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| 1 | Therapeutic potential of targeting the renin angiotensin system in portal hypertension显示文摘Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered 'alternate axis' of the RAS. | Chandana B Herath Josephine A Grace Peter W Angus | 2013 | World Journal of Gastrointestinal Pathophysiology2013，4，1： | 9 |
| 2 | 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 |
| 3 | Clearance of hepatitis B eantigen in patients with chronic hepatitis B and genotypes A,B,C,D and F显示文摘 | Stephen E L Josephine P S Lisa R B | 2007 | Gastroenterology2007，133，5： | 1 |
| 4 | Genmic polymorphism of human papillomavirus type52 predisposes toward persistent infection In sexually active women显示文摘 | Josephine A atherine H K Cecile T B | 2004 | Infec Dis2004，190，1： | 1 |
| 5 | Autism spectrum disorders in infancy and toddlerhood:A review of the evidence on early signs,early identification tools,and early diagnosis显示文摘 | Josephine B Cheryl D | | 0，，05： | 1 |
| 6 | Silicene and transition metal based materials: prediction of a two-dimensionalpiezomagnet显示文摘 | Nelson Y Dzade Kingsley O Obodo Sampson K Adjokatse Akosa C Ashu Emmanuel Amankwah Clement D Atiso Abdulhakeem A Bello Emmanuel Igumbor Stany B Nzabarinda Joshua T Obodo Anthony O Ogbuu Olu Emmanuel Femi Josephine O Udeigwe Umesh V Waghmare | 2010 | Journal of Physics: Condensed Matter2010，，： | 1 |
| 7 | Pro-environmental products: Marketinginfluence on consumer purchase decision显示文摘 | JOSEPHINE P B RITSUKO 0 | 2008 | The Journal of ConsumerMarketing2008，25，5： | 1 |
| 8 | An investigation of the factors associated with an increased risk of psychological morbidity in burn injured patients显示文摘 | Nicholas T Eric B | 1998 | Burns1998，24，： | 1 |
| 9 | Simultaneous determination of nine intense sweeteners in foodstuffs by high performance liquid chromatography and evaporative light scattering detection - Development and single - laboratory validation 显示文摘 | Andrzej W Josephine M Manuela B | 2007 | J Chromatogr A2007，1157，： | 1 |
| 10 | Polychlorinated biphenyls and their biodegradation显示文摘 | Josephine B Donna M T Joseph A Susan G | 2005 | Process Biochemistry2005，40，： | 1 |
| 11 | Polychlorinated biphenyls and their biodegradation显示文摘 | Josephine B Donna M T Joseph A | 2005 | Process Biochem2005，40，： | 1 |
| 12 | Measuring the benefits of health promotion programmes: Application of the contingent valuation method显示文摘 | JOSEPHINE B STEPHEN J | 2008 | Health Policy2008，87，23： | 1 |
| 13 | Polychlorinated biphenyls and their biodegradation显示文摘 | Josephine B Donna MT Joseph A | 2005 | Process Biochemistry2005，40，： | 1 |
| 14 | Phylogeny of the sox family of developmental t ranseription factors based on sequence and structural indicators显示文摘 | Josephine B Goslik S Peter K | 2000 | Developmental Biology2000，227，2： | 1 |
| 15 | An Investigation of the Factors Associated with All Increased Risk of Psychological Morbidity in Bum Injured Patients显示文摘 | Josephine E T Nicholas T Erio B | 1998 | Bums1998，，24： | 1 |
| 16 | Simultaneous determination of nine intense sweeteners in foodstuffs by high performance liquid chromatography and evaporative light scattering detection - Development and single - laboratory validation 显示文摘 | ANDRZEJ W JOSEPHINE M MANUELA B | 2007 | J Chromatogr A2007，1157，： | 1 |
| 17 | 18F-FDGPET versus CT for evaluating the spleen during Intial stagingof lymphoma 显示文摘 | Josephine NR John C* Maria L Tomas B | 2003 | J Nucl Med2003，44，7： | 1 |
| 18 | Direct continuous hydrothermal synthesis of high surface area nanosized titania显示文摘 | Zhice Zhang Sonal Brown Josephine B M | 2009 | Journal of Alloys and Compounds2009，，476： | 1 |
| 19 | Female entrepreneursout of the frying pan,into the Fire显示文摘 | JOSEPHINE B THERESE M ANNIE S | 2007 | The Irish Journal of Management2007，，5： | 1 |
| 20 | Sequence de-termination and molecular analysis of two strains of bovine parainfluenza virus type3 that are attenuated for primates显示文摘 | Jane E B Josephine M M Mario H S | 2000 | Virus Genes2000，20，2： | 1 |
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