracted from tomato pomace toward gamma irradiation hazards in male albino rats

    International Nuclear Information System (INIS)

    Saad, T.M.M.; EL MASRY, F.S.

    2005-01-01

    The present study aims to evaluate the anti oxidative activity of lycopene extracted from tomato pomace against hazards induced by gamma irradiation. Male Swiss albino rats were orally administered by lycopene (1.2 mg/rat/day) using suitable stomach tube 7 days before exposure to a sublethal single dose (6.5 Gy) of whole body gamma radiation. Lipid peroxides (MDA) levels in plasma, reduced glutathione (GSH) content and superoxide dismutase activity in blood were determined, as well as serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase activity (GGT) were investigated 7 and 15 days post-irradiation and/or lycopene administration. The results revealed that exposure to ionizing radiation resulted in significant elevation in plasma levels of MDA, serum ALT, AST, ALP and GGT, as well as significant reduction in GSH content and superoxide dismutase activity in blood. Administration of lycopene by using suitable stomach tube pre-irradiation has significantly ameliorated the radiation-induced disturbances in all the investigated parameters

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

    Science.gov (United States)

    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.

  15. A cross-sectional study of the relationship between serum liver enzymes level and the incidence of impaired fasting glucose in males and females.

    Science.gov (United States)

    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.

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

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    Nor Aziyah Mat-Rahim

    2017-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  18. Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels.

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    Eun Young Park

    Full Text Available We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and gamma-glutamyl transferase (GGT. Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI: AST, 2.37 [1.20-4.67]; GGT, 1.91 [1.17-3.13]. Only GGT level (odds ratio 6.04 [3.68-9.94], SI 2.33 [1.24-4.41] was significantly elevated when the effect of moderate drinking (20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12-6.61]. The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.

  19. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

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    Jan Muhammad Shah

    2016-10-01

    Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

  20. The Impact of 10 weeks of Aerobic Exercise and Supplementation of Green Tea on Lipid Profile, Insulin Resistance and Liver Enzymes (GGT, ALT, AST in Obese Diabetic Women (type 2

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    M Izadi Ghahfarokhi

    2015-05-01

    Conclusions: Green tea supplements with aerobic training were effective in controlling obesity and type 2 diabetes. By increasing the duration of the exercise and supplementation, it may find desirable results on serum cholesterol and triglycerides.

  1. The Effects of Short-Term Intensive Exercise on Levels of Liver Enzymes and Serum Lipids in Kick Boxing Athletes

    Directory of Open Access Journals (Sweden)

    Ömer Kaynar

    2016-03-01

    Full Text Available Objective: In this study, it was aimed to evaluate the ef­fects of short-term intensive exercise on liver enzymes and serum lipid levels with kick boxing athletes. Methods: 23 voluntary athletes who were between the ages of 15-46 and who engaged in kick–boxing have tak­en place this study. Athletes were made to do 45 minutes of warming-up, breathing, and stretching and 50 minutes of technical and tactical practices and then they were made to do a training match, which is equal to a 2 min­utes 3 circuits (1 minute rest kick-box match. In venous blood samples which were taken from athletes before and after training, aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP and gamma glutamine transpeptidase (GGT, enzyme activity and total cholesterol, high-density lipoprotein-cholesterol (HDL-C, low density lipoprotein-cholesterol (LDL-C and triglycerides serum levels were analyzed via spectropho­tometric method in Beckman Coulter AU 5800 auto ana­lyzer. Body composition measurements of athletes were made with Tanita TBF 300 brand device, which works with bio-impedance analysis (BIA system. Results: As a result of our study, statistically increases in serum ALT, AST, ALP and GGT enzyme activities and in serum total cholesterol, HDL-C and LDL-C levels were detected following short-term intensive exercise, but no significant difference was observed in TG levels after in­tensive exercise. Conclusion: The blows to the abdomen during kickbox­ing sports competitions result in increased liver enzymes and increased serum lipids may occur to meet energy de­mand of the body during exercise.

  2. Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes

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    Debmalya Sanyal

    2015-01-01

    Full Text Available Context: The perception of non-alcoholic fatty liver disease (NAFLD as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis. Aims: To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT, new onset treatment naive T2DM and normal glucose tolerance (NGT with and without NAFLD. Settings and Design: Cross-sectional clinic-based study. Subjects and Methods: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients. Statistical Analysis Used: Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables, Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively. Results: NAFLD was significantly associated with higher alanine aminotransferase (ALT and gamma-glutamyl transferase (GGT but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT 40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample. Conclusions: Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary

  3. Effect of Terminalia arjuna bark powder on some diagnostic enzymes in buffalo (Bubalus bubalis ingesting arsenic contaminated water and fodder

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    Subrat Kumar Dash

    2016-10-01

    Full Text Available Aim: The study investigated the effect of Terminalia arjuna bark powder on some diagnostic enzymes related to hepatic and muscle function in buffaloes ingesting arsenic contaminated water and fodder in an arsenic affected area. Materials and Methods: A total of 25 samples of tube well water, fodder and buffalo blood were collected through a survey from arsenic contaminated areas and 20 samples from the uncontaminated, i.e., control areas of Ludhiana district, Punjab for determination of arsenic concentration. A total of 30 buffaloes (selected from above 45 animals were divided into three groups of 10 each on the basis of blood arsenic level, viz., control group: Clinically healthy buffaloes from the uncontaminated area with the blood arsenic level within the normal limit (0-0.05 ppm; Arsenic exposed group: Buffaloes exposed to arsenic through intake of contaminated water and fodder in the arsenic affected area with the blood arsenic level above the normal limit of 0-0.05 ppm; treatment group: Arsenic exposed buffaloes treated with T. arjuna bark powder orally at 42 mg/kg b.w. OD for 30 days. Single blood samples were collected from control and arsenic exposed groups. Blood samples from the treatment group were collected on 0, 15th, and 30th day of treatment along with one sample on the 45th day, i.e., after withdrawal of treatment. Activities of alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT, lactate dehydrogenase (LDH, and creatine kinase (CK were assayed in plasma. Results: Significantly (p<0.05 higher arsenic concentration was observed in tube well water, fodder and buffalo blood samples collected from the arsenic contaminated area. A significant positive correlation was noticed between arsenic concentrations of tube well water, fodder and untreated buffalo blood samples, collected from the arsenic affected area. ALP, GGT, LDH, and CK activities were significantly (p<0.05 increased in the arsenic exposed buffaloes compared to

  4. Effects of erythromycin on γ‐glutamyl cysteine synthetase and interleukin‐1β in hyperoxia‐exposed lung tissue of premature newborn rats

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    Cheng Cai

    2014-09-01

    Conclusions: Changes in oxidant‐mediated IL‐1 beta and GSH are involved in the development of hyperoxia‐induced lung injury. Erythromycin may up‐regulate the activity of γ‐GCS, increasing the expression of GSH, inhibiting the levels of oxidant‐mediated IL‐1 beta and alleviating hyperoxia‐induced lung injury via an antioxidant effect.

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

    NARCIS (Netherlands)

    C. Torino (Claudia); F.U.S. Mattace Raso (Francesco); J.L.C.M. van Saase (Jan); M. Postorino (Maurizio); G.L. Tripepi (Giovanni); F. Mallamaci (Francesca); C. Zoccali (Carmine)

    2016-01-01

    textabstractAlkaline 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

  6. Effects of erythromycin on γ-glutamyl cysteine synthetase and interleukin-1β in hyperoxia-exposed lung tissue of premature newborn rats

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    Cheng Cai

    2014-09-01

    Full Text Available Objetivo: Explorar o efeito da eritromicina sobre lesões pulmonares induzidas por hiperóxia. Métodos: Uma prole de ratos Sprague-Dawley (SD prematuros com um dia de vida foi dividida aleatoriamente em quatro grupos: grupo 1 ar + cloreto de sódio, grupo 2 ar + eritromicina, grupo 3 hiperóxia + cloreto de sódio e grupo 4 hiperóxia + eritromicina. Com um, sete e 14 dias de exposição, foram detectadas Glutationa (GSH e Interleucina-1 beta (IL-1 beta pelo ensaio imunossorvente ligado à enzima (ELISA, e o ácido bicinconinico (BCA foi utilizado para detectar a proteína GSH. O mRNA da γ-glutamil-cisteina-sintetase (γ-GCS foi detectado por reação em cadeia da polimerase via transcriptase reversa (RT-PCR. Resultados: Comparadas ao grupo 1, as expressões do mRNA da GSH e da γ-GCS no grupo 3 aumentaram significativamente com um e sete dias de exposição (p < 0,05, porém a expressão de mRNA da γ-GCS diminuiu significativamente aos 14 dias; a expressão de IL-1 beta no grupo 3 aumentou significativamente aos 7 dias de exposição (p < 0,05 e diminuiu significativamente aos 14 dias. Comparadas ao grupo 3, as expressões do mRNA da GSH e da γ-GCS no grupo 4 aumentaram significativamente com um, sete e 14 dias de exposição (p < 0,05, porém as expressões de GSH mostraram uma tendência de queda aos 14 dias; a expressão de IL-1 beta no grupo 4 foi reduzida significativamente com um e sete dias de exposição (p < 0,05. Conclusões: As variações de IL-1 beta e GSH mediadas por oxidantes estão envolvidas no desenvolvimento de lesão pulmonar induzida por hiperóxia. A eritromicina poderá regular positivamente a atividade da γ-GCS, aumentando a expressão de GSH, inibindo os níveis de interleucina-1beta mediada por oxidante e aliviando a lesão pulmonar induzida por hiperóxia por meio de um efeito antioxidante.

  7. Effects of erythromycin on γ-glutamyl cysteine synthetase and interleukin-1β in hyperoxia-exposed lung tissue of premature newborn rats.

    Science.gov (United States)

    Cai, Cheng; Qiu, Gang; Gong, Xiaohui; Chen, Yihuan; Zhao, Huanhu

    2014-01-01

    To explore the effect of erythromycin on hyperoxia-induced lung injury. One-day-old preterm offspring Sprague-Dawley (SD) rats were randomly divided into four groups: group 1, air + sodium chloride; group 2, air + erythromycin;group 3, hyperoxia + sodium chloride; and group 4, hyperoxia + erythromycin. At one, seven, and 14 days of exposure, glutathione (GSH) and interleukin-1 beta (IL-1 beta) were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and bicinchoninic acid (BCA) was used to detect GSH protein. γ-glutamine-cysteine synthetase (γ-GCS) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Compared with group 1, expressions of GSH and γ-GCS mRNA in group 3 were significantly increased at one and seven days of exposure (p < 0.05), but expression of γ-GCS mRNA was significantly reduced at 14 days; expression of IL-1 beta in group 3 was significantly increased at seven days of exposure (p < 0.05), and was significantly reduced at 14 days. Compared with group 3, expressions of GSH and γ-GCS mRNA in group 4 were significantly increased at one, seven, and 14 days of exposure (p < 0.05), but expressions of GSH showed a downward trend at 14 days; expression of IL-1 beta in group 4 was significantly reduced at one and seven days of exposure (p < 0.05). Changes in oxidant-mediated IL-1 beta and GSH are involved in the development of hyperoxia-induced lung injury. Erythromycin may up-regulate the activity of γ-GCS, increasing the expression of GSH, inhibiting the levels of oxidant-mediated IL-1 beta and alleviating hyperoxia-induced lung injury via an antioxidant effect. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  8. A conformational investigation of propeptide binding to the integral membrane protein γ-glutamyl carboxylase using nanodisc hydrogen exchange mass spectrometry

    DEFF Research Database (Denmark)

    Parker, Christine H; Morgan, Christopher R; Rand, Kasper Dyrberg

    2014-01-01

    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...

  9. Prognosis, with evaluation of general biochemistry, of liver disease in lymphoedema cholestasis syndrome 1 (LCS1/Aagenaes syndrome).

    Science.gov (United States)

    Drivdal, Monica; Trydal, Torleif; Hagve, Tor-Arne; Bergstad, Ingunn; Aagenaes, Oystein

    2006-04-01

    To investigate the prognosis of liver disease in Aagenaes syndrome (lymphoedema cholestasis syndrome 1 (LCS1)), which is an autosomal recessive inherited syndrome consisting of neonatal cholestasis with intermittent cholestatic episodes in childhood into adulthood and development of lymphoedema. Forty Norwegian patients are known to have this condition, 25 of whom are alive. A clinical description of the liver disease is supplied with a case-control study. In this paper we review the course of the liver disease in the Norwegian cohort of patients and present results from a case-control study in the patients above 10 years of age. The case-control study was performed on 15 patients without clinical cholestasis (itching and sometimes jaundice) at the time of the study. An evaluation of 11 patients above 15 years of age without chronic biochemical cholestasis (increased alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and/or serum bile acids) was also carried out. For each patient one randomly identified control person was included (15 in one study, 11 in the other). Cirrhosis with either transplantation or death in infancy or early childhood occurred in six patients; slowly developing cirrhosis occurred in three patients. Two patients may be in the process of developing cirrhosis. Significantly increased ALP and GGT levels were found in patients with normal liver biochemistry in the preceding years when compared with the case control group. Additionally, albumin was found to be lower in older patients. Compared with that for other types of hereditary neonatal cholestasis, patients with LCS1 have a relatively good prognosis. More than 50% can expect a normal life span.

  10. Modulatory Role of Folic Acid Administration on Some Biochemical and Hormonal Disturbances in Rats

    International Nuclear Information System (INIS)

    Mohamed, N.E.

    2013-01-01

    Fried food which is the most easier and fast food prepared especially out the home door became a serious risk because of the high concentrations of acrylamide identified mainly in potatoes and grains based foods that are cooked at very high temperature e.g. frying, grilling or baking. In the current study, forty eight adult male rats were classified into the following groups (12 rats/group): 1- control group: rats received only normal diet, 2- folic acid group: rats received folic acid (25 mg/kg/day) using stomach tube throughout the experimental period (ten weeks), 3- acrylamide group: rats received acrylamide (30 mg/kg) using stomach tube for ten weeks and 4- folic acid and acrylamide group: rats received folic acid (25 mg/kg/day) along with acrylamide (30 mg/kg./day) using stomach tube through the experimental period. After five and ten weeks of the experimental period, the animals were sacrificed by decapitation then thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD) and glutathione (GSH) were determined in testis and brain homogenates. Also, gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), acid phosphatase (ACP), total protein, albumin, urea, creatinine, triiodothyronine, thyroxine, testosterone and estradiol were determined in serum. In addition, histological examinations of testis and brain tissues were examined. The results obtained revealed that administration of acrylamide induced significant increase in TBARS, and reduction in SOD and GSH in testis and brain homogenate. Also, significant increase in GGT, ALP, ACP, urea, creatinine and estradiol levels in serum was recorded. A marked significant decrease in total protein, albumin, T3, T4 and testosterone in serum was observed in acrylamide group. Histological investigations showed degenerative changes in both testis and brain tissues through the experimental period. Significant improvements in biochemical and histological structure were recorded in acrylamide groups

  11. Infectious mononucleosis and hepatic function

    Science.gov (United States)

    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

  12. Investigation of liver tissue and biochemical parameters of adult wistar rats treated with Arctium lappa L.

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    Fabrícia Souza Predes

    2009-04-01

    Full Text Available This study was carried out to evaluate the effects of Arctium lappa L. (burdock on the liver of adult male Wistar rats as measured by light microscopy and biochemical parameters. The rats received the extract in water bottles at doses of 10 or 20 g/L daily for 40 days. There were no significant changes in the plasma levels of albumin, aspartate transaminase (AST, alanine transaminase (ALT, gamma glutamyl transferase (GGT, total protein, total cholesterol, urea, uric acid, triacylglycerol, calcium, phosphorus, chlorine and direct bilirubin. The morphological analysis did not reveal histopathological alterations in liver tissue. Both biochemical and morphological data did not indicate A. lappa toxicity.A bardana (Arctium lappa L é uma planta trazida do Japão e aclimatada no Brasil, e é extensamente utilizada na medicina popular em todo mundo. Este estudo foi realizado para avaliar os possíveis efeitos da A. lappa no fígado e nos parâmetros bioquímicos plasmáticos em ratos Wistar adultos. Estes receberam a infusão de bardana nas doses de 10 ou 20 g de folhas secas /L de água, por 40 dias. Não houve alteração significativa nos níveis plasmáticos de albumina, aspartato transaminase (AST, alanina transaminase (ALT, gamma glutamil transferase (GGT, proteínas totais, colesterol total, uréia, ácido úrico, triglicérides, cálcio, fósforo, bilirrubina direta e cloro. A análise morfológica não revelou alterações histopatológicas no fígado. Os dados bioquímicos e morfológicos não indicaram a toxicidade da bardana.

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

    Energy Technology Data Exchange (ETDEWEB)

    Colacino, Justin A.; Arthur, Anna E.; Ferguson, Kelly K.; Rozek, Laura S., E-mail: rozekl@umich.edu

    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. - 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.

  14. Fasting conditions: Influence of water intake on clinical chemistry analytes.

    Science.gov (United States)

    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.

  15. Liver enzymes and markers of inflammation in Nigerian adults with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Udenze Ifeoma Christiana

    2015-01-01

    Full Text Available Aims and objectives: The aim of this study is to determine the plasma levels of the liver enzymes alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT, and lactate dehydrogenase (LDH in people with metabolic syndrome and to determine the association between the liver enzymes and obesity, insulin resistance, interleukin 6 (IL-6, and C-reactive protein (CRP in adult Nigerians with metabolic syndrome. Materials and Methods: This was a case control study of 50 adult men and women with metabolic syndrome, and 50 age- and sex-matched males and females without metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Program (NCEP-Adult Treatment Panel III (ATPIII criteria. Written informed consent was obtained from the participants. Sociodemographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an overnight fast. The ethics committee of the Lagos University Teaching Hospital in Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the student′s t-test. Regression and correlation analysis were used to determine the associations between variables. Statistical significance was set at P < 0.05. Results: There was a statistically significant increase in the liver enzymes ALP (P = 0.031, ALT (P = 0.019, and GGT (P = 0.037, as well as in the inflammatory markers CRP (P = 0.019 and the cytokine IL-6 (P = 0.040 between the two study groups. ALP and ALT showed significant correlation with waist circumference, BMI, fasting insulin, and waist/hip ratio (P < 0.05. Multivariate regression also identified ALT, AST, and ALP to be associated with IL-6 and CRP (P < 0.05. Conclusion: Liver enzyme levels were increased in metabolic syndrome and associated with obesity, fasting insulin, and CRP. Elevated liver enzymes may indicate dysmetabolism and increased

  16. Effect of Spirulina supplementation on plasma metabolites in crossbred and purebred Australian Merino lambs

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    A.E.O. Malau-Aduli

    2015-06-01

    Full Text Available The effect of supplementing purebred and crossbred Merino lambs with Arthrospira platensis (Spirulina on plasma metabolite concentrations under pasture-based management system and the influences of sire breed and sex were investigated. A completely randomized experimental design balanced by 4 sire breeds (Merino, White Suffolk, Dorset and Black Suffolk, 3 Spirulina supplementation levels (0, 100 and 200 ml representing the control, low and high, respectively and 2 sexes (ewe and wether lambs was utilised. All lambs had ad libitum access to the basal diet of ryegrass pastures and barley. Lambs in the treatment groups were individually drenched daily with Spirulina prior to being released with the control group of lambs for grazing over a 6-week period following a 3-week adjustment phase. At the start and completion of the feeding trial, blood samples were centrifuged and plasma metabolites measured. Data were analysed with Spirulina supplementation level, sire breed, sex and their second-order interactions fitted as fixed effects and metabolite concentrations as dependent variables. Gamma-glutamyl transferase (GGT concentrations decreased (from 79.40 to 69.25 UI and glucose increased (from 3.81 to 4.19 mmol/L as the level of Spirulina supplementation increased from 0 ml in the control to 200 ml in the high treatment groups (P < 0.05. Lambs supplemented at low Spirulina levels had the highest creatinine concentrations (61.75 μmol/L. Interactions between sex and supplementation level significantly affected glucose, aspartate aminotransferase (AST and Mg concentrations (P < 0.05, while sire breed and supplementation level interactions influenced albumin to globulin (A/G ratio, creatinine and GGT concentrations. It was demonstrated that Spirulina supplementation does not negatively impact lamb health and productivity.

  17. Oxidative stress response of Forster's terns (Sterna forsteri) and Caspian terns (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney, and brain

    Science.gov (United States)

    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.

  18. Diagnostic performance of traditional hepatobiliary biomarkers of drug-induced liver injury in the rat.

    Science.gov (United States)

    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. Kombucha Tea Ameliorates Trichloroethylene Induced Hepatic Damages in Rats via Inhibition of Oxidative Stress and Free Radicals Induction

    International Nuclear Information System (INIS)

    Gharib, O.A.; Gharib, M.A.

    2008-01-01

    Kombucha Tea (KT) is reported to exhibit a wide variety of biological effects, including antioxidant. Evidence shows the important role of oxidative stress in the hepatic damage. The aim of this study is to investigate the possible protective effects of oral administration of KT in rats with trichloroethylene (TCE)-induced damage for ten consecutive days. Hepatic damage was evaluated by measuring total free radicals levels, biochemical and histological examinations. Serum gamma glutamyl transferase (GGT) activity (the hepatic damage marker), total protein, albumin and globulin as well as malonaldehyde (MDA), glutathione (GSH) content, nitric oxide (NO) concentration were evaluated in liver tissue homogenates. Total free radicals concentration in blood was examined by electron spin resonance (ESR). Total protein, DNA concentration, cell number and cell size in liver tissues were also examined. The rats orally administrated with TCE for ten days indicates hepatic damage changes, an increase in blood total free radicals concentration was observed, serum GGT activity, liver MDA, NO levels, total protein and decreased GSH content, DNA concentration and cell number. This accompanied with an increase in cell size of liver tissues, whereas KT reversed these effects. Furthermore, KT inhibits the concentration of total free radicals in blood and decreasing the increment of MDA and NO concentration. Histological studies reveal partial healing in those rats treated by KT after oral administration with TCE. The present results suggest that KT ameliorates TCE induced hepatic damage in rats probably due to its content of glucuronic, acetic acid and B vitamins via inhibition of oxidative stress and total free radicals

  20. Grape Seed oil as Anti hepatic and Anti renal Dysfunction agent in Paracetamol Administrated Rats

    International Nuclear Information System (INIS)

    Farag, M.F.; Osman, N.N.; Darwish, M.M.

    2010-01-01

    The protection conferred by dietary grape seed oil (GSO) against paracetamol (PCL)-induced liver and kidney dysfunction have been evaluated in adult male albino Wistar rats. The animals (180-200 g) were randomly divided into four groups of seven rats each. Group l: normal control, group II: animals received GSO (3.7 g Kg-1 body wt/day orally), group III: animals received PCL (4 g Kg-1 body wt/day orally) and group IV: animals received PCL plus GSO. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), urea (U), creatinine (Cr) and albumin (A) levels in serum and blood urea nitrogen (BUN) were measured. In addition, the levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of superoxide dismutase (SOD) and catalase (CAT) in the liver and kidney homogenates were chosen for assessing. The PCL induced a significant elevation in the serum AST, ALT, AP and GGT. Moreover, a significant increase in serum U, Cr, A and BUN were evident. Furthermore, a significant rise in TBARS, while a significant declined activity of SOD and CAT and GSH content in liver and kidney homogenates were also observed. Oral administration of GSO resulted in a significant reduction in liver and kidney markers in serum, BUN as well hepatic and renal TBARS accompanied by a significant improvement in the tissue antioxidants and A, when compared with PCL damaged rats. It was suggested that GSO has potent hepatic and renal protective effects against the oxidative damage induced in rats due to PCL treatment, perhaps by its antioxidative effects hence eliminating the deleterious effects of PCL.

  1. In vitro Effects of Four Native Brazilian Medicinal Plants in CYP3A4 mRNA Gene Expression, Glutathione Levels, and P-Glycoprotein Activity

    Science.gov (United States)

    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 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

  2. In vitro effects of four native Brazilian medicinal plants in CYP3A4 mRNA gene expression, glutathione levels and P-glycoprotein activity.

    Directory of Open Access Journals (Sweden)

    Andre Luis Dias Araujo Mazzari

    2016-08-01

    Full Text Available Erythrina mulungu Benth. (Fabaceae, Cordia verbenacea A. DC. (Boraginaceae, Solanum paniculatum L. (Solanaceae and Lippia sidoides Cham. (Verbenaceae are medicinal plants 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 (100μg/mL of their 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 (two-fold decrease, p<0.05, this being correlated with an antagonist effect upon hPXR (EC50 = 0.38mg/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 later 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.

  3. Assessment of Vitamin D status in a group of Egyptian children with non alcoholic fatty liver disease (multicenter study).

    Science.gov (United States)

    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.

  4. Contribution of Inflammation, Oxidative Stress, and Antioxidants to the Relationship between Sleep Duration and Cardiometabolic Health.

    Science.gov (United States)

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

    International Nuclear Information System (INIS)

    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. - 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

  6. Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

    Directory of Open Access Journals (Sweden)

    Elias Adikwu

    2018-03-01

    Full Text Available Objective: Hepatotoxicity is a clinical challenge associated with the use of efavirenz (EFV. This study investigated the effects of n-acetylcysteine (NAC, vitamins C and E on EFV-induced hepatotoxicity in albino rats. Methods: Rats were divided into groups and administered with NAC (20mg/kg, Vit C (50mg/kg, Vit  E (50mg/kg, Vit C+ E and 60mg/kg of EFV respectively. Rats were also divided into groups and pretreated with NAC, Vit C, E, and combined doses of Vit C+E prior to treatment with EFV for 15 days respectively. After drug administration rats were sacrificed and serum was collected and evaluated for liver function parameters. Rats were dissected, liver was collected weighed and evaluated for alkaline phosphatase (ALP, alanine aminotransferase (AST, aspartate aminotransferase (ALT, gamma glutamyl transferase (GGT, lactate dehydrogenase (LDH, malondialdehyde (MDA, super oxide dismutase (SOD, catalase (CAT, glutathione (GSH, gluthatione peroxidase (GPX levels and pathological damage. Results: Effects were not significant (p>0.05 on body and liver weights, however, the levels of AST, ALT, AST, GGT, LDH, CB, TB and MDA were increased significantly (p<0.05 whereas SOD, CAT, SOD, GSH and GPX were decreased significantly (p<0.05 in EFV-treated rats in comparison to control. The liver of EFV-treated rats showed necrosis of hepatocytes. Nevertheless, EFV-induced alterations in the above parameters were significantly (p<0.05 ameliorated in antioxidants pretreated rats.  The combined doses of Vit C and E produced the best and significant (p<0.05 ameliorative effects in comparison to their individual doses. Conclusion: This study shows the prospects of antioxidants as candidates for the treatments of efavirenz-induced hepatotoxicity.

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

    Science.gov (United States)

    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.

  8. Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells

    Directory of Open Access Journals (Sweden)

    Megan L. Steele

    2013-01-01

    This study compares four known Nrf2 activators, R-α-Lipoic acid (LA, tert-butylhydroquinone (TBHQ, sulforaphane (SFN and Polygonum cuspidatum extract containing 50% resveratrol (PC-Res for their effects on astroglial release of GSH and CysGly. GSH levels increased dose-dependently in response to all four drugs. Sulforaphane produced the most potent effect, increasing GSH by up to 2.4-fold. PC-Res increased GSH up to 1.6-fold, followed by TBHQ (1.5-fold and LA (1.4-fold. GSH is processed by the ectoenzyme, γ-glutamyl transpeptidase, to form CysGly. Once again, SFN produced the most potent effect, increasing CysGly by up to 1.7-fold, compared to control cells. TBHQ and PC-Res both induced fold increases of 1.3, followed by LA with a fold increase of 1.2. The results from the present study showed that sulforaphane, followed by lipoic acid, resveratrol and Polygonum multiflorum were all identified as potent “GSH and Cys-Gly boosters”.

  9. Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease.

    Science.gov (United States)

    Miyahara, Satoshi; Saito, Mitsumasa; Kanemaru, Takaaki; Villanueva, Sharon Y A M; Gloriani, Nina G; Yoshida, Shin-ichi

    2014-08-01

    Weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic Leptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of Weil's disease. In this work, we obtained three-dimensional images of infected hamster livers using scanning electron microscope together with freeze-cracking and cross-cutting methods for sample preparation. The images displayed the corkscrew-shaped bacteria, which infiltrated the Disse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ-glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non-pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co-incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

  10. Intestinal endotoxins as co-factors of liver injury in obstructive jaundice.

    Science.gov (United States)

    Mentes, B B; Tatlicioglu, E; Akyol, G; Uluoglu, O; Sultan, N; Yilmaz, E; Celebi, M; Taneri, F; Ferahkose, Z

    1996-01-01

    The concept of endotoxin-mediated rather than direct liver injury in biliary obstruction was investigated using the experimental rat model of bile duct ligation (BDL) and small bowel bacterial overgrowth (SBBO). Small identical doses of intravenous endotoxin (bacterial LPS) caused a significantly more severe liver injury in rats with BDL, compared with sham-operated rats, suggesting the possible contribution of LPS in this type of liver damage. BDL was then combined with surgically created jejunal self-filling blind loops, which resulted in SBBO. Plasma LPS level increased significantly, and once again a more severe liver injury, determined by liver histology and serum gamma-glutamyl transpeptidase levels, was observed compared with the control group of rats with BDL+self-emptying blind loops. The data presented suggest that small amounts of exogenous LPS and/or the ordinarily innocous amounts of LPS constantly absorbed from the intestinal tract may be critical in the hepatic damage caused by obstruction of the biliary tract.

  11. Utilization of Basil Extract as a Radioprotector in Male Rats

    Energy Technology Data Exchange (ETDEWEB)

    Farag, M. F.S. [Food Irradiation Research Dep. National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)

    2013-01-15

    Man is exposed to natural radiations from cosmic or terrestrial origins. Furthermore, it is well known that the gamma irradiation-induced biochemical alteration depends mostly on oxidative stress. Basil or sweet basil (Ocimum basilicum) is known to have numerous pharmacological activities. Therefore, the present study was carried out to investigate the radioprotective activity of basil in albino rats. The effect of basil aqueous extract (BAE) was evaluated on hepatic marker enzymes, sex hormones, lipid profile and antioxidant status. The results showed that - rays caused a significant increase in serum level of alanine and aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase (ALT, AST, ALP and GT), cholesterol (TC), triglyceride (TG), low and very low density lipoprotein cholesterol (LDL-C and VLDL-C) and thiobarbituric acid reactive substances (TBARS). A significant decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in serum was observed, compared with control group. Moreover, - rays induced a significant drop in the serum sex hormones levels testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH). The BAE administered orally to rats has significantly modulated all the radiation-induced biochemical alterations. These findings showed that basil would exert a radioprotective properties.

  12. Utilization of Basil Extract as a Radioprotector in Male Rats

    International Nuclear Information System (INIS)

    Farag, M.F.S.

    2013-01-01

    Man is exposed to natural radiations from cosmic or terrestrial origins. Furthermore, it is well known that the gamma irradiation-induced biochemical alteration depends mostly on oxidative stress. Basil or sweet basil (Ocimum basilicum) is known to have numerous pharmacological activities. Therefore, the present study was carried out to investigate the radioprotective activity of basil in albino rats. The effect of basil aqueous extract (BAE) was evaluated on hepatic marker enzymes, sex hormones, lipid profile and antioxidant status. The results showed that - rays caused a significant increase in serum level of alanine and aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase (ALT, AST, ALP and GT), cholesterol (TC), triglyceride (TG), low and very low density lipoprotein cholesterol (LDL-C and VLDL-C) and thiobarbituric acid reactive substances (TBARS). A significant decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in serum was observed, compared with control group. Moreover, - rays induced a significant drop in the serum sex hormones levels testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH). The BAE administered orally to rats has significantly modulated all the radiation-induced biochemical alterations. These findings showed that basil would exert a radioprotective properties.

  13. Evaluation of haemato-biochemical and oxidative indices in naturally infected concomitant tick borne intracellular diseases in dogs

    Directory of Open Access Journals (Sweden)

    Kalyan Sarma

    2015-01-01

    Full Text Available Objective: To explore haemato-biochemical and oxidative stress indices due to concomitant tick borne intracellular diseases in dogs presented at Referral Veterinary Polyclinic, Indian Veterinary Research Institute, Bareilly during May 2010 to May 2012. Methods: Microscopy of Giemsa blood smear and ELISA test (SNAP 4D伊 were carried out in suspected cases to confirm haemo-parasitic infection. Blood and serum samples were analyzed for oxidative stress indices and haemato-biochemical changes. All the ailing conditions were recorded to investigate the clinical pattern of concomitant tick borne diseases. Ultrasonographic study was carried out to obtain the hepatic involvement. Results: Examination of 3 650 dogs revealed that 2.77% dog were positive for various tick borne diseases, out of which 21.78% were with concomitant infection. Clinical symptoms were noted with overall mean clinical score of 9.95依0.30. Ultrasonographic examination revealed hepatomegaly, distension of gall bladder, and ascites. Haemato-biochemical evaluation confirmed anaemia, leucopenia, thrombocytopenia, hypoproteinemia, hypoalbuminemia, hyperglobulinemia and hyperbilirubinemia with increased serum alanine amino transferase, alkaline phosphatase and gamma-glutamyl transpeptidase in concomitant infected dogs. The lipid peroxidation level of concomitant infection was significantly higher (P<0.05 than healthy group whereas superoxide dismutase, glutathione-reduced and catalase activity in concomitant infected group were decreased. Conclusions: The severity of infection was more pronounced in dogs harboring Ehrlichia, Babesia and Hepatozoon and the oxidative stress may have a pathophysiological role in concomitant infection in dogs.

  14. Protective effect of polysaccharide from maca (Lepidium meyenii) on Hep-G2 cells and alcoholic liver oxidative injury in mice.

    Science.gov (United States)

    Zhang, Lijun; Zhao, Qingsheng; Wang, Liwei; Zhao, Mingxia; Zhao, Bing

    2017-06-01

    To study the characterization and hepatoprotective activity of polysaccharide from maca (Lepidium meyenii), the main polysaccharide from maca (MP-1) was obtained by DEAE-52 cellulose column. The average molecular weight of MP-1 was 1067.3kDa and the polysaccharide purity was 91.63%. In order to assess the antioxidant activities of MP-1, four kinds of methods were used, including scavenging hydroxyl radical, DPPH, superoxide anion radical, and FRAP, and the results indicated high antioxidant activities. Furthermore, hepatoprotective activity of MP-1 was studied both in vitro and vivo. In vitro, the alcohol induced Hep-G2 cells model was established to evaluate the protective effect of MP-1, which demonstrated MP-1 can alleviate alcohol damage in Hep-G2 cells. In vivo, the Institute of Cancer Researcch (ICR) mice were used to evaluate hepatoprotecive effects of MP-1 on alcoholic liver disease (ALD). Supplement with MP-1 supressed the triglyceride level both in serum and in hepatic tissue. In addition, MP-1 ameliorated serous transaminases increase induced by alcohol, including aspartate transaminase, alanine aminotransferase, and γ-glutamyl transpeptidase. Moreover, MP-1 also dramatically increased the superoxide dismutase, glutathione peroxidase, and glutathione s-transferase levels in alcoholic mice. Meantime, histopathologic results MP-1 lighten inflammation induced by alcohol. These results indicate that MP-1 possesses hepatoprotective activity against hepatic injury induced by alcohol. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Common Bile Duct Obstruction Secondary to a Periampullary Diverticulum

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    Anastasios J. Karayiannakis

    2012-07-01

    Full Text Available Periampullary duodenal diverticula are not uncommon and are usually asymptomatic although complications may occasionally occur. Here, we report the case of a 72-year-old woman who presented with painless obstructive jaundice. Laboratory tests showed abnormally elevated serum concentrations of total and direct bilirubin, of alkaline phosphatase, of γ-glutamyl transpeptidase, and of aspartate and alanine aminotransferases. Serum concentrations of the tumor markers carbohydrate antigen 19-9 and carcinoembryonic antigen were normal. Abdominal ultrasonography showed dilatation of the common bile duct (CBD, but no gallstones were found either in the gallbladder or in the CBD. The gallbladder wall was normal. Computed tomography failed to detect the cause of CBD obstruction. Magnetic resonance imaging and magnetic resonance cholangiopancreatography revealed a periampullary diverticulum measuring 2 cm in diameter and compressing the CBD. The pancreatic duct was normal. Hypotonic duodenography demonstrated a periampullary diverticulum with a filling defect corresponding to the papilla. CBD compression by the diverticulum was considered as the cause of jaundice. The patient was successfully treated by surgical excision of the diverticulum. In conclusion, the presence of a periampullary diverticulum should be considered in elderly patients presenting with obstructive jaundice in the absence of CBD gallstones or of a tumor mass. Non-interventional imaging studies should be preferred for diagnosis of this condition, and surgical or endoscopic interventions should be used judiciously for the effective and safe treatment of these patients.

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

    Science.gov (United States)

    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.

  17. Possible Impact of Antioxidant Properties of Cocoa (Theobroma Cacao L.) Against Irradiation - Induced Some Biochemical Disorders in Rats

    International Nuclear Information System (INIS)

    Farag, M.F.S.; Darwish, M.M.

    2016-01-01

    Man is exposed to natural radiations either from cosmic or terrestrial origins. Furthermore, it is well known that the gamma irradiation of animals induce biochemical alterations which depend mostly on oxidative stress. This work aimed at evaluating the radioprotective efficiency of Cocoa (Theobroma cacao L.) against whole body γ-irradiation of rats. The virtue of cocoa aqueous extract (CAE) was given to rats at a dose of 1 g/ kg for 6 weeks to determine changes in hepatic marker enzymes, lipid profile and antioxidant status. The animals exposed to γ-rays exhibited a pronounced increment in serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γ GT), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and liver thiobarbituric acid reactive substance (TBARS). On the other hand, a significant decline was demonstrated in high density lipoprotein cholesterol (HDL-C). A decrease of hepatic reduced glutathione (GSH) content, superoxides dismutase (SOD) and catalase (CAT) activities was sustained. The CAE administered orally to rats has significantly modulated all the radiation-induced biochemical alterations. These findings revealed that cocoa would exert radio-protective properties

  18. Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

    Science.gov (United States)

    El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

    2011-09-01

    Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

  19. Short-Term Systemic Effects of Nose-Only Cigarette Smoke Exposure in Mice: Role of Oxidative Stress

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    Abderrahim Nemmar

    2013-01-01

    Full Text Available Background/Aims: 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. Methods: 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. Results: 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. Conclusion: 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.

  20. Establishment and validation of a predictive nomogram model for non-small cell lung cancer patients with chronic hepatitis B viral infection.

    Science.gov (United States)

    Chen, Shulin; Lai, Yanzhen; He, Zhengqiang; Li, Jianpei; He, Xia; Shen, Rui; Ding, Qiuying; Chen, Hao; Peng, Songguo; Liu, Wanli

    2018-05-04

    This study aimed to establish an effective predictive nomogram for non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. The nomogram was based on a retrospective study of 230 NSCLC patients with chronic HBV infection. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index), calibration plot and decision curve analysis and were compared with the current tumor, node, and metastasis (TNM) staging system. Independent factors derived from Kaplan-Meier analysis of the primary cohort to predict overall survival (OS) were all assembled into a Cox proportional hazards regression model to build the nomogram model. The final model included age, tumor size, TNM stage, treatment, apolipoprotein A-I, apolipoprotein B, glutamyl transpeptidase and lactate dehydrogenase. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with the actual observations. The C-index of the model for predicting OS had a superior discrimination power compared with the TNM staging system [0.780 (95% CI 0.733-0.827) vs. 0.693 (95% CI 0.640-0.746), P  20.0). The proposed nomogram model resulted in more accurate prognostic prediction for NSCLC patients with chronic HBV infection.

  1. Hepatic steatosis in a school population of overweight and obese adolescents.

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    Lira, Ana R F; Oliveira, Fernanda L C; Escrivão, Maria A M S; Colugnati, Fernando A B; Taddei, José A A C

    2010-01-01

    To assess hepatic steatosis by ultrasound method as a concomitant risk factor among overweight adolescents. A case-control study including 83 cases (47 overweight and 36 obese) and 89 controls (normal weight), frequency matched by gender, year of birth, pubertal stage (Tanner 4/5), and income. Cases and controls were selected from 1,420 students enrolled in a Vila Mariana public high school, in São Paulo, Brazil. Must et al. criteria were used for nutritional status classification. Nonalcoholic fatty liver disease was diagnosed through hepatic ultrasonography performed and analyzed by one radiologist. Hepatic enzymatic activities (alanine and aspartate transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase) and direct bilirubin were measured. Eight covariables were fitted into logistic regression models; criterion for inclusion of variables was the association with overweight in the bivariate analyses (p 24 U/L were 10.77 (2.45-47.22) and 4.18 (1.46-11.94), respectively. This is the first population-based study showing that hepatic steatosis is strongly associated with overweight/obesity among adolescents attending a Brazilian public school. The diagnostic tool used in this investigation is a non-invasive method that might be applied to monitor overweight and obese adolescents and to propose actions for preventing more severe hepatic diseases in adulthood.

  2. Pistacia chinensis: A Potent Ameliorator of CCl4 Induced Lung and Thyroid Toxicity in Rat Model

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    Kiran Naz

    2014-01-01

    Full Text Available In the current study protective effect of ethanol extract of Pistacia chinensis bark (PCEB was investigated in rats against CCl4 induced lung and thyroid injuries. PCEB dose dependently inhibited the rise of thiobarbituric acid-reactive substances, hydrogen peroxide, nitrite, and protein content and restored the levels of antioxidant enzymes, that is, catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, γ-glutamyl transpeptidase, and quinone reductase in both lung and thyroid tissues of CCl4 treated rats. Decrease in number of leukocytes, neutrophils, and hemoglobin and T3 and T4 content as well as increase in monocytes, eosinophils, and lymphocytes count with CCl4 were restored to normal level with PCEB treatment. Histological study of CCl4 treated rats showed various lung injuries like rupture of alveolar walls and bronchioles, aggregation of fibroblasts, and disorganized Clara cells. Similarly, histology of CCl4 treated thyroid tissues displayed damaged thyroid follicles, hypertrophy, and colloidal depletion. However, PCEB exhibited protective behaviour for lungs and thyroid, with improved histological structure in a dose dependant manner. Presence of three known phenolic compounds, that is, rutin, tannin, and gallic acid, and three unknown compounds was verified in thin layer chromatographic assessment of PCEB. In conclusion, P. chinensis exhibited antioxidant activity by the presence of free radical quenching constituents.

  3. Current research on progressive familial intrahepatic cholestasis

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    DENG Baocheng

    2015-09-01

    Full Text Available Progressive familial intrahepatic cholestasis (PFIC refers to a heterogeneous group of autosomal-recessive disorders. The estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC-1, PFIC-2, and PFIC-3 are due to mutations in ATP8B1, ABCB11, and ABCB4 genes involved in bile secretion, respectively. Serum gamma-glutamyl transpeptidase is normal in patients with PFIC-1 and PFIC-2, while it is raised in patients with PFIC3. The main clinical manifestation of PFIC is severe intrahepatic cholestasis. PFIC usually appears in infancy or childhood and rapidly progresses to end-stage liver disease before adulthood. Diagnosis of this disease is based on clinical manifestations, liver function tests, liver ultrasonography, liver histology, and genetic testing. Ursodeoxycholic acid therapy is the initial treatment in all PFIC patients to prevent liver damage. In some PFIC1 and PFIC2 patients, biliary diversion may also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation.

  4. Ursodeoxycholic acid for nonalcoholic steatohepatitis.

    Science.gov (United States)

    Wu, Sheng-di; Li, Lei; Wang, Ji-yao

    2012-11-01

    The aim of this study was to evaluate the effects of ursodeoxycholic acid on patients with nonalcoholic steatohepatitis using meta-analysis. PubMed, EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Databases, and article references were searched. We included randomized controlled trials using liver biopsy as a reference standard. We identified three eligible studies. Among histological responses, only lobular inflammation improved in the high-dose ursodeoxycholic acid subgroup compared with the control group [mean deviation (MD): -0.23 (-0.40, -0.06), P=0.008]. However, fibrosis may tend to increase [MD: 0.08 (-0.04, 0.20), P=0.17]. Among biochemical responses, γ-glutamyl transpeptidase reduction was significantly greater in the ursodeoxycholic acid group than in the placebo group, and the reduction tendency was only shown in the high-dose subgroup [MD: -35.58 (-52.60, -18.56), Pursodeoxycholic acid subgroup compared with the control group [MD: 0.43 (0.14, 0.72), P=0.004]. Ursodeoxycholic acid-treated patients did not differ significantly from control patients with regard to alanine transaminase, aspartate aminotransferase, and alkaline phosphatase activities. Adverse events were nonspecific and considered of no major clinical relevance. Ursodeoxycholic acid in monotherapy has no substantial positive effect on nonalcoholic steatohepatitis.

  5. Ursodeoxycholic acid in neonatal sepsis-associated cholestasis

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    Rita Mey Rina

    2014-08-01

    21.0 U/L vs -2.0 (ranged -167 .0 - 85.0 U/L; P= 0.730, median aspartate aminotransferase (AST levels [ 43 .0 (range 14.0-297 .0 U/L vs 150.0 (range 24.0-840.0 U/L; P=0.081, and median gamma-glutamyl transpeptidase (GGf levels [125.0 (48.0-481.0 U/L vs 235.0 (56.0-456.0 U/L; P=0.108. Five neonates in control group died compared to two in the UDCA group (P=0.232. In addition, UDCA did not significantly lengthen the survival time (hazard ratio/HR 3.62; 95%CI 0.69 to 18.77 . Conclusion Ursodeoxycholic acid tends to improve total bilirubin, direct bilirubin, and AST levels in sepsis associated cholestasis .

  6. 1,2,3,4-Tetrahydroisoquinoline protects terminals of dopaminergic neurons in the striatum against the malonate-induced neurotoxicity.

    Science.gov (United States)

    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.

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

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    P. E. Pensel

    2014-01-01

    Full Text Available 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.

  8. Determinants of platelet aggregation in 50-70-year-old men from three Japanese communities.

    Science.gov (United States)

    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.

  9. Pathology and clinicopathology of buffalo against trickle infection with Fasciola gigantica

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    Ening Wiedosari

    1998-06-01

    Full Text Available Eleven male buffalo calves were divided into infected group of 7 animals and non-infected control group of 4 animals. The infected group was then inoculated with trickle doses of 15 Inetacercariae of Fasciola gigantica twice weekly for 32 weeks and killed 36 weeks after first infection. There were no clinical symptoms observed . Infected and non-infected buffaloes, had similar values of packed cell volume, haemoglobin and red blood cell counts . In infected buffaloes, plasma glutamate dehydrogenase enzyme activity increased in proportion to the dregree of hepatocyte destruction level and evidence of necrosis caused by the migrating of immature flukes through the parenchyma prior to their entry into the bile ducts. While the values of plasma glutamyl transpeptidase showed only a minimal rise with a small peak in week 20 as evidenced by histological observation that infected caused limited damage to epithelial surface of the bile duct . These results indicates that, the resistance mechaninisms of buffalo against fasciolosis infection occurred in the liver or before flukes entering into the bile ducts. These results seem to indicate that, in buffalo, resistance mechanisms to fasciolosis infection occured in the liver or before flukes entry into the bile ducts.

  10. Insulin resistance, body composition, and fat distribution in obese children with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yang, Hye Ran; Chang, Eun Jae

    2016-01-01

    The aim of this study was to evaluate the influence of body composition, especially distribution of body fat, and insulin resistance on nonalcoholic fatty liver disease (NAFLD) in obese children. One hundred obese children (66 boys, 34 girls) with (n=60) and without NAFLD (n=40) were assessed. Anthropometry, laboratory tests, abdominal ultrasonography, and dual energy x-ray absorption metry (DXA) were evaluated in all subjects. Subject age and measurements of liver enzymes, γ- glutamyl transpeptidase (γGT), uric acid, high-density lipoprotein cholesterol, and insulin resistance were significantly different between the non-NAFLD group and NAFLD group. Body fat and trunk fat percentage were significantly different between the two groups (pfat percentage was not (p=0.683). Insulin resistance correlated significantly with body fat and trunk fat percentages, age, liver enzymes, γGT, and uric acid in obese children. Multiple logistic regression analysis indicated that insulin resistance and trunk fat percentage significantly affected the development of NAFLD in obese children. Body fat, especially abdominal fat, influences the development of insulin resistance and subsequent NAFLD in obese children. Therefore, body composition measurement using DXA, in conjunction with biochemical tests, may be beneficial in evaluating obese children with NAFLD.

  11. The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

    Science.gov (United States)

    Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

    2018-01-01

    The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

  12. Intestinal epithelial cell surface glycosylation in mice. I. Effect of high-protein diet.

    Science.gov (United States)

    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.

  13. The Impact of Hyperglycemic Emergencies on the Kidney and Liver

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    Feng Bai

    2013-01-01

    Full Text Available Studies on the alterations of liver and kidney function parameters in patients with diabetic ketoacidosis (DKA and diabetic ketosis (DK were limited. Participants with DKA, DK, non-DK, and healthy controls were enrolled in the current study. Parameters of liver and kidney function were measured and evaluated. The patients with DKA had higher levels of plasma glucose, hemoglobin A1c (HbA1c, uric acid, and creatinine but lower levels of transferases and protein compared with the other three groups ( for all. The patients with DK had higher levels of plasma glucose and HbA1c but lower levels of glutamyl transpeptidase and protein compared with the non-DK and control groups (. Prealbumin levels were significantly reduced in the severe DKA patients compared with the mild/moderate DKA patients. Serum prealbumin levels were correlated with albumin levels (, , HCO3 (, , and arterial pH (, in the DKA patients. A diagnostic analysis showed that lower prealbumin levels significantly reflected the presence of hyperglycemic emergencies (. Liver and kidney function parameters deteriorated, especially in DKA. Prealbumin levels can be of value in detecting the presence of hyperglycemic crisis. This clinical trial is registered with ChiCTR-OCH-12003077.

  14. Hemato-biochemical and pathological changes on avian influenza in naturally infected domestic ducks in Egypt

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    Essam A. Mahmoud

    2015-10-01

    Full Text Available Aim: Few studies have been made in regard to avian influenza (AI in ducks, thus the aim of this work was planned to investigate the hematological, biochemical, and pathological changes in domestic Egyptian ducks naturally infected with AI. Materials and Methods: 30 duck from private backyards 3-month-old 15 were clinically healthy (Group 1 and the other fifteen (Group 2 were naturally diseased with AI (H5N1. The disease was diagnosed by polymerase chain reaction as H5N1. Results: Duck showed cyanosis, subcutaneous edema of head and neck with nervous signs (torticollis. Hematological studies revealed a microcytic hypochromic anemia. Biochemical studies revealed a significant decrease in total protein, albumin and globulin concentration with significant increase of activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, Υ-glutamyl transpeptidase, lactic acid dehydrogenase and creatine phsphokinase. Prominent increase in creatinine and uric acid in addition to hypocalcemia and hyperphosphatemia were significantly detected in the infected ducks. Histopathological finding confirm these investigations. Conclusion: The highly pathogenic AIV (A/H5N1 became more severe infectious to ducks than before and causes nervous manifestations and blindness which were uncommon in ducks. Besides the significant increases of hepatic enzymes, brain, heart, and renal markers as a response to virus damage to these organs.

  15. Host differences in response to trickle infection with Fasciola gigantica in buffalo, Ongole and Bali calves.

    Science.gov (United States)

    Wiedosari, E; Hayakawa, H; Copeman, B

    2006-01-01

    Progressive weight gain, faecal egg counts, packed cell volume, percent eosinophils in blood, serum antibody and serum levels of glutamate dehydrogenase and gamma-glutamyl transpeptidase were recorded in seven swamp buffalo (Bubalis bubalis), 7 Ongole (Bos indicus) and four Bali calves (Bos sundiacus) which were infected orally with 15 metacercariae of Fasciola gigantica twice weekly for 32 weeks. Similar observations were made on four buffalo, 4 Ongole calves and 3 Bali calves maintained fluke-free as controls. Flukes were counted at slaughter 36 weeks after initial infection. Mean daily weight gains of infected Bali (228 +/- 100 (SD) g/day) and infected Ongole calves (328 +/- 57 (SD) g/day) were lower (p = 0.026 and 0.067, respectively) than those of control calves (405 +/- 107 (SD) g/day), but infected buffalo calves (379 +/- 78 (SD) g/day) had similar weight gains to those of the controls (p = 0.57). Throughout the trial, faecal Fasciola egg counts in buffaloes were about one-fifth of counts of Ongole calves, and counts in Bali calves were intermediate. Ongole calves had three times the number of flukes at slaughter in their liver compared to buffalo and Bali calves, which had similar numbers. However, there was evidence that Bali calves had acquired a degree of resistance about 24 weeks after infection commenced and may have lost adult flukes as a consequence.

  16. Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

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    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

    2008-11-15

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  17. Quantitative multivoxel 1H MR spectroscopy of the brain in children with acute liver failure

    International Nuclear Information System (INIS)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs; Lunsing, Roelineke J.; Spronsen, Francjan J. van; Verkade, Henkjan J.

    2008-01-01

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase). (orig.)

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

    Science.gov (United States)

    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.

  19. Atypical forms of acute Epstein-Barr virus infection in children

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    T.V. Sorokman

    2018-03-01

    Full Text Available Background. Today, there is a tendency to increase in Epstein-Barr virus infection (EBVI morbidity. The purpose of the study was to identify the incidence and features of atypical forms of acute EBVI in children. Material and methods. We have examined 28 children aged 6 months to 18 years with EBVI who were monitored in pediatric polyclinic. The activity of alanine aminotransferase and aspartate aminotransferase, levels of bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, markers of viral hepatitis were evaluated. Enzyme-linked immunosorbent assay was performed with determination of blood markers of EBV (immunoglobulin (Ig M viral capsid antigen (VCA, IgG early antigen, IgG VCA, avidity and cytomegalovirus (CMV (IgM, IgG, avidity, EBV deoxyribonucleic acid (DNA, CMV DNA; polymerase chain reaction was used for serological diagnosis. The data were processed by statistical analysis using Statistica 6 program. Results. In 71.4 % of cases, EBVI had usual course and moderate severity. The atypical forms of acute EBVI were observed in 28.5 % of cases. Clinically atypical forms began mainly from signs of acute respiratory infections followed by lesions of the internal organs (liver and heart, in particular, in children under 1 year of age, and changes in liver functional tests. Conclusions. The incidence of atypical forms of EBVI is 28.5 %. Atypical forms of EBVI are more common in infants and adolescents and associated with the damage to the internal organs (liver and heart.

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

    Science.gov (United States)

    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.

  1. To Analyze the Amelioration of Phenobarbital Induced Oxidative Stress by Erucin, as Indicated by Biochemical and Histological Alterations.

    Science.gov (United States)

    Arora, Rohit; Bhushan, Sakshi; Kumar, Rakesh; Mannan, Rahul; Kaur, Pardeep; Singh, Bikram; Sharma, Ritika; Vig, Adarsh Pal; Singh, Balbir; Singh, Amrit Pal; Arora, Saroj

    2016-01-01

    Phenobarbital is a commonly employed antidepressant and anti-epileptic drug. The cancer promoting activity of this genotoxic xenobiotic is often ignored. It is responsible for oxidative stress leading to modulation in xenobiotic and antioxidative enzymes. Glucosinolates and more specifically their hydrolytic products are known for their antioxidative and anticancer activities. The present study involves the analysis of hepatoprotective effect of erucin (isolated from Eruca sativa (Mill.) Thell.) against phenobarbital mediated hepatic damage in male wistar rats. The liver homogenate was analyzed for oxidative stress (superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase, glutathione reductase and lactate dehydrogenase), other oxidative parameters (thiobarbituric acid reactive species, conjugated dienes and lipid hydroperoxide), phase I enzymes (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P420, cytochrome P450 and cytochrome b5), phase II enzymes (γ-glutamyl transpeptidase, DT-diaphorase and glutathione-S-transferase), serum parameters (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin) and certain histological parameters. Erucin accorded protection from phenobarbital induced hepatic damage by normalizing antioxidative enzymes, other oxidative parameters, phase I, II, and serum parameters. Erucin, an analogue of sulforaphane has the potential to act as an anticancer agent by regulating various biochemical parameters.

  2. Induction by X-irradiation of adenosine triphosphatase-deficient islands in the rat liver and their characterization

    International Nuclear Information System (INIS)

    Kitagawa, T.; Nomura, K.; Sasaki, S.

    1985-01-01

    The potential of X-rays to induce preneoplastic lesions in the rat liver was studied in order to clarify the reason why X-rays are ineffective in inducing hepatocellular carcinoma in this animal. Male newborn rats at 8 or 22 days of age received whole body X-ray irradiation of 100 to 400 rads. After weaning they were fed either basal diet or a diet containing 0.05% phenobarbital as a promoter. X-rays induced numerous adenosine triphosphatase-deficient islands appearing in the liver by wk 22 of age. However, they were generally small, gamma-glutamyl transpeptidase-negative, and did not clearly respond to the promoting stimulus of phenobarbital. No hepatic tumors were observed by 22 mo after radiation, even in phenobarbital-treated animals. Thus, the X-ray-induced enzyme-altered islands differ somewhat qualitatively from those induced by potent hepatic carcinogens and their preneoplastic potential if at all present may be very low. Similarities between these X-ray-induced lesions and some types of spontaneous enzyme-altered islands are pointed out

  3. Using Blood Indexes to Predict Overweight Statuses: An Extreme Learning Machine-Based Approach.

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    Huiling Chen

    Full Text Available The number of the overweight people continues to rise across the world. Studies have shown that being overweight can increase health risks, such as high blood pressure, diabetes mellitus, coronary heart disease, and certain forms of cancer. Therefore, identifying the overweight status in people is critical to prevent and decrease health risks. This study explores a new technique that uses blood and biochemical measurements to recognize the overweight condition. A new machine learning technique, an extreme learning machine, was developed to accurately detect the overweight status from a pool of 225 overweight and 251 healthy subjects. The group included 179 males and 297 females. The detection method was rigorously evaluated against the real-life dataset for accuracy, sensitivity, specificity, and AUC (area under the receiver operating characteristic (ROC curve criterion. Additionally, the feature selection was investigated to identify correlating factors for the overweight status. The results demonstrate that there are significant differences in blood and biochemical indexes between healthy and overweight people (p-value < 0.01. According to the feature selection, the most important correlated indexes are creatinine, hemoglobin, hematokrit, uric Acid, red blood cells, high density lipoprotein, alanine transaminase, triglyceride, and γ-glutamyl transpeptidase. These are consistent with the results of Spearman test analysis. The proposed method holds promise as a new, accurate method for identifying the overweight status in subjects.

  4. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics.

    Science.gov (United States)

    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.

  5. Formulation for Effective Screening and Management of Nonalcoholic Steatohepatitis: Noninvasive NAFLD Management Strategy

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    Kanae Hirose

    2016-01-01

    Full Text Available To establish a versatile means for screening and management of nonalcoholic steatohepatitis (NASH, shear wave velocity was measured in 20 normal controls and 138 consecutive nonalcoholic fatty liver disease (NAFLD cases. Referencing biochemical properties in 679 healthy volunteers, a formula to distinguish NASH suspects was established and validated in another cohort of 138 histologically proven NAFLD cases. NASH and simple steatosis (SS suspects were selected based on a plot of shear wave velocity against age. A formula consisting of five factors (γ-glutamyl transpeptidase, alkaline phosphatase, platelet counts, body mass index, and presence/absence of type 2 diabetes mellitus distinguished NASH suspects from SS suspects with area under the receiver operating characteristic curve values of 86% and 84% in the development and validation cohorts. Among 25 NAFLD cases in which shear wave velocity was repeatedly measured, 8 and 9 cases revealed an increase or decrease, respectively, of shear wave velocity in the entire liver, and the corresponding change in shear wave velocity was primarily observed in the right lobe or the left lateral segment, respectively. These results suggest that the new formula and sequential shear wave velocity measurements at each segment enable high throughput screening of NASH suspects and noninvasive assessment of pathophysiological alleviation/aggravation in cases of NASH.

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

    Science.gov (United States)

    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.

  7. Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver

    International Nuclear Information System (INIS)

    Jiménez-García, Mónica Noemí; Arellanes-Robledo, Jaime; Aparicio-Bautista, Diana Ivette; Rodríguez-Segura, Miguel Ángel; Villa-Treviño, Saúl; Godina-Nava, Juan José

    2010-01-01

    Recently, extremely low frequency electromagnetic fields (ELF-EMF) have been studied with great interest due to their possible effects on human health. In this study, we evaluated the effect of 4.5 mT - 120 Hz ELF-EMF on the development of preneoplastic lesions in experimental hepatocarcinogenesis. Male Fischer-344 rats were subjected to the modified resistant hepatocyte model and were exposed to 4.5 mT - 120 Hz ELF-EMF. The effects of the ELF-EMF on hepatocarcinogenesis, apoptosis, proliferation and cell cycle progression were evaluated by histochemical, TUNEL assay, caspase 3 levels, immunohistochemical and western blot analyses. The application of the ELF-EMF resulted in a decrease of more than 50% of the number and the area of γ-glutamyl transpeptidase-positive preneoplastic lesions (P = 0.01 and P = 0.03, respectively) and glutathione S-transferase placental expression (P = 0.01). The number of TUNEL-positive cells and the cleaved caspase 3 levels were unaffected; however, the proliferating cell nuclear antigen, Ki-67, and cyclin D1 expression decreased significantly (P ≤ 0.03), as compared to the sham-exposure group. The application of 4.5 mT - 120 Hz ELF-EMF inhibits preneoplastic lesions chemically induced in the rat liver through the reduction of cell proliferation, without altering the apoptosis process

  8. Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver

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    Villa-Treviño Saúl

    2010-04-01

    Full Text Available Abstract Background Recently, extremely low frequency electromagnetic fields (ELF-EMF have been studied with great interest due to their possible effects on human health. In this study, we evaluated the effect of 4.5 mT - 120 Hz ELF-EMF on the development of preneoplastic lesions in experimental hepatocarcinogenesis. Methods Male Fischer-344 rats were subjected to the modified resistant hepatocyte model and were exposed to 4.5 mT - 120 Hz ELF-EMF. The effects of the ELF-EMF on hepatocarcinogenesis, apoptosis, proliferation and cell cycle progression were evaluated by histochemical, TUNEL assay, caspase 3 levels, immunohistochemical and western blot analyses. Results The application of the ELF-EMF resulted in a decrease of more than 50% of the number and the area of γ-glutamyl transpeptidase-positive preneoplastic lesions (P = 0.01 and P = 0.03, respectively and glutathione S-transferase placental expression (P = 0.01. The number of TUNEL-positive cells and the cleaved caspase 3 levels were unaffected; however, the proliferating cell nuclear antigen, Ki-67, and cyclin D1 expression decreased significantly (P ≤ 0.03, as compared to the sham-exposure group. Conclusion The application of 4.5 mT - 120 Hz ELF-EMF inhibits preneoplastic lesions chemically induced in the rat liver through the reduction of cell proliferation, without altering the apoptosis process.

  9. 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).

    Science.gov (United States)

    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

  10. The Hepatoprotective Effect of Vitamin A against Gasoline Vapor Toxicity in Rats.

    Science.gov (United States)

    Uboh, Friday E; Ekaidem, Itemobong S; Ebong, Patrick E; Umoh, Ime B

    2009-06-01

    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 cm 3 h -1 m -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. 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. The results obtained from this study showed that exposure to gasoline vapors caused significant increase (P produced a significant decrease (P 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.

  11. Evaluation of the protective effect of garlic oil on hepatic injury induced by pesticides

    International Nuclear Information System (INIS)

    Afifi, E.A.; El-Sherbiny, E.M.; Tawfik, S.M.F.

    2006-01-01

    The present study was directed to evaluate the effect of repeated daily oral administrations of two pesticides; malathion (organophosphorus) and lannate (carbamate) at dose levels of 27.5 and 3.4 mg/kg body weight, respectively. Garlic oil at a dose of 0.2 ml/kg body weight was given by gavage during pesticides treatment (garlic oil + pesticides) to evaluate its role against the harmful effects of the two selected pesticides in male albino rats. The level of serum 14 C-isoleucine (4 μCi/100 g body weight) twenty-four hours post administration of malathion or lannate and also garlic oil was studied. Malathion and lannate treatments resulted in significant increase in the activity of alkaline phosphatase, acid phosphatase, gamma glutamyl transferase (GGT), bilirubin, 5-nucleotidase, glucose-6-phosphatase and serum total calcium level. On the other hand, pesticides treatment caused significant decrease in serum inorganic phosphorus. The level of serum 14 C-isoleucine twenty-four hours post administration of malathion or lannate and also garlic oil was significantly increased due to pesticides treatment and decreased in case of garlic oil treatment. The protective role of garlic oil was clear to some extent and could ameliorate the activities of some serum enzymes in addition to inorganic phosphorus. The administration of garlic oil to malathion treated animals was more effective in ameliorating the disturbed levels in case of malathion than that occurred with lannate pesticide treatment

  12. Growth and Blood Parameters of Weaned Crossbred Beef Calves Fed Forage Kale (Brassica oleracea spp. acephala

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    Y. Chorfi

    2015-01-01

    Full Text Available Forty lightweight calves (206.4±3.2 kg were randomly distributed to four treatments: (Control low nutritive value pasture and hay plus 1 kg d−1 of rolled barley; (Pasture management intensive pasture; (Haylage timothy haylage; and (Kale 50% timothy haylage −50% kale pasture. Blood samples were analysed for thyroid hormones, liver enzymes, glucose, cholesterol, total proteins (TP, albumin, globulins, and urea-N. At the end of the trial, the Pasture group was the heaviest with 323.6±4.2 kg BW and 1.54 kg ADG. Final BW and ADG were similar for the Kale and Haylage groups. Blood T3 was higher for Kale than for the other groups. The T3/T4 ratio was greater for Control at the end of the experiment. There were no treatment differences for T4, aspartate aminotransferase (AST, gamma glutamyl transferase (GGT, glutamate dehydrogenase (GLDH, cholesterol, and glucose. Blood urea-N was lower for Kale and higher for Pasture; however albumin concentrations were greater for Pasture and similar for other treatments. Except for the Control group, calves had a lower concentration of circulating globulins at the end than at the beginning of the experiment. This study showed that Kale could be fed to backgrounding calves without detrimental effects on performance.

  13. Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

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    Abdel-Tawab H. Mossa

    2015-01-01

    Full Text Available 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.

  14. Blood serum components and serum protein test of Hybro-PG broilers of different ages

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    PRL Silva

    2007-12-01

    Full Text Available Blood serum samples of HYBRO PG broilers were analyzed, with 30 samples collected from 21-day-old broilers (G1, 30 from 35-day-old birds (G2, and 30 from 42-day-old birds (G3, with the aim of establishing normal values of some blood serum parameters. The activities of the enzymes gamma-glutamyl-transferase (GGT, aspartate aminotransferase (AST, creatine kinase (CK, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH, serum levels of total calcium, calcium ion, phosphorus, sodium, potassium, magnesium, chlorides, creatinine, uric acid, triglycerides, cholesterol, total protein, albumin, total and indirect and direct bilirubin, and electrophoretic profile of serum proteins in acrylamide (SDS-PAGE and agarose gel were determined. There was no influence of age on total bilirubin and albumin levels. All the other evaluated parameters presented differences in at least one age group. Protein electrophoretic profile also changed as a function of age. The obtained results can be considered as normal for the studied ages, and therefore be used as references for the interpretation of laboratory exams of broilers of this genetic line in the evaluated ages.

  15. Effects of age and sex on blood biochemistry of dorper lambs

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    Rebecca Espírito Santo da Cruz

    2017-10-01

    Full Text Available The purpose of this study was to evaluate the physiological variations and influence of age group and sex on biochemical variables of 32 male and female Dorper sheep at the age of 15 to 121 days. Four blood samples were collected from each animal, at monthly intervals, totaling 128 samples. Biochemical variables determined in each sample were total protein (TP, albumin (ALB, globulin (GLB, albumin/globulin ratio (A/G, glucose (GLU, triglycerides (TG, total cholesterol (tCHOL, high density cholesterol carrying lipoproteins (HDL-C, low density cholesterol carrying lipoproteins (LDL-C, very low density cholesterol carrying lipoproteins (VLDL-C, urea, creatinine (CRE, total calcium (tCa, ionized calcium (iCa, phosphorus (P, calcium/phosphorus ratio (Ca/P, magnesium (Mg, sodium (Na, potassium (K, chloride (Cl, alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyl transferase (GGT and alkaline phosphatase (ALP. The results were obtained in four moments according to age: M1 - sheep from 15 to 30 days, M2 - sheep from 45 to 61 days, M3 - sheep from 74 to 90 days and M4 - sheep from 105 to 121 days. Comparing the values of the biochemical variables among the four age groups studied a significant difference (p 0.05 the values of the biochemical variables analyzed. Based on the results, it is concluded that the age groups exert a significant influence on the majority of blood biochemical variables of Dorper sheep from 15 to 121 days of age.

  16. Quality specifications for the extra-analytical phase of laboratory testing: Reference intervals and decision limits.

    Science.gov (United States)

    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.

  17. Influence of Fasciola Hepatica on Serum Biochemical Parameters and Vascular and Biliary System of Sheep Liver

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    A Hodžić

    2013-03-01

    Full Text Available 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.

  18. Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa

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    Judyta K. Juranek

    2010-09-01

    Full Text Available The aim of our project was to study the effect of streptozotocin (STZ—induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products, and its ligands—S100B and Carboxymethyl Lysine (CML-advanced glycation endproduct (AGE in the laboratory pig. Six months after STZ—injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products—methyl-glyoxal (MG were performed. The results of our study revealed that STZ—injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy.

  19. Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa

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    Judyta K. Juranek

    2010-01-01

    Full Text Available The aim of our project was to study the effect of streptozotocin (STZ–-induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products, and its ligands–-S100B and Carboxymethyl Lysine (CML-advanced glycation endproduct (AGE in the laboratory pig. Six months after STZ–-injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products–-methylglyoxal (MG were performed. The results of our study revealed that STZ–-injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy.

  20. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

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    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  1. The Antitumor Activity of the Novel Compound Jesridonin on Human Esophageal Carcinoma Cells.

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    Cong Wang

    Full Text Available Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP, alanine transaminase (ALT, aspartate transaminase (AST, gamma-glutamyl transferase (GGT, total protein (TP and albumin (ALB indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.

  2. Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress.

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    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal Padmanabhan

    2004-08-20

    Alcoholic liver disease is a major medical complication of alcohol abuse and a common liver disease in western countries. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in the development of alcoholic liver disease. Alcohol alone or in combination with high fat is known to cause oxidative injury. The present study therefore aims at evaluating the protective role of curcumin, an active principle of turmeric and a synthetic analog of curcumin (CA) on alcohol and thermally oxidised sunflower oil (DeltaPUFA) induced oxidative stress. Male albino Wistar rats were used for the experimental study. The liver marker enzymes: gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), the lipid peroxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) and antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were used as biomarkers for testing the antioxidant potential of the drugs. The liver marker enzymes and lipid peroxidative indices were increased significantly in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups. Administration of curcumin and CA abrograted this effect. The antioxidant status which was decreased in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups was effectively modulated by both curcumin and CA treatment. However, the reduction in oxidative stress was more pronounced in CA treatment groups compared to curcumin. In conclusion, these observations show that CA exerts its protective effect by decreasing the lipid peroxidation and improving antioxidant status, thus proving itself as an effective antioxidant.

  3. Possible Protective Effect of Kombucha Tea Ferment on Carbon Tetrachloride Induced Liver Damage in Irradiated Rats

    International Nuclear Information System (INIS)

    Gharib, O.A.; Fahim, Th.M.

    2008-01-01

    This study has shown that administration of kombucha ferment tea (KT) to rats improved the damage caused in livers of animals treated with toxic chemicals such as carbon tetrachloride (CCL 4 ) and/ or exposed to y-irradiation. This work was undertaken to evaluate the possible protective effects of treatment with KT ferment in rat liver after a long-term treatment with CCL 4 alone and with subsequent y-irradiation. Hepatic pathological changes observed in the CCL 4 -treated rats included increased serum alanine transaminase (ALT) , aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) activities as well as concentration of bilirubin in addition to a decrease in the concentration of serum albumin and total antioxidant capacity (TAC). Consistent with these changes, the increase in oxidative stress markers expressed as malondialdehyde (MDA) concentration and depletion in glutathione (GSH) contents in liver was observed. 24 h after the last dose of KT administration in a group of animals treated with CCL 4 and/ or radiation exposure cessation, the pathological changes were recovered. These results demonstrate that most of the pathological alterations in the liver in response to CCL 4 and/ or radiation exposure intoxication are recoverable upon treatment with KT ferments

  4. d-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats.

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    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.

  5. Hematology, plasma biochemistry, and tissue enzyme activities of invasive red lionfish captured off North Carolina, USA.

    Science.gov (United States)

    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.

  6. Effect of long term intake of aspartame on antioxidant defense status in liver.

    Science.gov (United States)

    Abhilash, M; Paul, M V Sauganth; Varghese, Mathews V; Nair, R Harikumaran

    2011-06-01

    The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats, weighing 150-175 g, were randomly divided into three groups as follows: first group was given aspartame dissolved in water in a dose of 500 mg/kg b.wt.; the second group was given a dose of 1000 mg/kg b.wt.; and controls were given water freely. Rats that had received aspartame (1000 mg/kg b.wt.) in the drinking water for 180 days showed a significant increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of rats that had received aspartame (1000 mg/kg b.wt.). Glutathione was significantly decreased in both the experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-treated rats (1000 mg/kg b.wt.). It can be concluded from these observations that long term consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status mainly through glutathione dependent system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Evaluation of circulating zonulin as a potential marker in the pathogenesis of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Hendy, Olfat M; Elsabaawy, Maha M; Aref, Mona M; Khalaf, Fatma M; Oda, Abdel Moaty A; El Shazly, Helmy M

    2017-07-01

    Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested. Liver function tests, serum glucose, fasting insulin, C peptide, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), IL-6, and circulating zonulin were performed to all subjects. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), triglycerides, HDL-c, fasting insulin, C peptide, HOMA-IR, IL-6, and serum zonulin were higher in NAFLD group than in controls (p Zonulin was positively correlated with body mass index (BMI), ALT, triglycerides, fasting insulin, HOMA-IR, liver histopathology, and serum IL-6 (p zonulin was found to be of diagnostic value of NASH occurrence with 100% sensitivity and specificity (AUR = 1.000, p-value = zonulin levels in NAFLD patients with steep rise in NASH group denotes a possible role in pathogenesis of NAFLD occurrence and progression. This could open a new avenue of implicating zonulin antagonists as targeted therapies in NAFLD prevention. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  8. Chemical composition and biological evaluation of Physalis peruviana root as hepato-renal protective agent.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. In vitro Effects of Four Native Brazilian Medicinal Plants in CYP3A4 mRNA Gene Expression, Glutathione Levels, and P-Glycoprotein Activity.

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    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 effect upon hPXR (EC50 = 0.38 mg/mL). Total intracellular glutathione levels were significantly depleted by exposure to Solanum paniculatum (-44%, p Cordia verbenacea (-47%, p activity (-48%, p active pharmacovigilance is recommended for the other three species, especially in the case of Solanum paniculatum.

  11. Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

    Science.gov (United States)

    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

  12. Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function.

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    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.

  13. Serologic response in bottlenose dolphins Tursiops truncatus infected with Brucella sp. using a dolphin-specific indirect ELISA.

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    Meegan, Jenny; Dunn, J Lawrence; Venn-Watson, Stephanie K; Smith, Cynthia R; Sidor, Inga; Jensen, Eric D; Van Bonn, William G; Pugh, Roberta; Ficht, Thomas; Adams, L Garry; Nielsen, Klaus; Romano, Tracy A

    2012-12-03

    Marine-origin Brucella infections and serologic evidence of exposure have been documented in multiple cetacean species. A dolphin-specific indirect enzyme-linked immunosorbent assay (ELISA) was developed to screen bottlenose dolphin sera for anti-Brucella antibodies. A total of 131 serum samples collected over a 2 to 18 yr period from 6 bottlenose dolphins Tursiops truncatus with confirmed Brucella infections were analyzed for the presence and magnitude of antibody titers against marine-origin Brucella to compare individual antibody responses to various disease manifestations. Additionally, an epidemiologic serologic survey of a managed population of 64 bottlenose dolphins was performed to evaluate for the presence of antibodies and to determine whether there were any clinical pathology predictors for exposure or infection. The serologic results revealed that the dolphins with Brucella-associated abortions were seronegative for 7 to 18 yr until after the abortion and maintained positive titers for several years, with 2 of 3 animals returning to seronegative status. In contrast, the dolphins with Brucella-associated pulmonary or bone lesions maintained persistent positive titers for 2 to 18 yr. The population serosurvey revealed no significant differences in antibody levels among males and females, and dolphins between the ages of 17 and 25 yr were 6.8 times more likely to be Brucella antibody positive compared to those that were younger or older. Seropositive dolphins did not have significant inflammation compared to seronegative dolphins but were more likely to have higher levels of aspartate aminotransferase and gamma-glutamyl transpeptidase. Among 16 dolphins that tested seropositive, 13 (81.3%) had previously been seropositive for at least 3 to 5 yr.

  14. Correlation between liver function tests and metabolic syndrome in hepatitis-free elderly

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    Hung-Sheng Shang

    2015-01-01

    Full Text Available Background: We aimed to investigate the relationship between liver function tests (LFTs and metabolic syndrome (MetS as several studies have shown positive correlations between some of the LFTs, including alanine aminotransferase (ALT and γ-glutamyl transpeptidase (γ-GT, and MetS but have not fully explored the same in the elderly. Owing to the progress in public health, the aging of the general population becomes a major issue. Design: We enrolled subjects aged over 60 years who underwent routine health checkups in a Health Screening Center after excluding subjects with a history of hepatitis B or C infection, excessive alcohol consumption, liver fibrosis, cirrhosis, acute hepatitis, diabetes, hypertension, dyslipidemia, cardiovascular disease, or receiving medications for these diseases. Finally, 9,282 participants were eligible for analysis. Statistical Analysis: All data were tested for normal distribution with the Kolmogorov-Smirnov test and for homogeneity of variances with the Levene′s test. A t-test was used to evaluate the differences between the two groups. Univariate and multivariate regressions were used to observe correlations between different parameters. Receiver operating characteristic curves of each LFT were used to predict MetS. Areas under curves and 95% confidence interval were also estimated and compared. Results: With the exception of aspartate aminotransferase and α-fetal protein, the results of LFTs, including total and direct bilirubin, alkaline phosphatase (ALP, ALT, and γ-GT, were altered in the group with MetS. Furthermore, the levels of γ-GT in men and ALP in women were independently associated with all MetS components and had the highest areas under receiver operating characteristic curves. Conclusion: Abnormal LFTs are highly correlated with MetS in the hepatitis-free elderly, with levels of γ-GT in men and ALP in women being the most important factors. LFTs may represent an auxiliary tool for the

  15. Possible Protective Effect of Aqueous Extract of Moringa oleifera Lam. on Gamma Radiation Induced-Oxidative Stress in Rats

    International Nuclear Information System (INIS)

    Abd El-Azime, A.Sh.; Kamal El-Dein, E.M.

    2014-01-01

    Medicinal herbs are used in indigenous system of medicine for various diseases. Moringa oleifera (M. oleifera) has a high medicinal value which has been recognized. The present study was designed to evaluate the protective effect of aqueous extract of M. oleifera leaves against whole body gamma radiation-induced toxicity in rats. Rats received orally by gavage the aqueous extract of M. oleifera leaves 300 mg/Kg body weight/day for 40 days and rats subjected to whole body gamma-irradiation at a dose of 5 Gy delivered as single exposure dose at day 35 of M. oleifera treatment rats and sacrificed at 5th day after irradiation. The results obtained showed that exposure to gamma radiation provoked a significant increase in serum gamma-glutamyl transpeptidase (γ-GT), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP), glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (vLDL-C) level. While high density lipoprotein cholesterol (HDL-C) and insulin level showed a significant decrease. Moreover a significant decrease of glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities associated to a significant increase of thiobarbituric acid reactive substances (TBARS) were recorded in blood and liver of rats. Treatment with M. oleifera significantly reduced the radiation-induced serum and liver biochemical disorders which was associated with a significant amelioration in antioxidant status in both liver and serum. The results indicated that M. oleifera might protect from radiation induced damage due to its ability to scavenge free radicals

  16. Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

    Science.gov (United States)

    Kawanaka, Miwa; Nishino, Ken; Oka, Takahito; Urata, Noriyo; Nakamura, Jun; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Chiba, Yasutaka; Yamada, Gotaro

    2015-01-01

    Objective Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. PMID:26082668

  17. Impact of Liver Indicators on Clinical Outcome in Patients Undergoing Transcatheter Aortic Valve Implantation.

    Science.gov (United States)

    Wendt, Daniel; Kahlert, Philipp; Canbay, Ali; Knipp, Stephan; Thoenes, Martin; Cremer, Gordina; Al-Rashid, Fadi; Jánosi, Rolf-Alexander; El-Chilali, Karim; Kamler, Markus; El Gabry, Mohamed; Marx, Philipp; Dohle, Daniel Sebastian; Tsagakis, Konstantinos; Benedik, Jaroslav; Gerken, Guido; Rassaf, Tienush; Jakob, Heinz; Thielmann, Matthias

    2017-10-01

    Liver dysfunction increases death and morbidity after cardiac operations. There are currently no data evaluating liver function in patients undergoing transcatheter aortic valve replacement (TAVR). We aimed therefore to evaluate our TAVR results in regard to liver function. A total of 640 consecutive TAVR patients were evaluated. Of those, 11 patients presented with chronic liver disease before TAVR. The Model for End-Stage Liver Disease score was used to measure liver function in these patients. The primary study end point was 30-day mortality in patients presenting with liver dysfunction. Secondary study end point was liver enzymes after TAVR. The mean Model for End-Stage Liver Disease score in patients with chronic liver disease was 16.8 ± 6.2 (median, 18; range, 7 to 26). The 30-day mortality was 9.1% (57 of 629) in patients presenting without liver disease and 9.1% (1 of 11) in patients with liver disease (p = 1.00). Patients with chronic liver disease showed significantly higher preoperative levels of γ-glutamyl transpeptidase (p < 0.001). After TAVR, we observed a significant increase in alanine aminotransferase on postoperative day 3 compared with preoperative values (p < 0.001), accompanied by a decrease in albumin (p < 0.001). Liver cirrhosis per se is not considered as a contraindication for cardiac operations. In the present study, we did not observe a higher 30-day mortality rate in liver cirrhotic patients undergoing TAVR, suggesting TAVR as a feasible alternative with acceptable outcomes in patients with chronic liver disease. Moreover, the present study is the first to evaluate liver variables in patients undergoing TAVR. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Evaluation of diffuse hepatic diseases by integrated image, SPECT and numerical taxonomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Shin

    1987-02-01

    In 135 patients with various hepatic diseases, cardiopulmonary circulation and hepatic accumulation of the activity were collected for 100 sec after bolus injection of 111-222 MBq (3 - 6 mci) of /sup 99m/Tc-phytate, and then integrated as a single image. Anterior, right lateral and posterior planar images, and hepatosplenic SPECT images were obtained thereafter. Lung to liver count ratio (P/L) was estimated by the integrated image. Liver volume (HV), spleen volume (SV) and liver to spleen count ratio (MHC/MSC) were calculated using the data obtained by SPECT. P/L was useful as an index of effective hepatic blood flow. MHC/MSC was closely correlated with the grade of portal hypertension. HV or SV alone shows low clinical value in discriminating liver diseases. Principal component analysis was applied to the 4 above-mentioned radinuclide data and the following 11 laboratory data ; total serum protein, serum albumine, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactic dehydrogenase (LDH), alkaline phosphatase (AL-P), zink sulfateturbidity test (ZTT), thymol turbidity test (TTT), r-glutamyl transpeptidase (r-GTP), cholinesterase (Ch-E), and total bilirubin (T-Bil). These fifteen data were condensed to 5 principal components. And then cluster analysis was carried out among 135 patients. The subjects were classified in 7 small groups. In group (G) I to GIII, frequency of liver cirrhosis was high, while on the contrary in GIV to GVII, the frequency of normal cases increased gradually. From the above results, cluster analysis seemed to reflect the pathophysiological state and the grade of the disease. This method might be useful for estimation of the grade of damage in diffuse hepatic disease and a good objective evaluation method in follow-up studies. (J.P.N.).

  19. Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study.

    Science.gov (United States)

    Alkerwi, Ala'a; Sauvageot, Nicolas; Crichton, Georgina E; Elias, Merrill F; Stranges, Saverio

    2016-05-01

    This study examined the association of chocolate consumption with insulin resistance and serum liver enzymes in a national sample of adults in Luxembourg. A random sample of 1153 individuals, aged 18-69 years, was recruited to participate in the cross-sectional Observation of Cardiovascular Risk Factors in Luxembourg study. Chocolate consumption (g/d) was obtained from a semi-quantitative FFQ. Blood glucose and insulin levels were used for the homoeostasis model assessment of insulin resistance (HOMA-IR). Hepatic biomarkers such as serum γ-glutamyl-transpeptidase (γ-GT), serum aspartate transaminase and serum alanine transaminase (ALT) (mg/l) were assessed using standard laboratory assays. Chocolate consumers (81·8 %) were more likely to be younger, physically active, affluent people with higher education levels and fewer chronic co-morbidities. After excluding subjects taking antidiabetic medications, higher chocolate consumption was associated with lower HOMA-IR (β=-0·16, P=0·004), serum insulin levels (β=-0·16, P=0·003) and γ-GT (β=-0·12, P=0·009) and ALT (β=-0·09, P=0·004), after adjustment for age, sex, education, lifestyle and dietary confounding factors, including intakes of fruits and vegetables, alcohol, polyphenol-rich coffee and tea. This study reports an independent inverse relationship between daily chocolate consumption and levels of insulin, HOMA-IR and liver enzymes in adults, suggesting that chocolate consumption may improve liver enzymes and protect against insulin resistance, a well-established risk factor for cardiometabolic disorders. Further observational prospective research and well-designed randomised-controlled studies are needed to confirm this cross-sectional relationship and to comprehend the role and mechanisms that different types of chocolate may play in insulin resistance and cardiometabolic disorders.

  20. Renal involvement in dogs with babesiosis

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2001-07-01

    Full Text Available Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium, fractional clearance of sodium (FcNa and potassium (FcK, urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n =10 and 3 groups of babesiosis cases were studied: mild uncomplicated (n =10, severe uncomplicated (n = 11, and complicated (n = 9. All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serumelectrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant

  1. Characterization of toxicosis in sheep dosed with blossoms of sacahuiste (Nolina microcarpa).

    Science.gov (United States)

    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.

  2. Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Radu M. Nanau

    2015-06-01

    Full Text Available Background: The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. Methods: A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010–2015. The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Findings: Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

  3. Concurrent low brain and high liver uptake on FDG PET are associated with cardiovascular risk factors

    International Nuclear Information System (INIS)

    Nam, Hyun Yeol; Jun, Sung Min; Pak, Kyoung June; Kim, In Joo

    2017-01-01

    Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without

  4. Rib fractures in chronic alcoholic men: Relationship with feeding habits, social problems, malnutrition, bone alterations, and liver dysfunction.

    Science.gov (United States)

    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. A thin-layer liquid culture technique for the growth of Helicobacter pylori.

    Science.gov (United States)

    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.

  6. Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects

    Science.gov (United States)

    Kikuchi, Masahiro; Ushida, Yusuke; Shiozawa, Hirokazu; Umeda, Rumiko; Tsuruya, Kota; Aoki, Yudai; Suganuma, Hiroyuki; Nishizaki, Yasuhiro

    2015-01-01

    AIM: To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants. METHODS: In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme. RESULTS: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers, ALT [median (interquartile range), before: 54.0 (34.5-79.0) vs after supplementation: 48.5 (33.3-65.3) IU/L, P NDMA-induced chronic liver failure in rats, which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST (86.6 ± 95.2 vs 107.8 ± 7.7 IU/g, P < 0.01). CONCLUSION: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress. PMID:26604653

  7. Immobilized enzyme reactor chromatography: Optimization of protein retention and enzyme activity in monolithic silica stationary phases

    International Nuclear Information System (INIS)

    Besanger, Travis R.; Hodgson, Richard J.; Green, James R.A.; Brennan, John D.

    2006-01-01

    Our group recently reported on the application of protein-doped monolithic silica columns for immobilized enzyme reactor chromatography, which allowed screening of enzyme inhibitors present in mixtures using mass spectrometry for detection. The enzyme was immobilized by entrapment within a bimodal meso/macroporous silica material prepared by a biocompatible sol-gel processing route. While such columns proved to be useful for applications such as screening of protein-ligand interactions, significant amounts of entrapped proteins leached from the columns owing to the high proportion of macropores within the materials. Herein, we describe a detailed study of factors affecting the morphology of protein-doped bioaffinity columns and demonstrate that specific pH values and concentrations of poly(ethylene glycol) can be used to prepare essentially mesoporous columns that retain over 80% of initially loaded enzyme in an active and accessible form and yet still retain sufficient porosity to allow pressure-driven flow in the low μL/min range. Using the enzyme γ-glutamyl transpeptidase (γ-GT), we further evaluated the catalytic constants of the enzyme entrapped in capillary columns with different silica morphologies as a function of flowrate and backpressure using the enzyme reactor assay mode. It was found that the apparent activity of the enzyme was highest in mesoporous columns that retained high levels of enzyme. In such columns, enzyme activity increased by ∼2-fold with increases in both flowrate (from 250 to 1000 nL/min) and backpressure generated (from 500 to 2100 psi) during the chromatographic activity assay owing to increases in k cat and decreases in K M , switching from diffusion controlled to reaction controlled conditions at ca. 2000 psi. These results suggest that columns with minimal macropore volumes (<5%) are advantageous for the entrapment of soluble proteins for bioaffinity and bioreactor chromatography

  8. Associations between liver 18F fluoro-2-deoxy-D-glucose accumulation and various clinical parameters in a Japanese population. Influence of the metabolic syndrome

    International Nuclear Information System (INIS)

    Kamimura, Kiyohisa; Nagamachi, Shigeki; Wakamatsu, Hideyuki

    2010-01-01

    Liver demonstrates a heterogeneous 18 F fluoro-2-deoxy-D-glucose ( 18 F-FDG) uptake pattern and sometimes shows an abnormally increased uptake even when there is no malignant tissue. The aim of this study was to evaluate the relationships of liver 18 F-FDG uptake as related to physical factors, fatty liver, blood glucose (BG), and other biochemical data. 18 F-FDG positron emission tomography (PET) imaging was performed in 101 consecutive subjects for cancer screening. Multiple stepwise regression analysis was used to define the best predictors of the liver standardized uptake value (SUV) among height, weight, waist circumference, body mass index (BMI), systolic and diastolic blood pressure, BG and other biochemical data, id est (i.e.), aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, total protein, total bilirubin, and alkaline phosphatase. Furthermore, we evaluated the association between liver 18 F-FDG uptake and the metabolic syndrome. The independent factors for increased liver 18 F-FDG uptake (mean SUV >=2) were BMI (P 18 F-FDG uptake. In addition, the liver 18 F-FDG uptake of metabolic syndrome subjects was significantly higher than that of a non-metabolic syndrome subjects. BMI was the strongest determinant of liver 18 F-FDG uptake, and the liver 18 F-FDG uptake of metabolic syndrome subjects was significantly higher than that of non-metabolic syndrome subjects. This result suggests that a subject with a high liver 18 F-FDG uptake should be screened for the metabolic syndrome. (author)

  9. The use of urinary and kidney SILAM proteomics to monitor kidney response to high dose morpholino oligonucleotides in the mdx mouse

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    Aiping Zhang

    2015-01-01

    Full Text Available Phosphorodiamidate morpholino oligonucleotides (PMO are used as a promising exon-skipping gene therapy for Duchenne muscular dystrophy (DMD. One potential complication of high dose PMO therapy is its transient accumulation in the kidneys. Therefore new urinary biomarkers are needed to monitor this treatment. Here, we carried out a pilot proteomic profiling study using stable isotope labeling in mammals (SILAM strategy to identify new biomarkers to monitor the effect of PMO on the kidneys of the dystrophin deficient mouse model for DMD (mdx-23. We first assessed the baseline renal status of the mdx-23 mouse compared to the wild type (C57BL10 mouse, and then followed the renal outcome of mdx-23 mouse treated with a single high dose intravenous PMO injection (800 mg/kg. Surprisingly, untreated mdx-23 mice showed evidence of renal injury at baseline, which was manifested by albuminuria, increased urine output, and changes in established urinary biomarker of acute kidney injury (AKI. The PMO treatment induced further transient renal injury, which peaked at 7 days, and returned to almost the baseline status at 30 days post-treatment. In the kidney, the SILAM approach followed by western blot validation identified changes in Meprin A subunit alpha at day 2, then returned to normal levels at days 7 and 30 after PMO injection. In the urine, SILAM approach identified an increase in Clusterin and γ-glutamyl transpeptidase 1 as potential candidates to monitor the transient renal accumulation of PMO. These results, which were confirmed by Western blots or ELISA, demonstrate the value of the SILAM approach to identify new candidate biomarkers of renal injury in mdx-23 mice treated with high dose PMO.

  10. Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Kawanaka M

    2015-06-01

    Full Text Available Miwa Kawanaka,1 Ken Nishino,1 Takahito Oka,1 Noriyo Urata,1 Jun Nakamura,1 Mitsuhiko Suehiro,1 Hirofumi Kawamoto,1 Yasutaka Chiba,2 Gotaro Yamada1 1Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan; 2Clinical Research Center, Kinki University Hospital, Sayama, Japan Objective: Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH. Methods: In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA, tyrosine (Tyr, and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index, biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin, and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid. Results: Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion: Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels

  11. Construction of multiple linear regression models using blood biomarkers for selecting against abdominal fat traits in broilers.

    Science.gov (United States)

    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 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.

  12. Methyl mercury uptake across bovine brain capillary endothelial cells in vitro: The role of amino acids

    International Nuclear Information System (INIS)

    Aschner, M.; Clarkson, T.W.

    1989-01-01

    Previous studies in the rat in vivo have demonstrated that co-injection of methyl mercury (MeHg) with L-cysteine into the common carotid artery enhances brain Hg levels folowing a single capillary pass through the CNS vasculature. In order to elucidate the relationship between MeHg transport and the neutral amino acid transport carrier system, regulatory aspects of MeHg transport across the bovine blood-brain barrier were investigated in isolated brain microvessel preparations. Following 1 hour co-incubations of 203 Hg-MeHgCl with 0.1 mM L-cysteine at 37 deg. C, 203 Hg uptake by suspended microvessels was significantly increased (P 203 Hg was abolished by co-incubations of microvessels with 0.1 mM L-cysteine-L-methionine, or 0.1 mM L-cysteine plus AT-125 (alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazolacetic acid), an irreversible inhibitor of gamma-glutamyl-transpeptidase. One hr co-incubations of bovine capilaries with 203 Hg-MeHgCl and 0.1 mM D-cysteine at 37 deg. C or 0.1 mM L-cysteine at 0 deg. did not increase rat of 203 Hg uptake compared with controls. These results indicate that L-cysteine enhances the rate of capillary MeHg uptake. The accumulation of 203 Hg in the bovine microvessels appears to be a carrier-mediated process. It is inhibited by L-methionin, a competitive substrate for neutral amino acid transport, and by AT-125. Capillary uptake of 203 Hg is stereospecific to the L-enantiomorph of cystine, suggesting selective uptake of MeHg across the blood-brain barrier. The data emphasize the relationship between the L-enantiomorph neutral amino acid carrier system and MeHg transport across the capillaries. (author)

  13. Immunochemical characterization of the brain glutamate binding protein

    International Nuclear Information System (INIS)

    Roy, S.

    1986-01-01

    A glutamate binding protein (GBP) was purified from bovine and rat brain to near homogeneity. Polyclonal antibodies were raised against this protein. An enzyme-linked-immunosorbent-assay was used to quantify and determine the specificity of the antibody response. The antibodies were shown to strongly react with bovine brain GBP and the analogous protein from rat brain. The antibodies did not show any crossreactivity with the glutamate metabolizing enzymes, glutamate dehydrogenase, glutamine synthetase and glutamyl transpeptidase, however it crossreacted moderately with glutamate decarboxylase. The antibodies were also used to define the possible physiologic activity of GBP in synaptic membranes. The antibodies were shown: (i) to inhibit the excitatory amino-acid stimulation of thiocyanate (SCN)flux, (ii) had no effect on transport of L-Glutamic acid across the synaptic membrane, and (iii) had no effect on the depolarization-induced release of L-glutamate. When the anti-GBP antibodies were used to localize and quantify the GBP distribution in various subcellular fractions and in brain tissue samples, it was found that the hippocampus had the highest immunoreactivity followed by the cerebral cortex, cerebellar cortex and caudate-putamen. The distribution of immunoreactivity in the subcellular fraction were as follows: synaptic membranes > crude mitochondrial fraction > homogenate > myelin. In conclusion these studies suggest that: (a) the rat brain GBP and the bovine brain GBP are immunologically homologous protein, (b) there are no structural similarities between the GBP and the glutamate metabolizing enzymes with the exception of glutamate decarboxylase and (c) the subcellular and regional distribution of the GBP immunoreactivity followed a similar pattern as observed for L-[ 3 H]-binding

  14. [Helicobacter pylori -- 2010].

    Science.gov (United States)

    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.

  15. Non-invasive Investigations for the Diagnosis of Fontan-Associated Liver Disease in Pediatric and Adult Fontan Patients

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    Amyna Fidai

    2017-03-01

    Full Text Available Fontan-associated liver disease (FALD is a serious complication related to the chronically elevated venous pressure and low cardiac output of this abnormal circulation. However, diagnostic markers for this condition are limited. We hypothesized that specific tests for fibrosis developed for other chronic liver diseases would identify a higher prevalence of FALD than ultrasound and standard laboratory tests and that identified abnormalities would correlate with time post-Fontan. In this cross-sectional study, we assessed 19 children (average age 8.4 ± 4.3 and 5.4 ± 4.1 years post-Fontan and 8 adults (average age 31.5 ± 8.9 and 21.1 ± 4 years post-Fontan using standard serum laboratory investigations assessing hepatic integrity and function, the FibroTest, liver ultrasound, and transient elastography (FibroScan. In adult Fontan patients, hemoglobin, C-reactive protein, and gamma-glutamyl transpeptidase were significantly increased, and white blood cell and platelet counts were significantly decreased in comparison to the pediatric cohort. International normalized ratio was mildly elevated in both children and adults. FibroTest results were suggestive of fibrosis regardless of time post-Fontan. FibroScan measurements were significantly correlated with time post-Fontan, but the incidence of ultrasound-detected liver abnormalities was variable. No cases of hepatocellular carcinoma were identified. Abnormalities suggestive of FALD occur in both children and adults post-Fontan. Select laboratory tests, and possibly ultrasound and FibroScan in some patients, appear to have the most promise for the non-invasive detection of FALD.

  16. Adrenergic regulation during acute hepatic infection with Entamoeba histolytica in the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB

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    Aldaba-Muruato Liseth Rubi

    2017-01-01

    Full Text Available Oxidative stress and transcriptional pathways of nuclear factor erythroid 2-related factor 2 (Nrf2 and nuclear factor kappa-B (NF-κB are critically involved in the etiopathology of amebic liver abscess (ALA. In this work, we studied the relationship between the adrenergic nervous system and ALA in the hamster. ALA was visible at 12 h of infection. While 6-hydroxidopamine (6-OHDA decreased infection, propranolol (β-adrenergic blocker treatment was associated with less extensive liver damage, and phentolamine treatment (α-adrenergic blocker significantly reduced ALA compared to 6-OHDA and propranolol. Serum enzymatic activities of alanine aminotransferase (ALT and γ-glutamyl transpeptidase (γ-GTP were increased at 12 h post-infection. Chemical denervation and α and β-adrenergic blockers decreased ALT to normal levels, while 6-OHDA and propranolol showed a trend to decrease γ-GTP but phentolamine significantly reduced γ-GTP. Amebic infection increased oxidized glutathione (GSSG and decreased both reduced glutathione (GSH and the GSH/GSSG ratio. Propranolol and 6-OHDA showed a tendency to decrease GSSG. However, GSH, GSSG and GSH/GSSG returned to normal levels with phentolamine. Furthermore, amebic infection increased pNF-κB and interleukin-1β (IL-1β, and showed a tendency to decrease hemoxigenase-1 (HO-1, but not Nrf2. Chemical denervation showed a trend to decrease pNF-κB and IL-1β, and neither Nrf2 nor HO-1 increased significantly. In addition, NF-κB and IL-1β were attenuated by propranolol and phentolamine treatments, although phentolamine showed significant overexpression of Nrf2 and HO-1. This suggests that the adrenergic system may be involved in oxidative stress and in modulation of the Nrf2 and NF-κB pathways during ALA development.

  17. Association between serum concentrations of persistent organic pollutants and smoking in Koreans: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ho Jung Moon

    2017-02-01

    Full Text Available Background: Studies on the associations between persistent organic pollutants (POPs and smoking according to gender and smoking amount (cigarettes/day are limited, and the results regarding the relationship between POPs and smoking are not completely consistent across studies. Objectives: The smoking rate in Korea is one of the highest among the Organization for Economic Cooperation and Development (OECD countries. We investigated the association between serum concentrations of POPs and cigarette smoking in Koreans by smoking status (never-smoker/ever-smoker and smoking amount (cigarettes/day according to gender. Methods: Serum concentrations of 32 polychlorinated biphenyls (PCBs and 19 organochlorine pesticides (OCPs were measured in 401 participants (232 men and 169 women who received health examinations during the Korean Cancer Prevention Study-II. We compared POP levels in ever-smokers and never-smokers and conducted multivariate logistic regression analyses to identify associations between POPs and smoking. Results: Among women, the concentrations of PCB 156, PCB 167, and PCB 180 were significantly higher in ever-smokers than in never-smokers. After adjustments for age, body mass index, gamma-glutamyl transpeptidase, and alcohol intake, serum PCB 157 concentration was positively associated with male ever-smokers (OR 2.26; 95% CI, 1.01–5.04. In addition, trans-nonachlordane in OCPs as well as PCBs was significantly positively related with female ever-smokers (OR 3.21; 95% CI, 1.04–9.86. We found that subjects who smoked fewer than 15 cigarettes/day had a higher risk of having high POP concentrations than never-smokers. Conclusions: These results indicate that smoking may be associated with human serum POPs levels.

  18. Alcoholic Ketosis: Prevalence, Determinants, and Ketohepatitis in Japanese Alcoholic Men.

    Science.gov (United States)

    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 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.

  19. Serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide

    Directory of Open Access Journals (Sweden)

    Jinjiang He

    2015-04-01

    Full Text Available Objectives: The aim of this study has been to investigate serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide (DMF. Material and Methods: Seventy-two workers and 72 healthy controls participated in the study. All subjects underwent complete physical examinations and abdominal ultrasound examination. Serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and c-glutamyl transpeptidase (c-GT were determined by an auto-chemistry analyzer. The data of airborne concentrations of DMF was obtained from the local Center of Disease Control and Prevention. The level of urine N-acetyl-S-(N-methylcarbamoylcysteine (AMCC was measured by means of high-performance liquid chromatography. Results: Time weighted average (TWA concentration of the DMF in workplace was 18.6 (range: 9.8–36.2 mg/m3. The concentration of the AMCC in workers’ urine was 28.32 (range: 1.8–58.6 mg/l and 9 workers’ AMCC exceeded the biological exposure index (40 mg/l. Thirty-one workers reported gastrointestinal symptoms (abdominal pain, nausea, anorexia and 10 workers reported headache, dizziness and/or palpitation in the exposed group. Serum analysis revealed that both the mean of serum activities of liver enzymes (ALT, AST and c-GT and the percentage of workers with abnormal liver function were significantly higher in the exposed group as compared to the controls. Conclusions: Dimethylformamide can cause liver damage even if air concentration is in the sub-threshold limit value (sub-TLV level. The protection of skin contact against the exposure to the DMF might be a critical issue as far as the occupational health is concerned.

  20. Request of laboratory liver tests in primary care in Spain: potential savings if appropriateness indicator targets were achieved.

    Science.gov (United States)

    Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Uris, Joaquín; Leiva-Salinas, Carlos

    2015-10-01

    Liver laboratory tests are used to screen for liver disease, suggest the underlying cause, estimate the severity, assess prognosis, and monitor the efficacy of therapy. The aim of this study was to compare the liver laboratory tests requesting patterns by GPs in Spain, according to geographic and hospital characteristics, to investigate the degree of requesting appropriateness. One hundred and forty-one clinical laboratories were invited to participate from diverse regions across Spain. They filed out the number of laboratory liver tests requested by GPs for the year 2012. Two types of appropriateness indicators were calculated: every test request per 1000 inhabitants or ratios of related tests requests. The indicator results obtained were compared between the different hospitals, according to their setting, location, and management. The savings generated, if each area would have achieved indicator targets, were calculated. We recruited 76 laboratories covering a population of 17,679,195 inhabitants. GPs requested 20,916,780 laboratory liver tests in the year 2012. No differences were obtained according to their setting. Lactate dehydrogenase and direct bilirubin per 1000 inhabitants were significantly higher in institutions with private management. Largest differences were observed between communities. Nine, 31, 0, and 13 laboratories, respectively, achieved the aspartate aminotransferase, lactate dehydrogenase, γ-glutamyl transpeptidase, and total bilirubin-related alanine aminotransferase indicator targets. Reaching ratios would have resulted in savings of €1,028,468. There was a high variability in the request of liver tests. This emphasizes the need to implement interventions to improve appropriate use of liver tests.

  1. Unwanted road to anaemia in transthyretin familial amyloid polyneuropathy may continue irrespective of tafamidis treatment.

    Science.gov (United States)

    Ikeda, Tokunori; Masuda, Teruaki; Ueda, Mitsuharu; Yamashita, Taro; Misumi, Yohei; Shinriki, Satoru; Ando, Yukio

    2018-01-01

    Background This retrospective longitudinal study was performed to determine whether tafamidis treatment leads to improvements in commonly used blood data for transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods Commonly used blood data (complete blood count [including a haemogram], total protein, albumin, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase, total bilirubin [T-Bil], creatine kinase, choline esterase, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, estimated glomerular filtration rate [eGFR], serum amyloid A protein, TTR, haemoglobin A1c, free triiodothyronine [FT3] and free thyroxine [FT4]) were investigated in 33 TTR-FAP patients. These values included longitudinal data at three time points: six months before or after tafamidis treatment and one year after tafamidis treatment. Longitudinal changes in each blood item were examined using a linear mixed model, adjusting for age at starting tafamidis, sex, TTR-FAP stage and value before tafamidis treatment. Results Our results show elevated TTR concentrations after tafamidis treatment. In contrast, haemoglobin, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, mean platelet volume, platelet distribution width, T-Bil, eGFR, FT3 and FT4, gradually decreased through a reference range. There were no characteristic observations in any other items. TTR binds to thyroid hormone; therefore, FT3 and FT4 decreased in inverse proportion to increased TTR concentrations. Conclusion Unfortunately, progression to anaemia may occur regardless of tafamidis treatment. Because anaemia is sometimes present in TTR-FAP, attention should be paid to longitudinal changes in commonly used blood data, irrespective of tafamidis treatment.

  2. Serotonergic neurotoxic metabolites of ecstasy identified in rat brain.

    Science.gov (United States)

    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

  3. Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury.

    Science.gov (United States)

    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.

  4. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    International Nuclear Information System (INIS)

    Chen, Y.-J.; Liao, H.-F.; Tsai, T.-H.; Wang, S.-Y.; Shiao, M.-S.

    2005-01-01

    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-κB 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 of 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 γ-glutamyl transpeptidase activity. Radiation activated NF-κB 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-κB activity, without toxicity to bone marrow, liver, and kidney

  5. Dietary Supplementation with Lactobacillus casei Alleviates Lipopolysaccharide-Induced Liver Injury in a Porcine Model

    Directory of Open Access Journals (Sweden)

    Di Zhao

    2017-11-01

    Full Text Available This study aims to determine whether Lactobacillus casei (L. casei could relieve liver injury in piglets challenged with lipopolysaccharide (LPS. Piglets were randomly allocated into one of the three groups: control, LPS, and L. casei. The control and LPS groups were fed a corn- and soybean meal-based diet, whereas the L. casei group was fed the basal diet supplemented with 6 × 106 cfu/g L. casei. On Day 31 of the trial, piglets in the LPS and L. casei groups received intraperitoneal administration of LPS (100 µg/kg body weight, while the control group received the same volume of saline. Blood and liver samples were collected for analysis. Results showed that L. casei supplementation decreased the feed/gain ratio (p = 0.027 and diarrhea incidence (p < 0.001, and attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, LPS challenge dramatically increased glutamyl transpeptidase activity (p = 0.001 in plasma as well as the concentrations of Interleukin 6 (IL-6 (p = 0.048, Tumor necrosis factor-alpha (TNF-α (p = 0.041, and Malondialdehyde (MDA (p = 0.001 in the liver, while decreasing the hepatic SOD activity. LPS also increased (p < 0.05 the mRNA levels for IL-6, IL-8, TNF-α, Toll-like receptors 4 (TLR4, Nuclear factor κB (NF-κB and Heat shock protein 70 (HSP70 in the liver. The adverse effects of LPS challenge were ameliorated by L. casei supplementation. In conclusion, dietary L. casei alleviates LPS-induced liver injury via reducing pro-inflammatory cytokines and increasing anti-oxidative capacity.

  6. Protective effects of Urtica dioica seed extract in aflatoxicosis: histopathological and biochemical findings.

    Science.gov (United States)

    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.

  7. Genotoxic and carcinogenic risks associated with the dietary consumption of repeatedly heated coconut oil.

    Science.gov (United States)

    Srivastava, Smita; Singh, Madhulika; George, Jasmine; Bhui, Kulpreet; Murari Saxena, Anand; Shukla, Yogeshwer

    2010-11-01

    Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeated heating of edible oils can generate a number of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported to have carcinogenic potential. Consumption of these repeatedly heated oils can pose a serious health hazard. The objectives of the present study were to evaluate the genotoxic and carcinogenic risks associated with the consumption of repeatedly heated coconut oil (RCO), which is one of the commonly consumed cooking and frying medium. The PAH were analysed using HPLC in fresh CO, single-heated CO (SCO) and RCO. Results revealed the presence of certain PAH, known to possess carcinogenic potential, in RCO when compared with SCO. Oral intake of RCO in Wistar rats resulted in a significant induction of aberrant cells (P<0·05) and micronuclei (P<0·05) in a dose-dependent manner. Oxidative stress analysis showed a significant (P<0·05) decrease in the levels of antioxidant enzymes such as superoxide dismutase and catalase with a concurrent increase in reactive oxygen species and lipid peroxidation in the liver. In addition, RCO given alone and along with diethylnitrosamine for 12 weeks induced altered hepatic foci as noticed by alteration in positive (γ-glutamyl transpeptidase and glutathione-S-transferase) and negative (adenosine triphosphatase, alkaline phosphatase and glucose-6-phosphatase) hepatospecific biomarkers. A significant decrease in the relative and absolute hepatic weight of RCO-supplemented rats was recorded (P<0·05). In conclusion, dietary consumption of RCO can cause a genotoxic and preneoplastic change in the liver.

  8. Daconate Herbicide Toxicity on Lipid Peroxidation And Antioxidant Enzymes in Blood of Rats

    International Nuclear Information System (INIS)

    Tawfik, S.M.F.

    2005-01-01

    The effect of daconate herbicide on lipid peroxidation and antioxidant enzyme systems was investigated in rats after one and two weeks post-treatment. Animals were treated daily with an oral dose of 18 mg/kg body weight or 90 mg/kg body weight daconate for one and two consecutive weeks. Lipid peroxide content, as thiobarbituric acid reactive substances (TBARS), was determined in blood of rats as indication for cytotoxicity. Blood glutathion (GSH), gamma glutamyl transpeptidase (γ GT) and superoxide dismutase (SOD) were estimated as indication of antioxidant status. Also, daconate effect on peroxidase action of catalase in rats was studied using 14 C -formate. The results revealed significant elevation in TBARS level and γ GT activity accompanied by reduced level of GSH content and SOD activity after treatment of rats with a daily oral dose of 90 mg/kg for one and two weeks and also in rats treated with 18 mg/kg daconate for two weeks. Rats treated with daconate at the dose level of 18 mg/kg for one week revealed non-appreciable changes in the tested parameters of blood as compared to the control ones. Radioactivities eliminated in both the expired air and in urine were reduced at the dose level of 90 mg/kg after one and two weeks, while it were reduced only after two weeks at the dose level of 18 mg/kg daconate. The data revealed that daconate had a marked effect on the activities of catalase enzyme in blood and liver of treated rats

  9. Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions.

    Science.gov (United States)

    Nanau, Radu M; Neuman, Manuela G

    2015-06-29

    The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010-2015). The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

  10. Oral administration of Saccharomyces boulardii alters duodenal morphology, enzymatic activity and cytokine production response in broiler chickens.

    Science.gov (United States)

    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.

  11. Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

    Science.gov (United States)

    Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

    2011-01-01

    Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

  12. Concurrent low brain and high liver uptake on FDG PET are associated with cardiovascular risk factors

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    Nam, Hyun Yeol [Dept. of Nuclear Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon (Korea, Republic of); Jun, Sung Min [Dept. of Nuclear Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan (Korea, Republic of); Pak, Kyoung June; Kim, In Joo [Dept. of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of)

    2017-04-15

    Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without.

  13. Effects of different starch sources on metabolic profile, production and fertility parameters in dairy cows.

    Science.gov (United States)

    Mikuła, R; Nowak, W; Jaśkowski, J M; Maćkowiak, P; Oszmałek, E Pruszyńska

    2011-01-01

    The objective of the study was to determine the effect of replacing triticale (high rumen degradable starch) with maize grain (low rumen degradable starch) during the transition period and the first 120 days of lactation on metabolic and hormonal profile indices, milk production and fertility performance in cows. Forty-eight Holstein-Friesian dairy cows were divided into 4 groups: TT (2.5 kg triticale grain/cow per day supplemented from 14 days prepartum to day 120 postpartum), TM (2.5 kg triticale grain/cow per day supplemented from day 14 before parturition to calving, and then 2.5 kg maize grain to 120 days of lactation), MT (2.5 kg maize grain/cow per day supplemented from day 14 before parturition to calving, and then 2.5 kg triticale grain to 120 days of lactation), MM (2.5 kg maize grain/cow per day supplemented from 14 days prepartum to day 120 postpartum). Blood samples were collected 3 weeks and 1 week before calving and on days 14, 56 and 70 of lactation, and they were analyzed in terms of concentrations of glucose, insulin, leptin, insulin-like growth factor I, nonesterified fatty acids, triglycerides, cholesterol, blood urea nitrogen and activities of aspartate aminotransferase and gamma glutamyl transpeptidase. Milk samples were collected twice a day at weekly intervals and analyzed for fat, protein and lactose. Milk yield and individual dry mater intake were recorded at weekly intervals. Body condition was estimated 3 weeks before calving, on parturition day and on days 14, 56 and 120 of lactation. Replacing triticale grain with maize grain in the transition period and during lactation positively affected fertility of lactating cows. An increased first service conception rate and shortening of the days open period was observed in MM and TM groups in comparison to those found in group MT (P cows than triticale grain.

  14. LDL-cholesterol lowering effect of a new dietary supplement: an open label, controlled, randomized, cross-over clinical trial in patients with mild-to-moderate hypercholesterolemia.

    Science.gov (United States)

    Magno, S; Ceccarini, G; Pelosini, C; Jaccheri, R; Vitti, J; Fierabracci, P; Salvetti, G; Airoldi, G; Minale, M; Saponati, G; Santini, F

    2018-05-24

    Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. LDL-C decreased by 23.3% during treatment with N (p ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL. ClinicalTrials.gov ID: NCT03425630 .

  15. Synthesis and Sensory Characteristics of Kokumi γ-[Glu]n-Phe in the Presence of Glutamine and Phenylalanine: Glutaminase from Bacillus amyloliquefaciens or Aspergillus oryzae as the Catalyst.

    Science.gov (United States)

    Yang, Juan; Sun-Waterhouse, Dongxiao; Cui, Chun; Dong, Keming; Wang, Wei

    2017-10-04

    The transpeptidase activity of glutaminase from Bacillus amyloliquefaciens (GBA) and Aspergillus oryzae (GAO) to yield γ-[Glu] n -Phe peptides were verified for the first time. In the presence of Gln and Phe, γ-Glu-Phe and γ-Glu-γ-Glu-Phe were synthesized by GAO, and γ-Glu-Phe, γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe, and γ-Glu-γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe were synthesized by GBA. The K m values for the transpeptidation catalyzed by GBA and GAO were 47.88 and 153.92 mM (Phe as the acceptor), 84.89 and 236.47 mM (γ-Glu-Phe as the acceptor), indicating that GBA had a greater affinity than GAO for Phe and γ-Glu-Phe in the transpeptidation reaction. The K m values for the transpeptidation catalyzed by GBA against acceptors, Phe and γ-[Glu] (1≤n<5) -Phe (47.88-206.47 mM), increased with an elevated number of γ-glutamyl residue within the acceptor. The optimal conditions for γ-[Glu] n -Phe synthesis were pH 10 and 37 °C for 3 h, 300 mM Gln, 100 mM Phe, 0.05 U/mL GBA. All the γ-[Glu] (1≤n≤5) -Phe exhibited astringency in water and imparted a kokumi taste to commercial soy sauce and model chicken broth. The astringent threshold values (2.5-3.92 mM) were approximately 3-fold of the kokumi threshold concentrations (0.78-1.53 mM). γ-[Glu] n -Phe or the post-enzymatic reaction mixture enhanced the umami intensity of commercial soy sauce and model chicken broth.

  16. Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models

    International Nuclear Information System (INIS)

    Xing, Jiali; Wang, Gang; Zhao, Jichun; Wang, Eryin; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q.; Chen, Wei

    2016-01-01

    Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD_5_0 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS. - Highlights: • The acute and subchronic toxicity of PFOS was systematically investigated. • The acute oral LD_5_0 value for PFOS in C57BL/6J mice was 0.579 g/kg body weight. • PFOS disrupted the homeostasis of antioxidative systems. • PFOS induced hepatocellular apoptosis and triggered liver injury. - PFOS disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis, and triggered liver injury.

  17. Trajectories of Alcohol Use Disorders and Their Differential Impact: A Population-Based Cohort Study in Goa, India.

    Science.gov (United States)

    Nadkarni, Abhijit; Weiss, Helen A; Bhat, Bhargav; Patel, Vikram

    2017-09-01

    The aim of this study was to examine trajectories of Alcohol Use Disorders (AUD) over a 6 year period and compare the bio-psycho-social correlates between these trajectories. Community-based cohort of 1899 adult men were interviewed in 2006-2008 and 2012-2014. AUD were assessed using the Alcohol Use Disorder Identification Test, and potential correlates including psycho-social problems, morbidity and physiological parameters were measured at follow-up. Logistic regression was conducted to estimate odds ratios (ORs) for the association of persistent and incident AUD, respectively, with the potential correlates. Analyses were weighted to account for sampling design, number of adults aged 18-49 years in the household and non-response. Compared with men who had recovered from AUD, there was strong evidence (P < 0.001) that men with persistent AUD were more likely to have marital problems, tobacco use, and raised Gamma Glutamyl Transferase (GGT) and strong evidence (0.001 < P < 0.01) that they were more likely to have workplace problems, social problems, increased healthcare contact and raised Mean Corpuscular Volume (MCV). Compared with men who did not have AUD at baseline and follow-up, there was strong evidence (P < 0.001) that men with incident AUD were more likely to have workplace problems, social problems, marital problems, tobacco use, and raised GGT and strong evidence (0.001 < P < 0.01) that they were more likely to have hypertension, accident and injuries and Common Mental Disorders (CMD). This community-based longitudinal study of AUD, the first from a low and middle income country, clearly demonstrates significant health and social consequences of AUD in men and highlights the need for interventions for their treatment and prevention. Compared to persistent AUD, recovery from AUD has several benefits in health and social domains. Compared to developing new AUD, not having AUD has several benefits in health and social domains. Sustaining the state of not

  18. The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

    Science.gov (United States)

    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

  19. Elevated Apoptosis in the Liver of Dairy Cows with Ketosis.

    Science.gov (United States)

    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

  20. Elevated Apoptosis in the Liver of Dairy Cows with Ketosis

    Directory of Open Access Journals (Sweden)

    Xiliang Du

    2017-09-01

    Full Text Available Background/Aims: 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. Methods: 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. Results: 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

  1. Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

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    Michiel Sala

    Full Text Available OBJECTIVE: Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT. RESEARCH DESIGN AND METHODS: We measured nonfasting alanine transaminase (ALT, aspartate aminotransferase (AST, and Υ-glutamyl transferase (GGT in 1625 subjects (736 men, mean age 59.1 years from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230 were evaluated and CT was performed (n = 268 for assessment of liver-spleen (L/S ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD. Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. RESULTS: Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03, while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively. CONCLUSIONS: Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver

  2. Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

    Science.gov (United States)

    Sala, Michiel; Kroft, Lucia J M; Röell, Boudewijn; van der Grond, Jeroen; Slagboom, P Eline; Mooijaart, Simon P; de Roos, Albert; van Heemst, Diana

    2014-01-01

    Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively). Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and

  3. 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

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    Shekoohi-Shooli F.

    2016-09-01

    Full Text Available 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 (HDLand 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

  4. Efficacy of albendazole in combination with thymol against Echinococcus multilocularis protoscoleces and metacestodes.

    Science.gov (United States)

    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

  5. Haematological and serum biochemical reference values in free-ranging red deer (Cervus elaphus atlanticus

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    Olav Rosef

    2004-04-01

    Full Text Available Analyses of haematological and biochemical constituents were carried out on the Norwegian subspecies of free-ranging red deer (Cervus elaphus atlanticus. All animals were captured from January to March by using a mixture of xylazine and tiletamin-zolazepam. Immobilisation was performed with plastic projectile syringes fired from a dart gun. Fourteen haematological parameters were analysed. There were no differences in the values between hinds and stags and between adults and calves (P > 0.01. Of the 22 biochemical compounds investigated there was a significant difference (P < 0.01 between calves and adults for lactate dehydrogenase (LD, globulin, beta globulin, gamma globulin, and the minerals Na, K, Mg, Zn, Ca, and P. Differences (P < 0.01 between hinds and stags were found in cholesterol, gamma glutamyl transferase (GGT, alpha-1 globulin, alpha-2 globulin and Cu. The blood values determined in this study can be used as reference values for this red deer subspecies immobilised with a mixture of xylazine-tiletamin-zolazepam for health control and diagnosis of diseases.Abstract in Norwegian /Sammendrag:Hematologiske og biokjemiske parametere er analysert på norsk frittlevende hjort (Cervus elaphus atlanticus. Hjorten ble immobilisert i tidsrommet januar til mars ved hjelp av et spesialgevær ladet med plast kanyler som inneholdt en blanding av xylazin og tiletamin-zolazepam. Det var ingen forskjeller i de14 undersøkte hematologiske verdiene mellom hinder, kalver og bukker (P>0,01. Av de 22 biokjemiske parametrene som ble undersøkt var det en signifikant forskjell mellom kalver og voksne (P<0,01 når det gjelder laktat dehydrogenase, globulin, beta globulin, gamma globulin og mineralene Na, K, Mg, Zn, Ca og P. Det var en signifikant forskjell mellom hinder og bukker (P<0.01 på parametrene kolesterol, gamma glutamyl transferase, alfa-1 globulin, alfa-2 globulin og Cu. Blodverdiene som ble målt i dette studiet kan bli brukt som referanseverdier

  6. Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in preoperative chemoradiotherapy for patients with rectal cancer.

    Science.gov (United States)

    Sadahiro, Sotaro; Suzuki, T; Tanaka, A; Okada, K; Saito, G; Miyakita, H; Ogimi, T; Nagase, H

    2017-06-01

    Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay. A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

  7. Effects of Portulaca oleracea L. seeds in treatment of type-2 diabetes mellitus patients as adjunctive and alternative therapy.

    Science.gov (United States)

    El-Sayed, Mohamed-I Kotb

    2011-09-01

    ETHNPHARMACOLOGICAL RELEVANCE: To investigate antidiabetic activity of purslane seeds on type-2 diabetic subjects and to provide scientific basis for the clinical use of Portulaca oleracea (PO). A thirty subject with type-2 diabetes divided into two groups, to receive 5 g of PO seeds twice daily while in the second group, their participants receive 1,500 mg of metformin/day. All participants were requested to report the effects of treatments on diabetic manifestations, their weights, body mass index (BMI), adverse effects, fasting and post-prandial blood glucose during treatment schedule. Blood samples from participants before and after treatment were taken for serum separation, which are used for measurement of serum lipids, liver enzymes, total and direct bilirubin, albumin, and insulin. It showed a significant decrease in serum levels of triglycerides (TGs), total cholesterol (T(C)), low density lipoprotein cholesterol (LDL(C)), liver alanine-, aspartate- and gamma glutamyl transaminase (ALT, AST, and GGT), total and direct bilirubin, fasting and post-prandial blood glucose, insulin, body weight and BMI while a significant increase in high density lipoprotein cholesterol (HDL(C)) and albumin but non-significant change of alkaline phosphatase (ALP) in PO seeds treated subjects. Metformin (M) group has the same results of PO group except in high density lipoprotein cholesterol (HDL(C)), LDL(C), and ALP levels had a different pattern. PO seeds could be effective and safe as adjuvant therapy for Type-2 diabetic subjects. These results demonstrated that PO seeds possessed notable hypoglycaemic, hypolipidaemic and insulin resistance reducer effects; possibly due to its contents of polyunsaturated fatty acids, flavonoids, and polysaccharides. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    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 (pbiochemistry. 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 associated with ALP but not with other liver biochemistry parameters.

  9. The Efficacy of Coffee and Green Tea in Ameliorating Histological and Biochemical Changes Induced By γ-Irradiation in Albino Rats

    International Nuclear Information System (INIS)

    Rezk, R.G.; Darwish, M.M.

    2009-01-01

    Exposure to ionizing radiation results in oxidative damage, organ dysfunction and metabolic disturbances. The aim of the present study was to investigate the efficacy of coffee, green tea, or coffee + green tea consumption on radiation-induced damage in liver and heart tissues of rats. Rats received/day, by gavages, the water extract of 0.3 g green tea and/or 0.2 g coffee, for a period of 7 days. The last dose was given 60 min before irradiation with a dose of 6.5 Gy. Histological examination through light microscope of sections in the liver and heart tissues on the 3rd day post-irradiation revealed that all treatments has attenuated radiation-induced oxidative damage. Necrosis, apoptosis, cell death and rupture of cell membrane in both tissues were less severe and were associated with significant decrease of serum malonaldehyde (MDA) content and significant increase in superoxide dismutase (SOD) and catalase (Cat) activities, and glutathione (GSH) content, compared to their corresponding value in non irradiated rats. The results were substantiated by significant amelioration in the activity of serum lactate dehydrogenase (LDH), aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) and the content of triglycerides (TG) and total cholesterol (TC), markers of liver and heart functions. No significant changes were recorded between the 3 treatments. However, coffee + green tea provoked better results with respect to radiation-induced lipid peroxidation, which might be attributed to their synergistic effect as free radical scavengers. It could be concluded that drinking coffee associated with green tea is healthier than drinking coffee or green tea alone to protect liver and heart tissues from oxidative stress

  10. The correlates of urinary albumin to creatinine ratio (ACR) in a high risk Australian aboriginal community.

    Science.gov (United States)

    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.

  11. Liver and Kidney Functional Indices of Pregnant Rats Following the Administration of the Crude Alkaloids from Senna alata (Linn. Roxb Leaves

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    Musa Toyin Yakubu

    2012-05-01

    Full Text Available Background: Alkaloids from Senna alata leaves implicated as the active constituents of abortifacient are yet to be investigated for their effects on the normal functioning of the maternal liver and kidney. Therefore, the effects of crude alkaloids on some biochemical indices of kidney and liver damage were investigated in pregnant rats. Methods: Pregnant rats were randomized into 4 groups: A (control, B, C, and D and were orally administered 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the alkaloids respectively once daily on days 10-18 post coitum. Results: Thin-layer chromatographic separation gave five spots with Rf values of 0.28, 0.33, 0.39, 0.47, and 0.55 that produced creamy precipitate and reddish-brown colour, respectively, with Mayer’s and Wagner’s reagents. Quantitative determination gave 0.30 g which corresponded to a percentage yield of 1.50 % of the alkaloids. The decreases in the activities of alkaline phosphatase (ALP, gamma glutamyl transferase (GGT, aspartate (AST and alanine transaminases in the liver and kidney of the animals by the alkaloids were accompanied by corresponding increases in the serum enzymes. The alkaloids reduced liver- and kidney-body weight ratios, serum globulin, urea, uric acid, and phosphate ions while the serum concentrations of albumin, bilirubin, creatinine, potassium ions, AST/ALT ratio, blood urea nitrogen: creatinine increased. The levels of sodium, calcium, and chloride ions did not change significantly (P>0.05. Conclusion: Overall, the alkaloid at doses of 250-1000 mg/kg body weight produced permeability changes in the plasma membrane of the organs and adversely affected the normal secretory, synthetic, and excretory functions of these organs.

  12. Analysis of the hematological and biochemical parameters related to lead intoxication.

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    Yılmaz, Hınç; Keten, Alper; Karacaoğlu, Emre; Tutkun, Engin; Akçan, Ramazan

    2012-11-01

    In parallel with industrial advancements, number of the occupational diseases secondary to chemical exposure is increasing. The chemical agents in the work places affect various organ and tissue systems, leading to chronic diseases. In this study, the cases diagnosed with occupational disease due to exposure to lead were studied and importance of the environmental forensic sciences on this issue was emphasized. A hundred and ninety patients diagnosed with occupational disease related to lead intoxication in Ankara Occupational Diseases Hospital between 01/01/2009 and 31/12/2009 were included in the study. Twenty cases were used as the controls. Sociodemographic characteristics, serum chemical parameters and hematological parameters of the patients were retrospectively assessed. Mean age of the cases included in the study was 35.3±8.69. Hemoglobin (Hb) (p=0.018) and Mean corpuscular volume (MCV) (plead exposure than in the controls. Gamma glutamyl transferase (GGT) was significantly lower in the patients with lead exposure than in the controls (p=0.002), whereas alkaline phosphatase (ALP) was found higher (plead exposure than in the control group (p=0.01), while Thyrotrophin-stimulating hormone (TSH) levels were lower (plead (Pb) was correlated positively with ALP values and negatively with Hb, MCV and TSH. Considering its effects on the biochemical and hematological parameters, a detailed investigation should be carried out in the cases with lead exposure, which occupies an important place among the occupational diseases. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  13. Association between Healthy Eating Index-2010 and Fetuin-A Levels in Patients with Type 2 Diabetes: a Case-Control Study.

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    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.

  14. Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes?

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    Ashley M Miller

    Full Text Available Preliminary data mostly from animal models suggest the sST2/IL-33 pathway may have causal relevance for vascular disease and diabetes and thus point to a potential novel inflammatory link to cardiometabolic disease. However, the characterisation of sST2 levels in terms of metabolic or vascular risk in man is completely lacking. We sought to address this gap via a comprehensive analysis of risk factor and vascular correlates of sST2 in a cross-sectional study (pSoBid. We measured sST2 in plasma in 639 subjects and comprehensively related it to cardiovascular and diabetes risk factors and imaged atherosclerosis measures. Circulating sST2 levels increased with age, were lower in women and in highest earners. After adjusting for age and gender, sST2 levels associated strongly with markers of diabetes, including triglycerides [effect estimate (EE per 1 standard deviation increase in sST2:1.05 [95%CI 1.01,1.10], liver function (alanine aminotransaminase [ALT] and γ-glutamyl transferase [GGT]: EE 1.05 [1.01,1.09] and 1.13 [1.07,1.19] respectively, glucose (1.02 [1.00,1.03] and sICAM-1 (1.05 [1.02,1.07]. However, sST2 levels were not related to smoking, cholesterol, blood pressure, or atheroma (carotid intima media thickness, plaque presence. These results suggest that sST2 levels, in individuals largely without vascular disease, are related principally to markers associated with diabetes and ectopic fat and add support for a role of sST2 in diabetes. Further mechanistic studies determining how sST2 is linked to diabetes pathways may offer new insights into the inflammatory paradigm for type 2 diabetes.

  15. Analysis of medical and psychological certificates concerning drivers who drove after alcohol use

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    Ewa Latała-Łoś

    2014-08-01

    Full Text Available Background: The aim of the study is to present the health predispositions to drive, assessed during certifying people referred to the Regional Centre for Occupational Medicine in Kielce due to drunk driving or driving after using alcohol. The article mainly presents the results regarding the prevalence of alcohol dependence and other psychiatric disorders in this group. We analyzed health condition at 3 year intervals in the years 2004, 2007 and 2010, adding the population of those who were examined in 2011. Material and Methods: A total of 5701 people were involved, both men and women. Drivers test cards along with the results of biochemical tests and specialist consultations were analyzed. The analysis of the results was performed using the statistical package PQStat 1.4.2.324 Results: Certificates with health contraindications to drive were issued to 6.7% of investigated individuals. Very significant correlation between alcohol dependence syndrome and the level of γ-glutamyl transferase (GGT, alanine aminotransferase (ALT, and aspartate aminotransferase (AST were confirmed. Alcohol dependence was diagnosed in 3.8% of the group. Conclusions: The health state of the drivers met the required certification criteria necessary for obtaining a driving license in more than 93% of the group. The study revealed many diseases in the group of investigated drivers, including 3.8% of alcohol dependence and 5% of mental disorders. The threat of losing driving license has become an important factor motivating drivers to undertake therapy. However, it seems advisable to develop principles for treatment monitoring and exchange of information between the certifying physician and the treating psychiatrist or psychologist. Med Pr 2014;65(4:497–506

  16. Potential impact of Paracentrotus lividus extract on diabetic rat models induced by high fat diet/streptozotocin

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    Amel M. Soliman

    2016-10-01

    Full Text Available Antioxidant therapy has been thought to be effectual for the prevention and treatment of various diseases including diabetes. Therefore, the present study was designed to investigate the potency of Paracentrotus lividus extract (PLE for alleviating the complications that resulted after induction of the diabetic rat models (T1DM and T2DM using high fat diet (HFD/streptozotocin (STZ. Thirty six male Wistar albino rats were assigned into normal control, T1DM and T2DM untreated, and PLE treated diabetic rat groups. Induction of T1DM was performed by streptozotocin injection (60 mg/kg of dissolved in sodium citrate buffer, 0.1 mol/L, i.p. T2DM induction through 4 weeks of high fat diet (HFD intervention was followed by a single low dosage of STZ (30 mg/kg dissolved in 0.1 mol/L citrate buffer at pH 4.5, i.p. Both diabetic rat models showed a significant increase in serum; levels of fasting glucose, total protein, bilirubin, activities of arginase, transaminases (AST and ALT, alkaline phosphatase (ALP, γ glutamyl transferase (GGT, lipid profile parameters, and liver malondialdehyde (MDA. However, T1DM and T2DM rats have decreased levels of serum insulin, and liver glucose 6 phosphate dehydrogenase (G6PD, glutathione reduced (GSH, nitric oxide (NO, and antioxidant enzymes. Furthermore, the present study showed the hypoglycemic, hypolipidemic, and antioxidant potency of the PLE as confirmed by its ability for ameliorating most of the alterations caused in the studied parameters of diabetic rats. In conclusion, PLE may be useful as therapy against oxidative stress and liver damage in both types of diabetes mellitus and is therefore recommended for further studies.

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

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    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.

  18. ASSOCIATION OF CARDIORESPIRATORY FITNESS WITH ELEVATED HEPATIC ENZYME AND LIVER FAT IN JAPANESE PATIENTS WITH IMPAIRED GLUCOSE TOLERANCE AND TYPE 2 DIABETES MELLITUS

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    Mayumi Nagano

    2010-09-01

    Full Text Available No study has so far determined whether a favorable level of cardiorespiratory fitness (CF contributes to a reduced risk of elevated hepatic enzymes and a high degree of liver fat in patients having various metabolic risks. This study investigated the association between the maximal oxygen uptake (VO2 max and the prevalence of elevated liver enzymes and high liver fat, while considering such factors as abdominal obesity, hyperinsulinemia and the other metabolic risks. The study enrolled newly diagnosed Japanese patients (n = 84; 52 males and 32 females; aged 25-69 years with impaired glucose tolerance (IGT and type 2 diabetes mellitus (Type2DM who did not receive any intervention or pharmacological therapy. The subjects were divided into 3 groups according to the distribution of the VO2max for each sex. The odds ratios (ORs for the prevalence of elevated aspartate and alanine aminotransferase (AST and ALT and high degree of liver fat adjusted for age, sex, disease type, daily ethanol intake, and current smoking were significantly lower in the moderate- and high CF groups in comparison to the low CF group. In addition, a significant OR for AST was maintained in the moderate and high CF group after adjusting for abdominal obesity and/or hyperinsulinemia. The significant ORs for the prevalence of elevated ALT and a high degree of liver fat were attenuated after adjusting for abdominal obesity and/or hyperinsulinemia. No significant OR for the prevalence of elevated gamma-glutamyl transferase (GGT was recognized in all logistic models. These results indicated that CF was negatively and independently associated with the prevalence of elevated AST even in Japanese diabetic patients having various metabolic risks. It was concluded that the AST level might be useful as a simple marker reflecting physical inactivity in such subjects

  19. Insulin resistance and the metabolic syndrome are related to the severity of steatosis in the pediatric population with obesity

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    Esther Ubiña-Aznar

    Full Text Available Background: To determine the factors associated with an increased risk for severe steatosis (SS and establish the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR as a screening tool. Methods: A cross-sectional study was performed in obese children to assess the relationship between the metabolic syndrome (MetS and glucose metabolism alterations (GMA and the risk for severe steatosis. Results: A total of 94 children (51 males aged from six to 14 years were included. Thirteen children (14.8% had severe steatosis (SS. The anthropometric variables associated with SS included body mass index (BMI (SS 34.1 vs non-SS 29.7, p = 0.005, waist circumference (cm (100 vs 92.5, p = 0.015 and hip circumference (cm (108 vs 100, p = 0.018. The blood parameters included alanine aminotransferase (ALT (UI/dl (27 vs 21, p = 0.002, gamma-glutamil transpeptidase (GGT (UI/dl (16 vs 15, p = 0.017, fasting glycemia (mg/dl (96 vs 88, p = 0.006, fasting insulin (UI/dl (25 vs 15.3, p < 0.001 and HOMA-IR score (7.1 vs 3.7, p < 0.001. Eighteen children with MetS were found to be at an increased risk for severe steatosis (odds ratio [OR] 11.36, p < 0.001. After receiver operating characteristic (ROC curve analysis, the best area under the curve (AUC was obtained for HOMA-R of 0.862. The HOMA-R 4.9 cut-off value had a 100% sensitivity (CI 95%: 96.2-100 and 67.9% specificity (CI 95%: 57.1-78.7 for severe steatosis. Conclusions: The presence of MetS and glucose metabolism alterations are risk factors for severe steatosis. The 4.9 cut-off value for HOMA-IR may be a risk factor for severe steatosis in obese children.

  20. Dapsone hypersensitivity syndrome in an adolescent during treatment during of leprosy Síndrome de hipersensibilidade à dapsona em uma adolescente durante tratamento de hanseníase

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    Fábio Bucaretchi

    2004-04-01

    Full Text Available A 12 y old girl was admitted 24 days after start a WHO multidrug therapy scheme for multibacillary leprosy (dapsone, clofazimine and rifampicin with intense jaundice, generalized lymphadenopathy, hepatoesplenomegaly, oral erosions, conjunctivitis, morbiliform rash and edema of face, ankles and hands. The main laboratory data on admission included: hemoglobin, 8.4 g/dL; WBC, 15,710 cells/mm³; platelet count, 100,000 cells/mm³; INR = 1.49; increased serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, direct and indirect bilirubin. Following, the clinical conditions had deteriorated, developing exfoliative dermatitis, shock, generalized edema, acute renal and hepatic failure, pancytopenia, intestinal bleeding, pneumonia, urinary tract infection and bacteremia, needing adrenergic drugs, replacement of fluids and blood product components, and antibiotics. Ten days after admission she started to improve, and was discharged to home at day 39th, after start new supervised treatment for leprosy with clofazimine and rifampicin, without adverse effects. This presentation fulfils the criteria for the diagnosis of dapsone hypersensitivity syndrome (fever, generalized lymphadenopathy, exfoliative rash, anemia and liver involvement with mixed hepatocellular and cholestatic features. Physicians, mainly in geographical areas with high prevalence rates of leprosy, should be aware to this severe, and probably not so rare, hypersensitivity reaction to dapsone.Menina, 12 anos, foi admitida referindo o uso de esquema de poliquimioterapia preconizado pela OMS para tratamento de hanseníase forma multicibacilar (dapsona, rifampicina e clofazimina há 24 dias, apresentando icterícia, linfadenomegalia generalizada, hepatoesplenomegalia, conjuntivite, úlceras orais, exantema morbiliforme e edema de face, mãos e tornozelo. Os principais achados laboratoriais à admissão incluíam: hemoglobina, 8,4 g

  1. Hepatitis C virus and human T-lymphotropic virus coinfection: epidemiological, clinical, laboratory and histopathological features Coinfecção vírus da hepatite C-vírus linfotrópico de células T humanas: aspectos epidemiológicos, clínicos, laboratoriais e histopatológicos

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    Flávio Augusto Pádua Milagres

    2009-08-01

    Full Text Available Twenty-four hepatitis C virus patients coinfected with human T-lymphotropic virus type 1 were compared with six coinfected with HTLV-2 and 55 with HCV alone, regarding clinical, epidemiological, laboratory and histopathological data. Fischer's discriminant analysis was applied to define functions capable of differentiating between the study groups (HCV, HCV/HTLV-1 and HCV/HTLV-2. The discriminant accuracy was evaluated by cross-validation. Alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with intravenous drug users were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported abdominal pain or a sexual partner with hepatitis. Coinfected patients presented higher platelet counts, but aminotransferase and gamma-glutamyl transpeptidase levels were higher among HCV-infected subjects. No significant difference between the groups was seen regarding liver histopathological findings. Through discriminant analysis, classification functions were defined, including sex, age group, intravenous drug use and sexual partner with hepatitis. Cross-validation revealed high discriminant accuracy for the HCV group.Compararam-se 24 pacientes coinfectados pelos vírus da hepatite C/vírus linfotrópico de células T humanas do tipo 1 com 6 coinfectados por VHC/HTLV-2 e 55 infectados pelo VHC, no tocante a dados clínico-epidemiológicos, laboratoriais e histopatológicos. A análise discriminante de Fischer foi utilizada para definir funções capazes de diferenciar os grupos de estudo (VHC, VHC/HTLV-1 e VHC/HTLV-2. A acurácia discriminatória foi avaliada pelo por validação cruzada. O uso de álcool, drogas endovenosas, cocaína inalatória e a parceria sexual com UDEV foram mais freqüentes no grupo VHC/HTLV-2, enquanto queixa de dor abdominal e parceiro sexual com hepatite predominaram no grupo VHC. Os coinfectados apresentaram número maior de plaquetas, enquanto as aminotransferases e

  2. Agomelatine in the treatment of mild-to-moderate depression in patients with cardiovascular disease: results of the national multicenter observational study PULSE

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    Medvedev VE

    2017-04-01

    Full Text Available Vladimir E Medvedev Department of Psychiatry, Psychotherapy and Psychosomatic Pathology, RUDN University, Moscow, Russia Background: PULSE was a large, observational, multicenter study designed to evaluate the efficacy and safety of agomelatine in the treatment of major depression in patients with cardiovascular disease (CVD.Methods: Patients with mild-to-moderate major depressive episodes, without psychotic symptoms, were treated as outpatients or in cardiac facilities in 46 regions of Russia. The patients received antidepressant monotherapy with agomelatine 25 or 50 mg, once daily, for 12 weeks.Results: The mean age of the patients (N=896 was 51.4±9.9 years, and 68.5% were women. A progressive improvement in the total score on both the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS, from 13.1±3.8 and 13.9±3.1 at baseline to 3.7±2.8 and 3.9±3.0, respectively, was observed by 12 weeks. All individual HADS scores improved rapidly; the change between visits was also significant (P<0.0001. The majority (84.6% were remitters (HADS total score <7 by 12 weeks. The Clinical Global Impression – Severity and Improvement scores also improved quickly. The mean hypochondria index (Whiteley Index decreased significantly from 48.0±11.8 at baseline to 25.2±9.2 at 12 weeks (P<0.0001. The main hemodynamic indices improved or remained stable, and biochemical parameters reflecting liver function (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, total bilirubin did not exceed three times the upper limits of established norms.Conclusion: Agomelatine resulted in statistically significant improvements in depressive symptoms, anxiety, and hypochondria in depressed patients with CVD, and had good tolerability. Our data suggest that agomelatine is safe to treat depression in patients with CVD. Keywords: depression, cardiovascular disease, agomelatine, anxiety

  3. Clinical features of patients developing primary hepatocellular carcinoma during anti-HBV therapy with nucleos(tide analogues

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    ZHANG Ying

    2017-04-01

    Full Text Available ObjectiveTo investigate the clinical features of patients developing hepatocellular carcinoma (HCC during anti-hepatitis B virus (HBV therapy with nucleos(tide analogues (NAs. MethodsA total of 542 patients who were diagnosed with HCC for the first time in The Third Affiliated Hospital of Sun Yat-Sen University from January 2008 to September 2014 were enrolled, and they all had chronic HBV infection. According to the presence or absence of standard therapy with NAs, they were divided into antiviral group (130 patients and non-antiviral group (412 patients. A retrospective analysis was performed for their clinical data, including age, sex, family history of tumor, duration of HBV infection, the time when a confirmed diagnosis of liver cirrhosis was made, history of drinking, history of diabetes, history of medication, laboratory parameters, liver pathology, and imaging findings, and these data were compared between the two groups. The t-test was used for comparison of normally distributed continuous data between groups, the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsCompared with the non-antiviral group, the antiviral group had significant increases in the proportion of patients with liver cirrhosis(90.0% vs 78.4%, χ2=8.528, P=0.003 and HBeAg-positive rate(29.4% vs 185%, χ2=6.794, P=0.009. There was a significant difference in the constitution of HBV DNA between the two groups (χ2=173.142, P<0.001, as well as significant differences in alanine aminotransferase, gamma-glutamyl transpeptidase, and alpha-fetoprotein (all P<0.001. Compared with the non-antiviral group, the antiviral group had a higher proportion of patients with early- or intermediate-stage liver cancer, smaller and fewer cancer lesions, and a lower proportion of patients with vascular invasion or distant metastasis (all P

  4. Analysis of influencing factors for short-term outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

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    ZHANG Xin

    2015-05-01

    Full Text Available ObjectiveTo investigate the effects of antiviral drugs, lamivudine (LAM and entecavir (ETV, on the short-term outcome in patients with hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF. MethodsThe demographic and clinical data of 445 patients with HBV-related ACLF (LAM∶ETV, 333∶112 who were hospitalized in the First Clinical Medical College of Fujian Medical University from January 2004 to December 2010 were collected, including age, sex, complications, clinical biochemical parameters, coagulation parameters, the use of antiviral drug, artificial liver treatment, and the survival at 24 weeks. The independent risk factors for the outcome at 24 weeks were determined by univariate and multivariate logistic regression analyses. ResultsThe univariate analysis indicated that the LAM group had significantly higher globulin, total bilirubin (TBil, alanine aminotransferase, international normalized ratio (INR, serum creatinine, and model for end-stage liver disease (MELD score than the ETV group (P<0.05, but had significantly lower cholinesterase and prothrombin time activity (PTA than the ETV group (P<0.05. The death group had significantly older age, higher incidence rates of liver cirrhosis, hepatic encephalopathy, spontaneous bacterial peritonitis, pulmonary infection, mycotic infection, electrolyte disturbance, hepatorenal syndrome, and upper gastrointestinal hemorrhage, and higher TBil, INR, white blood count, and MELD score than the survival group (P<0.05, but had significantly lower albumin, gamma-glutamyl transpeptidase, cholesterol, cholinesterase, serum sodium, PTA, alpha-fetoprotein, hemoglobin, platelet, and positive rate of HBeAg than the survival group (P<0.05. And there was no significant difference in the use of antiviral drugs (LAM∶ETV between the death group and the survival group (P=0.21. The multivariate logistic regression analysis showed that older age, hepatic encephalopathy, hepatorenal syndrome

  5. 自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的临床特点及诊断分析

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    LI Bing

    2014-05-01

    Full Text Available ObjectiveTo analyze the clinical features and laboratory test results of patients with autoimmune hepatitis (AIH-primary biliary cirrhosis (PBC overlap syndrome, as well as their correct diagnosis rate and time to diagnosis. MethodsFifty-three patients who were diagnosed by liver biopsy as having AIH-PBC overlap syndrome from January 2009 to June 2013 were selected as subjects; 53 AIH patients and 53 PBC patients were selected as control groups. Their clinical manifestations, laboratory test results, and diagnosis on admission were retrospectively analyzed. Comparison of normally distributed quantitative data between groups was made by one-way analysis of variance, and multiple comparisons were made by SNK-q test; comparison of qualitative data between groups was made using R×C contingency table, and multiple comparisons were made by Scheffe′s confidence interval test. ResultsThe 53 patients with AIH-PBC overlap syndrome had a serum alanine aminotransferase level of 173.65±52.08 U/L, a serum total bilirubin level of 38.07±6.82 μmol/L, a serum alkaline phosphatase (ALP level of 293.81±28.89 U/L, and a serum gamma-glutamyl transpeptidase level of 57.57±78.84 U/L. ALP showed significant difference between the patients with AIH-PBC overlap syndrome and control groups. The serum level of immunoglobulin M in overlap syndrome patients was 3.33±2.12 g/L, which was significantly different from those of two control groups. Of the 53 overlap syndrome patients, 27 were positive for anti-mitochondrial antibody-M2, and the positive rate was significantly different from those of two control groups. Without liver biopsy, the correct diagnosis rate was the lowest (52.83%, and it took the longest time (8±7.7 d to confirm the diagnosis on admission. ConclusionThe clinical manifestations of patients with AIH-PBC overlap syndrome are more similar to those of PBC patients, but their biochemical test results are more similar to those of AIH patients. AIH

  6. Non-alcoholic fatty liver disease in diabetics--prevalence and predictive factors in a multiracial hospital clinic population in Malaysia.

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    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 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 Pty Ltd.

  7. Relationship between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and disturbance of intermediary metabolism in the Long-Evans rat

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    Fan, F. (Dept. of Pharmacology, Toxicology and Therapeutics, Univ. of Kansas Medical Center, Kansas City, KS (United States)); Rozman, K.K. (Section of Environmental Toxicology, GSF-Inst. fuer Toxikologie, Neuherberg (Germany))

    1994-12-01

    The aim of this study was to examine the acute toxicity of TCDD in a rat strain other than the Sprague-Dawley (S-D) rat. Doses for the biochemical study were selected based on an acute range-finding study, which indicated that Long-Evans (L-E) rats are somewhat less susceptible to TCDD toxicity than are S-D rats. Male L-E rats were dosed orally with 10, 20, 45, 67, 100 and 150 [mu]g/kg TCDD. Body weight and feed intake were dose-dependently decreased prior to killing of the animals. Eight days after dosing, animals were killed and tryptophan, total T[sub 4] (TT[sub 4]) and total T[sub 3] (TT[sub 3]) levels were determined in serum, whereas the activities of ethoxy-resorufin-O-deethylase (EROD), phosphoenolpyruvate carboxykinase (PEPCK), [gamma]-glutamyl transpeptidase ([gamma]-GT) and tryptophan 2,3-dioxygenase (TdO) were measured in liver. EROD activity was fully induced at all doses studied, indicating that as in S-D rats, Ah-receptor-mediated effects do not seem to play any major role in the acute toxicity of TCDD in this rat strain either. Hepatic PEPCK activity was dose-dependently decreased in a similar dose range as in S-D rats, indicating inhibition of gluconeogenesis. Feed intake was dose-dependently decreased as a result of a dose-dependent elevation in serum tryptophan levels, which in turn were related to reduced liver TdO activity. Hepatic [gamma]-GT activity was also dose-dependently reduced. However, unlike in S-D rats, these dose-responses occurred in a higher dose range than the reduction of PEPCK activity which appears to be the explanation for the decreased susceptibility of L-E rats to TCDD. Serum TT[sub 4] levels were significantly decreased at all doses, whereas the serum concentration of TT[sub 3] appeared unaffected. The results of this study suggest that subtle differences in the regulation of intermediary metabolism between these two strains of rats are responsible for strain differences in the susceptibility to TCDD. (orig.)

  8. Risk factors that affect reproductive target achievement in fertile dairy cows.

    Science.gov (United States)

    Aungier, S P M; Roche, J F; Diskin, M G; Crowe, M A

    2014-01-01

    The aims of the present study were to investigate (1) the risk factors that influence the achievement of reproductive targets postpartum (pp) and (2) the key factors that influence pregnancy rate following first artificial insemination (AI) in dairy cows. Ninety-eight Holstein-Friesian pp cows were blood sampled from wk 1 to 4 pp for hematology and biochemistry. Reproductive tract health was assessed weekly by ultrasonography and vaginal mucus scoring. Body condition score (BCS), lameness score, and milk yield were assessed every 2 wk. Milk samples for progesterone assay were collected twice weekly and on d 4, 5, and 7 after AI. Risk factors associated with achieving reproductive targets depended on (1) increased metabolic activity of the liver (increased glutamate dehydrogenase at calving and increased γ-glutamyl transpeptidase in wk 4), (2) a competent immune system (increased neutrophils in wk 1; decreased α1-acid glycoprotein in wk 1, 2, and 3), (3) an endocrine system that was capable of responding by producing sufficient triiodothyronine in wk 2 and increased insulin-like growth factor I in wk 3 and 4, (4) a lower negative energy balance status (decreased nonesterified fatty acid concentration in wk 1; decreased β-hydroxybutyrate concentration in wk 2; BCS loss between calving and d 28 pp mucus discharge at first ovulation and at d 45 pp; resumed ovarian cyclicity by the end of the voluntary waiting period (≥ d 35 pp)], and (6) adequate diet (to ensure increased glutathione peroxidase in wk 2 and 3 and increased magnesium in wk 4). Risk factors that increased the odds of a successful first AI were previous ovulation(s) (odds ratio=3.17 per ovulation), BCS >2.5 at AI (odds ratio=3.01), and clear vaginal mucus (score=0) compared with purulent mucus (score >0) 4 d after first AI (odds ratio=2.99). In conclusion, this study identified key risk factors in the early pp period that give a higher probability of cows achieving their reproductive targets and of

  9. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.

    Science.gov (United States)

    Kowdley, Kris V; Luketic, Velimir; Chapman, Roger; Hirschfield, Gideon M; Poupon, Raoul; Schramm, Christoph; Vincent, Catherine; Rust, Christian; Parés, Albert; Mason, Andrew; Marschall, Hanns-Ulrich; Shapiro, David; Adorini, Luciano; Sciacca, Cathi; Beecher-Jones, Tessa; Böhm, Olaf; Pencek, Richard; Jones, David

    2018-05-01

    Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus. OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2018;67:1890-1902). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

  10. Clinical features of type 1 autoimmune pancreatitis: an analysis of 13 cases

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    MO Xue

    2018-03-01

    Full Text Available ObjectiveTo investigate the clinical features of type 1 autoimmune pancreatitis (AIP, and to deepen the understanding of this disease, reduce false positive rate, and enhance people′s awareness of this disease. MethodsA retrospective analysis was performed for the clinical data of 13 patients with type 1 AIP who were admitted to The First Hospital of Jilin University from January 2012 to December 2016, including general status, clinical manifestations, laboratory serological examination, imaging findings, histopathological findings, treatment, and prognosis. ResultsOf all 13 patients, there were 9 male and 4 female patients with a mean age of 60.08±9.47 years. Major clinical manifestations included jaundice (69.2%, abdominal pain (61.5%, and weight loss (61.5%. The most common organ involved was bile duct (462%, and 30.8% of the patients had sclerosing cholangitis. Of all patients, 23.1% had diabetes. As for serological markers, 92.30% patients had more than 2 times increase in IgG4, and 7.69% had 1-2 times increase in IgG4, 53.85% patients had an increase in CA19-9, 69.23% patients had an increase in total bilirubin, more than two thirds of the patients had an increase in aminotransferases or gamma-glutamyl transpeptidase. As for imaging findings, 53.8% patients had diffuse enlargement of the pancreas on CT, 46.2% had focal enlargement of the pancreas, and 46.2% patients had low-density cyst-like shadow in pancreatic lesions. Pathological examination showed fibrous connective tissue proliferation with infiltration of lymphocytes and plasma cells. All patients were given standard glucocorticoid therapy (initial dose of prednisone: 30-40 mg/d and the remission rate of glucocorticoid therapy was 100%. The follow-up time was 12 months, and one patient experienced multiple recurrences in the course of the disease. ConclusionType 1 AIP is the local manifestation of IgG4-associated disease in the pancreas, which often occurs in middle-aged and

  11. Adipocytokines, hepatic and inflammatory biomarkers and incidence of type 2 diabetes. the CoLaus study.

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    Pedro Marques-Vidal

    Full Text Available CONTEXT: There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein - CRP; interleukin-1beta - IL-1β; interleukin-6- IL-6; tumour necrosis factor-α - TNF-α; leptin and adiponectin and gamma-glutamyl transpeptidase (γGT on the incidence of type 2 diabetes. METHODS: Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years, followed for an average of 5.5 years (2003-2008. The endpoint was the occurrence of type 2 diabetes. RESULTS: 208 participants (5.4%, 66 women developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval: 0.97 (0.64-1.47, 0.84 (0.55-1.30 and 0.64 (0.40-1.03 for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05. Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed variables or when gender-specific quartiles were used. CONCLUSION: Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little

  12. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.

    Science.gov (United States)

    Kargiotis, Konstantinos; Athyros, Vasilios G; Giouleme, Olga; Katsiki, Niki; Katsiki, Evangelia; Anagnostis, Panagiotis; Boutari, Chrysoula; Doumas, Michael; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2015-07-07

    To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH. This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values. The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20(th), which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3(rd) treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6(th) treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3(rd) treatment month. No patient had MetS by the 9(th) treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should

  13. Characterization of guinea pig myocardial leukotriene C4 binding sites. Regulation by cations and sulfhydryl-directed reagents

    International Nuclear Information System (INIS)

    Hogaboom, G.K.; Mong, S.; Stadel, J.M.; Crooke, S.T.

    1985-01-01

    Using [ 3 H]leukotriene C4 (LTC4) and radioligand-binding techniques, specific leukotriene C4 binding sites have been identified in membranes derived from guinea pig ventricular myocardium. High performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-serine-borate (80 mM), less than 2% of membrane-bound [ 3 H]LTC4 was converted at 20 degrees to [ 3 H]leukotriene D4 or [ 3 H]leukotriene E4. The specific binding of 4 nM [ 3 H]LTC4, in the presence of 80 mM L-serine-borate, reached a stable steady state within 15 min at 20 degrees (pH 7.5). A monophasic Scatchard plot of saturation binding data yielded a dissociation constant (Kd) of 27.5 +/- 6.0 nM and a maximum number of binding sites (Bmax) of 19.9 +/- 5.2 pmol/mg of membrane protein. Competition binding studies of [ 3 H]LTC4 with synthetic leukotriene C4, leukotriene D4, and leukotriene E4 and the putative peptidoleukotriene antagonists FPL 55712, SKF 88046, and 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid revealed an order of potency of leukotriene C4 much greater than 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid greater than SKF 88046 greater than LTE4 greater than LTD4 greater than FPL 55712. The specific [ 3 H]LTC4 binding was stimulated by the divalent cations Ca2+, Mg2+, and Mn2+ and to a lesser degree by the monovalent cations Na+, K+, Li+, and NH4+. CaCl2 (3 mM) and NaCl (150 mM) stimulated the LTC4 binding by increasing the Bmax to 42.6 +/- 5.9 and 35.0 +/- 2.0 pmol/mg, respectively, but had minimal effects on Kd

  14. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

    1982-01-01

    The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED 50 dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and γ-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED 50 dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair

  15. Clinical impact of non-organ-specific autoantibodies on the response to combined antiviral treatment in patients with hepatitis C.

    Science.gov (United States)

    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

  16. Ticlopidine-induced cholestatic hepatitis: A case report and review of the literature

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    Luigi Anastasio

    2012-10-01

    Full Text Available Introduction Cholestatic hepatitis is frequently a drug-related syndrome. We describe the case of a 57-year-old man who developed cholestatic hepatitis two months after starting therapy with ticlopidine following a carotid endarterectomy.Materials and methods The patient presented with anorexia, nausea, and dark-colored urine. The work-up included laboratory tests and imaging studies of the liver (ultrasound and magnetic resonance imaging. The authors analyze the case using the scale developed by Maria and Victorino for the diagnosis of drug-induced hepatitis, the Naranjo algorithm for adverse drug reactions, and the RUCAM algorithm for causality assessment of hepatotoxicity. They also review data from the MedLine database on cases of ticlopidine-induced cholestatic hepatitis reported during the period 1982–2011.Results Bilirubin, aminotransferases, alkaline phosphatases, and gamma glutamyl transpeptidase levels were elevated at admission and progressively declined after ticlopidine was discontinued. The absence of biliary obstruction at ultrasonography and magnetic resonance cholangiography, the negative results of viral and immunologic tests, and the resolution of the syndrome after discontinuation of the drug all suggested ticlopidine-induced hepatotoxicity. The assessment of this case with toxicity algorithms confirmed that a causal link to ticlopidine was “probable” or “highly probable.” The patient was treated with ursodesoxycholic acid, clopidogrel (75 mg/day, and (after the laboratory parameters had normalized rosuvastatin (10 mg/day. No further clinical and laboratory abnormalities have been observed during two month follow-up.Discussion The toxicity of ticlopidine is well established: our review revealed reports of 57 cases of ticlopidine-induced cholestatic hepatitis during the period 1982–2011. The mechanisms underlying the toxic effects of this drug are not clear, but they are probably related to the chemical structure

  17. Hypocalcaemia after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Vliet, Esther I. van; Kam, Boen L.R.; Teunissen, Jaap J.M.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus MC, University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Zillikens, M.C.; Peeters, Robin P. [Erasmus MC, University Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus MC, University Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2013-12-15

    The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D{sub 3}, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 {+-} 0.01 to 2.26 {+-} 0.02 mmol/l, p = 0.02). Eight patients (17 %) showed a marked decrease in serum calcium levels with a nadir of {<=}2.10 mmol/l. In five patients (11 %), calcium substitution therapy was prescribed. PTH increased significantly (5.9 {+-} 0.6 to 6.7 {+-} 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 {+-} 3 to 77 {+-} 3 {mu}mol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 {+-} 0.01 at baseline to a nadir of 2.24 {+-} 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22 %) showed a serum calcium nadir of {<=}2.10 mmol/l, and 11

  18. Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue

    International Nuclear Information System (INIS)

    Ida, Tomoyo; Suzuki, Hideyuki; Fukuyama, Keiichi; Hiratake, Jun; Wada, Kei

    2014-01-01

    The binding modes of acivicin, a classical and an electrophilic active-site-directed glutamate analogue, to bacterial γ-glutamyltranspeptidases were found to be diverse. γ-Glutamyltranspeptidase (GGT) is an enzyme that plays a central role in glutathione metabolism, and acivicin is a classical inhibitor of GGT. Here, the structure of acivicin bound to Bacillus subtilis GGT determined by X-ray crystallography to 1.8 Å resolution is presented, in which it binds to the active site in a similar manner to that in Helicobacter pylori GGT, but in a different binding mode to that in Escherichia coli GGT. In B. subtilis GGT, acivicin is bound covalently through its C3 atom with sp 2 hybridization to Thr403 O γ , the catalytic nucleophile of the enzyme. The results show that acivicin-binding sites are common, but the binding manners and orientations of its five-membered dihydroisoxazole ring are diverse in the binding pockets of GGTs

  19. Detection of mesocarp oleoyl-thioesterase gene of the South ...

    African Journals Online (AJOL)

    Administrator

    TAT CCA ACT TGG GGT GAT GTT GTT GAG ATT GAA ACA TGG TGC CAA GGG 48. Y P T W G D V V E I E T W C G G 16. GAA GGA AGA ATA GGC ACC AGG CGT GAT TGG ATT ATC AAG GAT TTG GCT 96. E G R I G T R R D W I I K D L A 32. ACT GGT GAA GTT ATT GGT AGA GCC ...

  20. ZINC LEVELS IN WEANED PIGLETS DIET ON BLOOD PARAMETERS PROFILE NÍVEIS DE ZINCO NA DIETA DE LEITÕES RECÉM-DESMAMADOS SOBRE O PERFIL DE PARÂMETROS SANGÜÍNEOS

    Directory of Open Access Journals (Sweden)

    Alessandro Luís Fraga

    2007-07-01

    Full Text Available The present experiment was conducted to determine if the addition of different levels of zinc (0, 1,500, 3,000 and 4,500 ppm in piglets diets, influences blood profile (calcium, copper, iron, zinc, hemoglobin (Hb, hematocrit (Ht, serum total protein (STP, albumin (ALB and globulin (GLOB, alkaline phosphatase (AP, aspartate aminotransferase (ASP, alanine aminotransferase (ALT and gamma-glutamyl transferase (GGT serum activity. Sixty weaned piglets (21 days of age, castrated males, crossed, from multisite production were used, arranged in a randomized design, with 4 traits, divided in 5 similar groups, within respective periods: Period 1 (P1, of the it weans (day zero up to 14 days it after weaning; Period 2 (P2, from 15 to 42 days after weaning and Total Period (TP, of the it weans to the 42 days after weaning. The collections of blood were made to the 0, 7, 14, 21 and 42 days after weaning. The addition of 4,500 ppm of Zn fed 2 weeks post-weaning reached high Zn serum levels. Blood profiles were affected by collect day. KEY-WORDS: Swine, weaned piglets, zinc oxide. adição de diferentes níveis (0, 1.500, 3.000 e 4.500 ppm de zinco (utilizando como fonte o ZnO na dieta de leitões influencia o perfil de parâmetros sangüíneos (cálcio, cobre, ferro, zinco, hemoglobina (Hb, hematócrito (Ht, proteínas séricas totais (PST, albumina (ALB, globulina (GLOB e atividade enzimática sérica de fosfatase alcalina (FA, aspartato aminotransferase (ASP, alanina aminotransferase (ALT e gama glutamil transferase (GGT. Utilizaram-se sessenta leitões machos castrados, mestiços, desmamados aos 21 dias de idade, procedentes de sistema de criação em sítios separados, dentro dos períodos: Período 1 (P1, do desmame (dia zero até 14 dias pós-desmame; Período 2 (P2, de 15 a 42 dias pós-desmame e Período Total (PT, do desmame aos 42 dias pós-desmame. As coletas de sangue foram efetuadas aos 0, 7, 14, 21 e 42 dias pós-desmame. Utilizou-se o DIC, num

  1. Comparative transcriptome profiling of the early infection of wheat roots by Gaeumannomyces graminis var. tritici.

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    Lirong Yang

    Full Text Available Take-all, which is caused by the fungal pathogen, Gaeumannomyces graminis var. tritici (Ggt, is an important soil-borne root rot disease of wheat occurring worldwide. However, the genetic basis of Ggt pathogenicity remains unclear. In this study, transcriptome sequencing for Ggt in axenic culture and Ggt-infected wheat roots was performed using Illumina paired-end sequencing. Approximately 2.62 and 7.76 Gb of clean reads were obtained, and 87% and 63% of the total reads were mapped to the Ggt genome for RNA extracted from Ggt in culture and infected roots, respectively. A total of 3,258 differentially expressed genes (DEGs were identified with 2,107 (65% being 2-fold up-regulated and 1,151 (35% being 2-fold down-regulated between Ggt in culture and Ggt in infected wheat roots. Annotation of these DEGs revealed that many were associated with possible Ggt pathogenicity factors, such as genes for guanine nucleotide-binding protein alpha-2 subunit, cellulase, pectinase, xylanase, glucosidase, aspartic protease and gentisate 1, 2-dioxygenase. Twelve DEGs were analyzed for expression by qRT-PCR, and could be generally divided into those with high expression only early in infection, only late in infection and those that gradually increasing expression over time as root rot developed. This indicates that these possible pathogenicity factors may play roles during different stages of the interaction, such as signaling, plant cell wall degradation and responses to plant defense compounds. This is the first study to compare the transcriptomes of Ggt growing saprophytically in axenic cultures to it growing parasitically in infected wheat roots. As a result, new candidate pathogenicity factors have been identified, which can be further examined by gene knock-outs and other methods to assess their true role in the ability of Ggt to infect roots.

  2. INFLAMMATORY MARKERS IN ACUTE ISCHAEMIC STROKE IN RELATION TO CLINICAL SEVERITY AND EARLY OUTCOME

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    S. Gopi

    2018-01-01

    Full Text Available BACKGROUND Biochemical markers of inflammation could be useful to predict severity of stroke in acute phase. Stroke is the third cause of mortality and the first cause of disability. Recent literature have demonstrated that inflammation contributes to all phases of atherosclerosis. The results of researchers suggest that atherosclerosis is an inflammatory disease. The aim of the study is to assess the1. Level of peripheral inflammatory markers in acute ischaemic stroke and their relation to severity of acute stroke. 2. Value of inflammatory markers in predicting the short-term outcome and disability at the end of six months. MATERIALS AND METHODS This is a prospective case control study for 6 months done from September 2014 to August 2016 in 100 patients of acute ischaemic stroke within first 5 days of symptom onset in comparison >18 years of age with 50 age and sex matched controls. Blood samples for all cases and controls were sent for erythrocyte sedimentation rate, Neutrophil-to-Lymphocyte Ratio (NLR, hs-C-reactive protein, mean platelet volume, serum ferritin, serum albumin and S. gamma-glutamyl transferase at admission. RESULTS The mean values of ESR, NLR, hs-CRP in all the cases are higher when compared to the controls and are statistically significant, whereas the mean values of MPV, S. ferritin, S. albumin and GGT in cases are lower when compared to controls, but are within normal range and difference is statistically significant except ferritin. ESR, hs-CRP has significant correlation with severity of acute ischaemic stroke. The mean values of these markers increased with increase in severity. Serum albumin has significant correlation with severity of acute ischaemic stroke with mean values of these markers decreasing with increase in severity of stroke. There is no significant correlation of the inflammatory markers in present study with the short-term outcome. CONCLUSION Inflammation plays an important role in the pathogenesis of non

  3. Protective Role of Emodin in Reducing The Gamma Rays Induced Hazardous Effects On The Tongue of Diabetic or Normoglycaemic Mice

    International Nuclear Information System (INIS)

    Haggag, M.G.; Kazem, H.H.

    2013-01-01

    Ionizing radiation leads to damage at various cellular and sub-cellular levels and can be prevented by radio protectors. There is a need for natural prospective radio protectors that protect normal tissues from ionizing radiation in patients receiving high doses of radiation for treating malignant neoplasms. The study aimed to evaluate the potential protective role of emodin in reducing the severity of gamma rays-induced hazardous damage in the tongue of normoglycaemic and diabetic mice. Sixty-four male mice were randomly divided into 8 experimental groups: control group received vehicle, emodin group received daily emodin dose of 4g/kg orally for a week, diabetes mellitus (DM) group in which DM was induced by streptozotocin (STZ) treatment, emodin + DM received emodin for a week + STZ treatment, irradiated group submitted to 4 Gy of gamma rays and received vehicle for a week, gamma rays + DM group received gamma rays + STZ treatment, gamma rays + emodin group received gamma rays + emodin for a week, and gamma rays + DM + emodin group received gamma rays + STZ treatment + emodin for a week. Tongue and serum of mice were biochemically examined for screening gamma radiation and diabetic damages and the efficacy of emodin in ameliorating these damaging effects. The levels of cellular thiols such as reduced glutathione (GSH), oxidized glutathione (GSSG), total thiols (TT) and lipid peroxidation products; malondialdehyde (MDA) and conjugated dienes (CD), were assessed in tongue tissues. Tongue antioxidant enzymes; gamma glutamyl transferase (GGT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glucose-6-phosphatase (G-6-P), were measured and serum glucose level was estimated. The results revealed alterations of the levels of cellular thiols and antioxidant enzymes in tongue and the level of glucose in serum of gamma irradiated diabetic mice were ameliorated in mice groups received emodin treatment. The results suggest that emodin treatment (4 g

  4. The Protective Efficacy Of Extract Of Hibiscus Sabdariffa (Karkade) Calyces Against Alcohol Toxicity In Male Albino Rats

    International Nuclear Information System (INIS)

    Ali, E.A.; Ali, E.A.; Shahen, E.M.; El Madawy, S.A.

    2013-01-01

    Hibiscus sabdariffa (HS), Malvacea family, is a medicinal plant with a worldwide fame. Its benefit effect on some physiological parameters as blood picture, blood pressure, fasting blood sugar, lipid profile, liver and kidney functions, electrolytes and antioxidant capacity is mentioned in several recent studies. The purpose of this study was to assess the efficacy of this plant in protecting from alcohol toxicity in rats. Thirty two adult male albino rats were divided into four equal groups: group 1 received water orally for 30 days, group 2 received ethanol (5 ml/kg/day) for 30 days, both group 3 and group 4 received Hibiscus sabdariffa (100 mg/kg/day) orally for 30 days and then group 4 received ethanol (5 ml/kg/day) orally for another 30 days. Serum hepatic markers (aspartate and alanine minotransferases; AST and ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) were increased significantly by alcohol abuse with no observed improvement in treatment with HS. Significant reduction in total protein and albumin was observed in alcohol abuse which improved with HS treatment and showed significant increase as compared with both control and alcohol treated groups. Serum kidney markers (urea, creatinine and uric acid) were increased in alcohol abuse and only creatinine and uric acid nearly returned to normal levels with HS treatment while urea level remains high. Serum glucose was increased significantly in alcohol abuse and significantly decreased in group 3 (HS treated) and group 4 (HS + ethanol). Serum total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and atherogenic index were increased significantly while HDL-C was significantly reduced in alcohol abuse. HS treatment resulted in significant increase in HDL-C and therefore decreased atherogenic index in both group 3 and group 4 which indicated protective effect of HS for coronary heart diseases. These results lead to the

  5. [Effect of recombinant human growth hormone therapy on metabolic parameters in patients with craniopharyngioma].

    Science.gov (United States)

    Mao, J F; Wang, X; Xiong, S Y; Zheng, J J; Yu, B Q; Nie, M; Wu, X Y; Qi, S T

    2017-11-14

    Objective: To investigate the effects of recombinant human growth hormone (rhGH) on metabolic parameters in patients with craniopharyngioma surgeries. Methods: Totallys 30 patients with craniopharyngioma were included in this retrospective study. They were divided into growth hormone (GH) group and control group according to whether they received rhGH therapy or not. The following parameters, including body mass index (BMI), weight, waist circumstance, transaminase, fasting blood glucose, lipid profile and high-sensitivity C-reactive protein (hsCRP) were compared after rhGH therapy for 4-6 months. Results: In GH group, patients were 18-46 (30.0±8.8) years old. The duration after craniopharyngioma surgery was (12.9±5.4) years. Before rhGH therapy, they had got sufficient thyroid and glucocorticoid hormone replacement. After rhGH therapy, the body weight decreased from (92.3±20.1) to (87.6 ±14.6) kg ( P =0.190), with a reduction of BMI from (30.1±5.9) to (28.2±3.7) kg/m(2) ( P =0.120). The waist circumference decreased from (104.4±9.4) cm to (98.8±10.6) cm ( P =0.002). Alanine aminotransferase (ALT) decreased from (52±34) to (28±19) U/L ( P =0.029), with a reduction of aspartate transaminase (AST) from (46±21) to (33±18) U/L ( P =0.035) and γ-glutamyl transpeptadase (GGT) from (59±42) to (29±15) U/L ( P =0.02). hsCRP decreased from (5.3±4.9) to (2.3±2.8) mg/L ( P =0.006) and triglyceride (TG) decreased from (1.8±0.7) to (1.5±0.6) mmol/L ( P =0.028). Fasting blood glucose, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and free fat acid (FFA) were not significantly changed(all P >0.05). In the control group, the above mentioned parameters did not changed significantly during 4-6 months of observational period(all P >0.05). Conclusion: rhGH therapy improves metabolic parameters in patients after craniopharyngioma surgery by decreasing body weight, waist circumstance and fat deposit in liver, as well as

  6. Effects of the Sequence of Isocaloric Meals with Different Protein Contents on Plasma Biochemical Indexes in Pigs.

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    Chunyan Xie

    Full Text Available Nutrient composition and pattern of food intake may play a significant role in weight gain. The aim of this study was to document the effects of a daily 3-meal pattern with isocaloric diets containing different dietary protein contents on growth performance and different plasma biochemical indexes including amino acid plasma concentration in castrated male pigs. Then, 21 DLY (Duroc×Landrace×Yorkshire pigs aged 60 days were assigned randomly into 3 groups: a control group (crude protein, CP 18.1%, a group receiving high then basal and then low CP meals (High-Low group and a group receiving low then basal and then high CP meal (Low-High group for 40 days with pigs being feed-restricted. On day 40, after 12 h fasting, blood samples were obtained for analysis. The results showed that the insulin/glucagon ratio was lower in the High-Low group (P<0.05 when compared with the control group. Compared with the control group, the average daily gain of pigs from the High-Low group increased by 14.10% (P = 0.046. Compared with the control group, serum gamma-glutamyl transferase (GGT decreased significantly (P<0.05 in both the High-Low and Low-High groups. Plasma concentrations of branched-chain amino acids (BCAA: valine, isoleucine and leucine increased in the Low-High group (P<0.05 when compared with the control group; and plasma methionine and serine decreased in both the two experimental groups (P<0.05. Compared with the High-Low group, all the BCAA increased significantly (P<0.05 in the Low-High group. These findings suggest that the sequence and quantity of alimentary protein intake affect the insulin/glucagon ratio, as well as amino acid concentrations including BCAA, methionine and serine. It is proposed that meal pattern with pigs receiving high then basal and then low CP meals daily may help to improve the weight gain of pigs.

  7. Clinical management of parasitic gastroenteritis (PGE concurrent with moderate pneumonia in a goat: a clinical veterinary case report

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    Faez Firdaus Abdullah Jesse

    2017-09-01

    Materials and methods: The Jamnapari cross goat aged two years and weighing 40 Kg was presented to the Universiti Veterinary Hospital, Universiti Putra Malaysia with the history of diarrhea and depression. The goat was examined physically. Blood and fecal samples were collected for complete blood count, serum biochemistry analysis and parasitological examination. Standard treatment plan was applied for the correction of the the problem. Results: Physical examination findings revealed the goat was in poor body condition, dull and depressed. Wet and dry fecal traces were observed around the groin region. The temperature was slightly elevated (39.5°C, the heart rate was increased (160 b/min while other parameters were within normal range. Upon auscultation of the thoracic region, moderate crackle lung sound was determined. Visual observation of the nasal cavity indicated a bilateral mucopurulent nasal discharge. The hemogram result revealed evidence of a normocytic normochromic anemia, leukocytosis, neutrophilia with left shift and monocytosis. Serum biochemistry revealed increases in gamma-glutamyl transferase (GGT, sodium, chloride, creatine kinase (CK, and hyperglobulinemia. Fecal examination revealed increased in Strongyle egg count of about 2,700 eggs per gram of feces using the Modified Mcmaster technique. From the history, physical examination and laboratory findings the goat was diagnosed with clinical parasitic gastroenteritis (PGE concurrent with moderate pneumonia infection. The therapeutic plan for this case were 45 mL of kaolin-pectin (30 mL/Kg body weight orally SID for 3 days as anti-diarrhea, 12 mL Levamisole (12 mg/Kg bwt was administered orally once as anthelminthic, fluid therapy was instituted using 1.5 L of Lactated Ringers’ solution once via intravenously. Trimethoprim-Sulfamethoxazole (1 mL/16 Kg bwt was administered intramuscularly SID for 3 days. Conclusion: Follow up examination of the goat a week post treatment indicated a good prognosis

  8. Peculiarities of Liver Affection in Children with Infectious Mononucleosis

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    T.V. Sorokman

    2016-04-01

    Full Text Available Introduction. Today, there is a tendency of infectious mononucleosis (IM morbidity to spread. Aim of research is to identify clinical features of liver affection in children with infectious mononucleosis. Materials and methods. Case histories of 42 children aged from 4 to 15 years old with a diagnosis of chronic hepatitis were analyzed. The activity of alanine aminotransferase (ALT and aspartate aminotransferase (AST, levels of bilirubin, alkaline phosphatase (ALP, gamma-glutamyl (GGT, markers of viral hepatitis were determined. There were performed ultrasound investigation and enzyme immunoassay (IEA with determination of blood markers of Epstein — Barr virus (EBV (IgM VCA, IgG EA, IgG VCA, avidity and cytomegalovirus (CMV (IgM, IgG, avidity; EBV-DNA, CMV-DNA were defined by polymerase chain reaction. Depending on the etiology of the disease patients were divided into 3 groups: group 1 — patients with IM of EBV-etiology (17 patients; group 2 — patients with MI of CMV etiology (16 patients; group 3 — mixed IM of EBV + CMV etiology (9 patients. Received digital data were processed by methods of statistical analysis in application «Statistica‑6». Results. In 85.7 % of cases MI had usual course and moderate severity (enlargement of the lymph nodes was noted in 98.6 % of patients, tonsillitis throat — in 54.7 %, hepatomegaly — in 71.4 %, splenomegaly — in 38.1 %. The most common hemogram changes in MI are leukocytosis (64.2 % and atypical mononuclear cells (73.5 % 15 children (35.7 % had enhanced transaminase level. Icteric hepatitis was observed in five patients. Blood level of atypical mononuclear cells over 20 % was observed in 43.3 % of cases. Ultrasound investigation showed diffuse increase in liver echoicity in 36.6 % of patients. Conclusions. Hepatitis with MI was observed in more than half of patients, its development and severity correlated with etiological features of the disease (mixed infection

  9. [The relevance of the trace elements zinc and iron in the milk fever disease of cattle].

    Science.gov (United States)

    Heilig, M; Bäuml, D; Fürll, M

    2014-01-01

    The aim of this study was to analyse the concentrations of Zn and Fe as well as their relationships to metabolic parameters in milk fever cows. A total of 195 Simmental cows, downer cows and clinically healthy control animals were divided into five groups: a) control group (CG, n = 21), b) all cows with milk fever (MF) (n = 174), c) MF cows without additional diseases (n = 145), d) cows with MF and mastitis (n = 10) and e) cows with retained placenta or endometritis (n = 19). Selenium (Se), zinc (Zn), iron (Fe), calcium (Ca), inorganic phosphorus (Pi), tumour necrosis factor α (TNFα), haptoglobin (Hp), antioxidants (Trolox Equivalent Antioxidative Capacity: TEAC), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), bilirubin, urea, creatinine, glucose, cholesterol, gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were analysed in the blood serum. The concentrations of Zn, Fe, Ca, Pi and TEAC were lower in groups b) to e) whereas Hp was higher than in the CG (p ≤ 0.05). In group c), lower Ca and Pi concentrations were found when compared to groups d) and e) (p ≤ 0.05). In group e), Zn concentrations were significantly lower than in group c) (p ≤ 0.05). Zn was negatively correlated with K (CG) and positively correlated with TEAC, Cu, Mn and Fe (groups b and c) and with Mn (group e) (p ≤ 0.05). Fe was positively correlated with Ca (group c), Pi (group c), K (groups b and c) and Mg (groups b-d) as well as with Zn, Cu and Se (groups b and c) (p ≤ 0.05). In groups b) and c), TNFα was increased and negatively correlated with Fe (p ≤ 0.05). AP activity in groups b) and e) was lower than in the CG (p ≤ 0.05). These results and literature data support the hypothesis that Zn and Fe could be engaged in bone metabolism and be involved in the pathogenesis of MF. The concentrations of Hp and TEAC support this interpretation. Control of the Zn and Fe status of cows and Zn supplementation should be included in the

  10. Liver morphology and morphometry and plasma biochemical parameters of Wistar rats that received leaf infusion of Rudgea viburnoides Benth. (Rubiaceae

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    Juliana Castro Monteiro

    2009-04-01

    Full Text Available Rudgea viburnoides leaves are widely used in popular Brazilian medicine as a diuretic, antirheumatic, hypotensive and blood depurative tea. The present study was carried out to investigate the effects of this infusion on the liver and on the plasma biochemical parameters of Wistar rats. Two groups received the R. viburnoides leaf infusion at a daily dose of 10 or 20g dry-leaves/L water, during 40 days. The histopathological analysis did not show degenerated areas or infiltration of leucocytes. Hepatic morphometry showed accumulation of fat in the hepatocytes of the treated groups. There was no significant change in the plasma levels of urea, creatinin, uric acid, direct bilirubin, cholesterol, total proteins, albumin, gamma glutamyl tranferase (gamma-GT, alanine transaminase (ALT, aspartate transaminase (AST, chlorine, phosphate and calcium. A significant reduction in the plasma levels of triacylglycerol (TAG occurred in the group that received the higher dose.As folhas de Rudgea viburnoides Benth. são utilizadas na medicina popular como diuréticas, hipotensoras, anti-reumáticas, depurativas do sangue e em regimes de emagrecimento. O presente estudo foi delineado para avaliar o efeito da infusão das folhas de R. viburnoides nos parâmetros bioquímicos plasmáticos e na morfologia e morfometria hepática de ratos Wistar adultos. Dois grupos receberam a infusão das folhas, diariamente, nas dosagens de 10 e 20 g de folhas secas/L de água, durante 40 dias. O grupo controle recebeu a mesma quantidade de água. As análises histopatológicas não mostraram áreas degeneradas e infiltrados inflamatórios. A morfometria hepática mostrou acúmulo significativo de gordura nos hepatócitos dos animais tratados, principalmente no grupo que recebeu a maior dose da infusão (8,75% de gotículas lipídicas, comparado com 0,25% delas encontradas nos animais controles. Não foram observadas alterações nos níveis plasmáticos de uréia, creatinina,

  11. Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health*

    Science.gov (United States)

    Reiding, Karli R.; Ruhaak, L. Renee; Uh, Hae-Won; el Bouhaddani, Said; van den Akker, Erik B.; Plomp, Rosina; McDonnell, Liam A.; Houwing-Duistermaat, Jeanine J.; Slagboom, P. Eline; Beekman, Marian; Wuhrer, Manfred

    2017-01-01

    Glycosylation is an abundant co- and post-translational protein modification of importance to protein processing and activity. Although not template-defined, glycosylation does reflect the biological state of an organism and is a high-potential biomarker for disease and patient stratification. However, to interpret a complex but informative sample like the total plasma N-glycome, it is important to establish its baseline association with plasma protein levels and systemic processes. Thus far, large-scale studies (n >200) of the total plasma N-glycome have been performed with methods of chromatographic and electrophoretic separation, which, although being informative, are limited in resolving the structural complexity of plasma N-glycans. MS has the opportunity to contribute additional information on, among others, antennarity, sialylation, and the identity of high-mannose type species. Here, we have used matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR)-MS to study the total plasma N-glycome of 2144 healthy middle-aged individuals from the Leiden Longevity Study, to allow association analysis with markers of metabolic health and inflammation. To achieve this, N-glycans were enzymatically released from their protein backbones, labeled at the reducing end with 2-aminobenzoic acid, and following purification analyzed by negative ion mode intermediate pressure MALDI-FTICR-MS. In doing so, we achieved the relative quantification of 61 glycan compositions, ranging from Hex4HexNAc2 to Hex7HexNAc6dHex1Neu5Ac4, as well as that of 39 glycosylation traits derived thereof. Next to confirming known associations of glycosylation with age and sex by MALDI-FTICR-MS, we report novel associations with C-reactive protein (CRP), interleukin 6 (IL-6), body mass index (BMI), leptin, adiponectin, HDL cholesterol, triglycerides (TG), insulin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and smoking. Overall, the

  12. Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health.

    Science.gov (United States)

    Reiding, Karli R; Ruhaak, L Renee; Uh, Hae-Won; El Bouhaddani, Said; van den Akker, Erik B; Plomp, Rosina; McDonnell, Liam A; Houwing-Duistermaat, Jeanine J; Slagboom, P Eline; Beekman, Marian; Wuhrer, Manfred

    2017-02-01

    Glycosylation is an abundant co- and post-translational protein modification of importance to protein processing and activity. Although not template-defined, glycosylation does reflect the biological state of an organism and is a high-potential biomarker for disease and patient stratification. However, to interpret a complex but informative sample like the total plasma N-glycome, it is important to establish its baseline association with plasma protein levels and systemic processes. Thus far, large-scale studies (n >200) of the total plasma N-glycome have been performed with methods of chromatographic and electrophoretic separation, which, although being informative, are limited in resolving the structural complexity of plasma N-glycans. MS has the opportunity to contribute additional information on, among others, antennarity, sialylation, and the identity of high-mannose type species.Here, we have used matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR)-MS to study the total plasma N-glycome of 2144 healthy middle-aged individuals from the Leiden Longevity Study, to allow association analysis with markers of metabolic health and inflammation. To achieve this, N-glycans were enzymatically released from their protein backbones, labeled at the reducing end with 2-aminobenzoic acid, and following purification analyzed by negative ion mode intermediate pressure MALDI-FTICR-MS. In doing so, we achieved the relative quantification of 61 glycan compositions, ranging from Hex 4 HexNAc 2 to Hex 7 HexNAc 6 dHex 1 Neu5Ac 4 , as well as that of 39 glycosylation traits derived thereof. Next to confirming known associations of glycosylation with age and sex by MALDI-FTICR-MS, we report novel associations with C-reactive protein (CRP), interleukin 6 (IL-6), body mass index (BMI), leptin, adiponectin, HDL cholesterol, triglycerides (TG), insulin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and smoking. Overall

  13. Low protein and high-energy diet: a possible natural cause of fatty liver hemorrhagic syndrome in caged White Leghorn laying hens.

    Science.gov (United States)

    Rozenboim, I; Mahato, J; Cohen, N A; Tirosh, O

    2016-03-01

    Fatty liver hemorrhagic syndrome (FLHS) is a metabolic condition of chicken and other birds caused by diverse nutritional, hormonal, environmental, and metabolic factors. Here we studied the effect of different diet composition on the induction of FLHS in single comb White Leghorn (WL) Hy-line laying hens. Seventy six (76) young WL (26 wks old) laying hens and 69 old hens (84 wks old) of the same breed were each divided into 4 treatment groups and provided 4 different diet treatments. The diet treatments included: control (C), 17.5% CP, 3.5% fat (F); normal protein, high fat (HF), 17.5% CP, 7% F; low protein, normal fat (LP), 13% CP, 3.5% F; and low protein, high fat (LPHF), 13% CP, 6.5% F. The diets containing high fat also had a higher ME of 3,000 kcal/kg of feed while the other 2 diets with normal fat had a regular lower amount of ME (2750 kcal/kg). Hen-day egg production (HDEP), ADFI, BW, egg weight, plasma enzymes indicating liver damage (alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT]), liver and abdominal fat weight, liver color score (LCS), liver hemorrhagic score (LHS), liver fat content (LFC), liver histological examination, lipid peroxidation product in the liver, and genes indicating liver inflammation were evaluated. HDEP, ADFI, BW, and egg weight were significantly decreased in the LPHF diet group, while egg weight was also decreased in the LP diet group. In the young hens (LPHF group), ALP was found significantly higher at 30 d of diet treatment and was numerically higher throughout the experiment, while AST was significantly higher at 105 d of treatment. LCS, LHS, and LFC were significantly higher in young hens on the LPHF diet treatment. A liver histological examination shows more lipid vacuolization in the LPHF treatment diet. HF or LP alone had no significant effect on LFC, LHS, or LCS. We suggest that LP in the diet with higher ME from fat can be a possible natural cause for predisposing laying hens

  14. 78 FR 44052 - Airworthiness Directives; Sikorsky Aircraft Corporation (Sikorsky) Model Helicopters

    Science.gov (United States)

    2013-07-23

    ..., which proposed establishing new fatigue life limits for certain GE engine gas generator turbine (GGT... limits need to be based on low cycle fatigue (LCF) events instead of hours time-in- service. This action would retain the previously proposed requirements but correct the life limit formula for a certain GGT...

  15. Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells

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    Wu Kong-Yan

    2010-06-01

    Full Text Available Abstract Background During cerebellar development, Purkinje cells (PCs form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs. Results We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML, the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor (BDNF promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT. Conclusion Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo.

  16. DQA2

    Indian Academy of Sciences (India)

    mukesh

    , GGT, CCC, TCT, GGC, CAG, TAC, ACC, CAG, GAA, TTT, GAT, GGA, GAC, GAG, ATG, TTT, TAT, GTG, GAC, CTG, GGG, AAG, AAG, GAG, ACT, GTC, TGG, AGG, CTG, CCT, ATG, TTT, AGC, CAG, TTT, GCA, GGT, TTT, GAC, CCA, CAG, GCT ...

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

    Science.gov (United States)

    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