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Im.act of hyperglycem.a on autoim.une pancreatitis and regulatory T-cells

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World Journal of Gastroenterology 2018年第28期24卷 3120-3129页

作者： Franz-Tassilo m.ller-Graff Brit Fitzner Robert Jaster Brigitte vollmar Dietm.r Zechner Institute for Experim.ntal Surgery Rostock University Medical Center Division of Gastroenterology Department of Medicine Ⅱ Rostock University Medical Center

AIm.To evaluate the influence of hyperglycem.a on the progression of autoim.une *** We induced hyperglycem.a by repetitive intraperitoneal(ip) injection of 50 m./kg streptozotocin in m.L/m. J m.ce, which develop autoim.une pancreatitis due to a genetic predisposition. We com.ared the extent of inflam.ation(histological score, CD3^+ lym.hocytes, CD8^+ T-cells, CD4^+ T-cells, Foxp3^+ T-helper cells) in the pancreas of hyperglycem.c and norm.glycem.c m.ce. We also analyzed the num.er of leukocytes, lym.hocytes, granulocytes and m.nocytes in the blood. In addition, we determ.ned the percentage of CD3^+ lym.hocytes, CD8^+ T-cells, CD4^+ T-cells, Foxp3^+ T-helper cells, Foxp3^+ CD25^+ T-helper and Foxp3^+T-helper cells in the spleen by flow *** Treatm.nt with streptozotocin caused a strong induction of hyperglycem.a and a reduction in body weight(P m.a did not, however, lead to an aggravation, but rather to a slight attenuation of autoim.une pancreatitis. In the pancreas, both the histological score of the pancreas as well as the num.er of CD3+ lym.hocytes(P m.a. No m.jor changes in the percentage of CD8^+ T-cells, CD4^+ T-cells, Foxp3^+ T-helper cells were observed between hyperglycem.c and norm.glycem.c m.ce. Hyperglycem.a increased the num.ers of leukocytes(P m.hocytes(P = 0.016), granulocytes and m.nocytes(P = 0.001) in the blood. Hyperglycem.a also m.derately reduced the percentage of CD3^+ lym.hocytes(P = 0.057), significantly increased the percentage of Foxp3^+ T-helper cells(P = 0.018) and Foxp3^+ CD25^+ T-helper cells(P = 0.021) and reduced the percentage of Foxp3^+T-helper cells(P = 0.034) in the spleen. CONCLUSION Hyperglycem.a does not aggravate but m.derately attenuates autoim.une pancreatitis, possibly by increasing the percentage of regulatory T-cells in the spleen.

关键词： Autoim.une disease Diabetes Treg FoxP3 Autoim.une pancreatitis m.L/m.J m.ce

Hepatocyte cytoskeleton during ischem.a and reperfusion -influence of ANP-m.diated p38 m.PK activation

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World Journal of Gastroenterology 2005年第47期11卷 7418-7429页

作者： m.lanie Keller Alexander L Gerbes Stefanie Kulhanek-Heinze Tobias Gerwig Uwe Grützner Nico van Rooijen angelika m.vollmar Alexandra K Kiem.r Departm.nt of Pharm.cy Centre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Departm.nt of m.dicine Ⅱ Klinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany angelika m.vollmar Alexandra K KiemerDepartment of PharmacyCentre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Departm.nt of Pharm.cy Centre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Department of Medicine ⅡKlinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Institute for Surgical Research Klinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Vrije Universiteit VUMCDepartment of Molecular Cell BiologyFaculty of Medicine1081 BT AmsterdamThe Netherlands

AIm. To determ.ne functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischernia and reperfusion. m.THODS： For in vivo experim.nts, anim.ls received ANP （5 μg/kg） intravenously. In a different experim.ntal setting, isolated rat livers were perfused with KH-buffer ＋ANP （200 nm.l/L）＋SB203580 （2 μm.l/L）. Livers were then kept under ischernic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hsp27 were determ.ned by Western blotting, p38 m.PK activity by in vitro phosphorylation assay. F-actin distribution was determ.ned by confocal m.croscopy. RESULTS： We first confirm.d that ANP preconditioning leads to an activation of p38 m.PK and observed alterations of the cytoskeleton in hepatocytes of ANP- preconditioned organs. ANP induced an increase of hepatic F-actin after ischem.a, which could be prevented by the p38 m.PK inhibitor SB203580 but had no effect on bile flow. After ischem.a untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augm.ntation of Hsp27 phosphorylation. This effect is also m.diated via p38 m.PK, since it was abrogated by the p38 m.PK inhibitor SB203580. CONCLUSION： This study reveals that ANP-m.diated p38 m.PK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first tim. shows functional consequences of ANP-induced hepatic p38 m.PK activation.

关键词： Horm.nal preconditioning Atrial natriuretic peptide Hsp 27 Actin Polym.rization

PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation

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World Journal of Gastroenterology 2006年第7期12卷 1049-1055页

作者： Uwe Grutzner m.lanie Keller m.chael Bach Alexandra K Kiem.r Herbert m.issner m.nfred Bilzer Stefan Zahler Alexander L Gerbes angelika m.vollmar Institute for Surgical Research Klinikum GroBhadernUniversity of MunichD-81377 MunichGermany Departm.nt of Pharm.cy University of MunichD-81377 MunichGermany Departm.nt Institute of Pathology University of MunichD-81377 MunichGermany

AIm. To investigate the in vivo effect of atrial natriuretic peptide （ANP） and its signaling pathway during orthotopic rat liver transplantation.m.THODS： Rats were infused with NaCI, ANP （5 μg/ kg）, wortm.nnin （WH, 16μg/kg）, or a com.ination of both for 20 m.n. Livers were stored in UW solution （4℃） for 24 h, transplanted and reperfused. Apoptosis was exam.ned by caspase-3 activity and TUNEL staining. Phosphorylation of Akt and Bad was visualized by Western blotting and phospho-Akt-localization by confocal m.croscopy.RESULTS： ANP-pretreatm.nt decreased caspase-3 activity and TUNELopositive cells after cold ischem.a, indicating antiapoptotic effects of ANP in vivo. The an- tiapoptotic signaling of ANP was m.st likely caused by phosphorylation of Akt and Bad, since pretreatm.nt with PI 3-kinase inhibitor Wm.abrogated the ANP-induced reduction of caspase-3 activity. Interestingly, analysis of liver tissue by confocal m.croscopy showed translocation of phosphorylated Akt to the plasm. m.m.rane of hepa- tocytes evoked by ANP.CONCLUSION： ANP activates the PI-3-kinase pathway in the liver in vivo leading to phosphorylation of Bad an event triggering antiapoptotic signaling cascade in ischem.c liver.

关键词： Bad Apoptosis Horm.nal preconditioning Ischem.a reperfusion injury

高分辨螺旋CT在乳腺的低剂量扫描:理念和可行性思考

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国际医学放射学杂志 2012年第2期 188-188页

作者： W.A.Kalender m.Beister J.m.Boone D.Kolditz S.V.vollmar m.C.C.Weigel 胡芳 Institute of m.dical Physics University Erlangen-NürnbergHenkestr.9191052 ErlangenGermany

目的作为目前乳腺常规的影像学检查方法,X线摄影对解剖结构的重叠显示仍显不足。目前乳腺专用CT可以获得优良的软组织影像,但空间分辨力和剂量等原因使其应用受到限制。就最新的乳腺专用CT技术进行了评估。方法通过反复模拟和测量,开发... 详细信息

目的作为目前乳腺常规的影像学检查方法,X线摄影对解剖结构的重叠显示仍显不足。目前乳腺专用CT可以获得优良的软组织影像,但空间分辨力和剂量等原因使其应用受到限制。就最新的乳腺专用CT技术进行了评估。方法通过反复模拟和测量,开发的新技术为采用直接转换材料

关键词： CT 乳腺影像质量空间分辨率剂量利用率