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| 1 | Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases显示文摘Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy. | Ulrike Billmeier Walburga Dieterich Markus F Neurath Raja Atreya | 2016 | World Journal of Gastroenterology2016，22，42： | 19 |
| 2 | First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy显示文摘We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. | Raja Atreya Ulrike Billmeier Timo Rath Jonas Mudter Michael Vieth Helmut Neumann Markus F Neurath | 2015 | World Journal of Gastroenterology2015，21，45： | 5 |
| 3 | Comparison of Hemospray~? and Endoclot? for the treatment of gastrointestinal bleeding显示文摘BACKGROUND Gastrointestinal(GI) bleeding is a common indication for endoscopy. For refractory cases, hemostatic powders(HP) represent 'touch-free' agents.AIM To analyze short term(ST-within 72 h-) and long-term(LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray(HS) and Endoclot(EC).METHODS HP was applied in 154 consecutive patients(mean age 67 years) with GI bleeding.Patients were followed up for 1 mo(mean follow-up: 3.2 mo).RESULTS Majority of applications were in upper GI tract(89%) with following bleeding sources: peptic ulcer disease(35%), esophageal varices(7%), tumor bleeding(11.7%), reflux esophagitis(8.7%), diffuse bleeding and erosions(15.3%). Overall ST success was achieved in 125 patients(81%) and LT success in 81 patients(67%). Re-bleeding occurred in 27% of all patients. In 72 patients(47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding(P = 0.04)CONCLUSION Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding. | Francesco Vitali Andreas Naegel Raja Atreya Steffen Zopf Clemens Neufert Juergen Siebler Markus F Neurath Timo Rath | 2019 | World Journal of Gastroenterology2019，25，13： | 2 |
| 4 | Pneumococcal antimicro-bial resistance:therapeutic strategy and management in community-acquired pneumonia显示文摘 | Aspa J Rajas O de Castro F R | 2008 | Expert Opin Pharmacother2008，9，2： | 1 |
| 5 | The Impact of Personality on Psychological Contracts 显示文摘 | Raja U Johns G Ntalianis F | 2004 | Academy of Management Journal2004，，3： | 1 |
| 6 | Drug-resistant pneumococcal pneumonia:clinical relevance and related factors显示文摘 | Aspa J Rajas O Rodriguez de Castro F | 2004 | Clin Infec DiS2004，38，： | 1 |
| 7 | Relative contribution of core and skin temperatures to thermal comfort in humans 显示文摘 | Bulcao C F Frank S M Raja S N Tran K M Goldstein D S | 2000 | Journal of Thermal Biology2000，25，12： | 1 |
| 8 | Climatic variations in comfortable temperatures: the Pakistan projects显示文摘 | NICOL J F RAJA I A ALLAUDIN A | 1999 | Energy and Buildings1999，30，3： | 1 |
| 9 | The Impact of Personality on Psychological Contracts 显示文摘 | RAJA U JOHNS G NTALIANIS F | 2004 | Academy of Management Journal2004，47，3： | 1 |
| 10 | A Practical Knowledge Transfer System: A Case Study 显示文摘 | Fernandes K F Raja V | 2002 | Work Study2002，51，3： | 1 |
| 11 | Recent advances in separation of roughness,waviness and form显示文摘 | RAJA J MURALIKRISHNAN B SHENGYU F | 2002 | Precision Engineering2002，26，2： | 1 |
| 12 | Engineering surface analysis with different wavelet bases显示文摘 | SHENGYU F MURALIKRISHNAN B RAJA J | 2003 | Journal of Manufacturing Science and Engineering2003，125，： | 1 |
| 13 | Lessons from new mouse models of glycogen storage disease type la in relation to the time course and organ specificity of the disease 显示文摘 | Rajas F Clar J Gautier-Stein A | 2015 | J Inherit Metab Dis2015，38，3： | 1 |
| 14 | Recognition of discharge sources using UHF PD signatures显示文摘 | RAJA K DEVAUX F | 2002 | IEEE Electrical Insulation Magazine2002，18，5： | 1 |
| 15 | Immunocytochemical localization of glucose 6-phosphatase and cytosolic phos-phoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation显示文摘 | Rajas F Jourdan-Pineau H Stefanutti A | | 0，，： | 1 |
| 16 | The impact of personality on psychological contracts 显示文摘 | Raja U Johns G Ntalianis F | 2004 | Academy of Management Journal2004，47，3： | 1 |
| 17 | Rat small intestine is an insu-lin-sensitive gluconeogenic organ显示文摘 | Croset M Rajas F Zitoun C | | 0，，： | 1 |
| 18 | Glycogen storage disease type 1 and diabetes: learning by comparing and contrasting the two disorders显示文摘 | Rajas F Labrune P Mithieux G | 2013 | Diabetes Metab2013，39，5： | 1 |
| 19 | Contribution of intes-tine and kidney to glucose fluxes in different nutritional states in rat显示文摘 | Mithieux G Gautier-Stein A Rajas F | | 0，，： | 1 |
| 20 | Thermal Comfort:Use of Controls in Naturally Ventilated Buildings显示文摘 | RAJA I A NICOL J F McCartney K J | 2001 | Energy and Buildings2001，33，3： | 1 |
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