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| 1 | Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease显示文摘AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. | Christopher Leung Chandana B Herath Zhiyuan Jia Sof Andrikopoulos Bronwyn E Brown Michael J Davies Leni R Rivera John B Furness Josephine M Forbes Peter W Angus | 2016 | World Journal of Gastroenterology2016，22，35： | 7 |
| 2 | Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients显示文摘AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population. | Ana Teresa P Carvalho Barbara C Esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza | 2014 | World Journal of Gastroenterology2014，20，12： | 3 |
| 3 | Bose-Einstein condensation in a gas of sodium atoms显示文摘 | DAVIES K B MEWES M O ANDERSON M R | 1995 | Phys Rev Lett1995，75，22： | 2 |
| 4 | X-ray interactions: photabsorption, scattering, transmission, and reflection at E-50-30000 eV, Z=1-92显示文摘 | HENKE B L GULLIKSON E M DAVIS J C | 1993 | Atomic Data and Nuclear Tables1993，54，： | 2 |
| 5 | User acceptance of information technology: toward a unified view 显示文摘 | VENKATESH V MORRIS M G DAVIS G B | 2003 | MIS Quarterly2003，27，3： | 1 |
| 6 | Impact dynamics in milling of thin-walled structures 显示文摘 | Davies M A Balachandran B | 2000 | Nonlinear Dynamic2000，22，4： | 1 |
| 7 | Rainbow trout has two genes for growth hormone显示文摘 | Agellon L B Davies S L Lin C M | 1988 | Mol Rep Develop1988，1，： | 1 |
| 8 | Identification of RAPD markers linked to phytophthora fragariae resistance gene (Rpf1) in the cultivated strawberry显示文摘 | Haymes K M Henken B Davis T M | 1997 | Theor Appl Genet1997，94，： | 1 |
| 9 | Outbreaks of forest pathogens in Quaternary history显示文摘 | DAVIS M B | 1981 | Proc 4th Int palynolog Conf1981，3，： | 1 |
| 10 | Deciphering the biology of My cobacterium tuberculosis from the complete genome sequence 显示文摘 | Cole S T Brosch R Parkhill J Gamier T Churcher C Harris D Gordon S V Eiglmeier K Gas S Barry C E Tekaia F Badcock K Basham D Brown D Chillingworth T Cormor R Davies R Devlin K FeltweU T Gentles S Hamlin N Holroyd S Hornsby T Jagels K Kroghs A McLean J Moule S Murphy L Oliver K Osborne J Quail M A Rafandream M A Rogers J Rutter S Seeger K Skelton J Squaraes R Squares S Sulston J E Taylo K Whitehead S Barrell B G | 1998 | Nature1998，393，： | 1 |
| 11 | X-ray interactions: photoabsorption scattering, transmission and reflection at E=50-30000 eV, Z=1-92显示文摘 | HENKE B L GULLIKSON E M DAVIS J C | 1993 | Atomic Data and Nuclear Data Tables1993，54，： | 1 |
| 12 | Excitatory GA BA responses in embryonic and neonatal cortical slices demon strated by grarnicidin perforated- patch recordings and calei um imaging显示文摘 | Owens D F Boyce L H Davis M B | 1996 | J Neurosci1996，16，20： | 1 |
| 13 | Calcium anidotrihydroborate:a hydrogen storage material显示文摘 | Diyabalanage H V K Shrestha R P Semelsberger TA Scott B L Bowden M E Davis B L Burrell A K | | 0，，47： | 1 |
| 14 | Fischer-Tropsch reactors显示文摘 | Steynberg A Dry M Davis B | 2004 | Studies in Surface Science and Catalysis2004，152，： | 1 |
| 15 | Chromium oligopeptide activates insulin receptor tyrosin kinase activity 显示文摘 | Davis C M Vincent J B | 1997 | Biochem1997，36，15： | 1 |
| 16 | The expression of calbindin in chicks that are divergently selected for low or high incidence of tibial dyschondroplasia显示文摘 | SHIRLEY R B DAVIS A J COMPTON M M | 2003 | Poultry Science2003，82，12： | 1 |
| 17 | Dynamic measurement of the viscoelastic properties of skin 显示文摘 | Pereira J M Mansour J M Davis B R | 1991 | Journal of Biomechanics1991，24，： | 1 |
| 18 | Fluorescent methods for measuring and imaging cytosolic free Ca^2+ in neutrophils显示文摘 | Hallett M B Davies E V Pettit E J | 1996 | Methods1996，9，3： | 1 |
| 19 | Genetics of Parkinsonism:A review显示文摘 | VAUGHAN J R DAVIS M B WOOD N W | 2001 | Annals of Human Genetics2001，65，2： | 1 |
| 20 | The Stability of Low Radial Immersion Milling 显示文摘 | DAVIES M A DUTTERER B PRATT J R | 2000 | Annals of the CIRP2000，49，1： | 1 |
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