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Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

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World Journal of Gastroenterology 2005年第44期11卷 7001-7006页

作者： Wolfgang Kruis Axel Dignass Elisabeth Steinhagen-Thiessen Julia Morgenstern Joachim M(o|¨)ssner Stephan Schreiber Maurizio Vecchi Alberto Malesci Max reinshagen robert L(o|¨)fberg Evangelisches Krankenhaus Kalk medizinische klinik für Hepatologie und Gastroenterologie medizinische klinik und poliklinik Ⅱ medizinische klinik Dep of Int Medicine IrCCS Ospedale Policlinico Istituto Clinico Humanitas innere medizin Karolinska Institute at the IBD unit

AIM： To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS： An open label multicenter study was carried out in 39 patients with active ulcerative colitis （CAI 6-8） despite continuous use of steroids （a minimum total dose of 400 mg prednisone within the last 4 wk）. Patients received a total of five aphereses using a granulocyte adsorptive technique （Adacolumn, Otsuka Pharmaceutical Europe, UK）. Assessments at wk 6 and during follow-up until 4 mo comprised clinical （CAI） and endoscopic （EI） activity index, histology, quality of life （IBDQ）, and laboratory tests. rESULTS： Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 （37.1%） patients achieved clinical remission and 10/35 （28.6%） patients had endoscopic remission （CAI〈4, EI〈4）. Quality of life （IBDQ） increased significantly （24 points, P〈0.01） at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION： In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

关键词： Steroid refractory colitis Ulcerative colitis Granulocyte Apheresis

Translocator protein and neurodegeneration: insights from Alzheimer’s disease

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Neural regeneration research 2025年第4期20卷 1090-1091页

作者： Arpit Kumar Pradhan rainer rupprecht Gerhard rammes klinik für Anaesthesiologie und Intensivmedizin der Technischen Universität München Klinikum rechts der IsarMunichGermany Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität MünchenMartinsriedGermany Department of Psychiatry and Psychotherapy University RegensburgRegensburgGermany

The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce *** main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.

关键词： cholesterol organs

Treatment of eosinophlic esophagitis with swallowed topical corticosteroids

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World Journal of Gastroenterology 2020年第36期26卷 5395-5407页

作者： Simon Nennstiel Christoph Schlag klinikum rechts der Isar der Technischen Universität München Klinik und Poliklinik für Innere Medizin IIMunich 81675Germany

Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the *** proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current *** review describes the background and practical management of STCs in *** far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June *** it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance ***,current studies on STC maintenance therapy add some movement into the game.

关键词： Eosinophilic esophagitis Swallowed topical corticosteroids Esophagustargeted formulations of topical steroids fluticasone Budesonide Budesonide orodispersible tablet Budesonide oral suspension

reduced expression of Ca^(2+)-regulating proteins in the upper gastrointestinal tract of patients with achalasia

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World Journal of Gastroenterology 2006年第37期12卷 6002-6007页

作者： Harald fischer Judith fischer Peter Boknik Ulrich Gergs Wilhelm Schmitz Wolfram Domschke Jan W Konturek Joachim Neumann medizinische klinik und poliklinik B Universittsklinikum Mnster 48129 Mnster Germany Institut fr Pharmakologie und Toxikologie Universittsklinikum Mnster 48149 Mnster Germany Institut fr Pharmakologie und Toxikologie Martin-Luther-Universitt Halle-Wittenberg 06112 Halle (Saale) Germany klinik fr innere medizin/Gastroenterologie Elbe Klinikum Stade 21682 Stade Germany

AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ ATPase (SErCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CrT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. furthermore, expression profi les of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed. rESULTS: SErCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SErCA 2b was expressed predominantly in the esophagus. The highest CrT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CrT expression in lower esophageal sphincter and distal esophageal body were signif icantly reduced in patients with achalasia (P f lesser importance for regulation of SErCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CrT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.

关键词： Esophageal and gastric motility Esophagus Calsequestrin Calreticulin

Uber EKG-Kennzeichungen der atrioventrikul ren akzessorischen Leitungsbahnen von rechtsmittelsepta und Linksmittelsepta

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2001年第1期21卷 26-29页

作者： WANG Lin Ouyang f *** klinikum Hamburg Deutschland Cappato r Hebe J Volkmer M Antz M Ernst S Kuck K H 王琳 Abteilung fur innere medizin Tongji Klinik Tongji Mediszinisches Institut Huazhong Universitat fur Wissenschaft und Technik *** klinikum Hamburg Deutschland

In der Studie wurden 20 Patienten mit AV-reentry Tachykardie unter Einbezug einer mittelseptalen gelegenen atrioventricul ren akzessorischen Leitungsbahn(MS) eingeschlossen, die seit 4 Jahren in unserem Elektrophysiologischen Untersuchungslabor mittels Katheters erfolgreich abladiert wurden. Die 20 Patienten hatten 26 akzessorische Leitungsbahnen. Daunter waren 21 MS (rechtsmittelseptal (rMS) zu linksmittelseptal(LMS)=17:4). 18 akzessorische Leitungsbahnen waren offen. Die Lokalisation der akzessorischen Leitungsbahnen wurde aufgrund der Stelle erfolgreich abladiert bestimmt. Die Ergebnisse zeigten, da die rMS und LMS den gleichen Charakter in den meisten Ableitungen des EKGs hatten, und jedoch der wenige Unterschied bei diesen beiden akzessorischen Lritungsbahnen besteht. Wenn die positive Polaritat der Delta Welle in der Ableitung V 1 bei der Patienten mit MS auftritt, mu sich berlegen, ob die M glichkeit der Lokalisation der akzessorischen Leitungsbahn im Linksmittelseptum besteht.

关键词： Katheterablation rechtsmittelseptale gelegene akzessorische Leitungsbahn linksmittelseptale gelegene akzessorische Leitungsbahn

Die Transmurale ErP-Dispersion von Epi-,Mid-und Endomyokard im gesunden und hypertrophierten Hundemyokard

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2001年第2期21卷 89-92页

作者：吕家高陆再英 Abteilung für Kardiologie Tongji Klinik Tongji Medizinisches Institut Huazhong Universität für Wissenschaft und Technik Wuhan Abteilung für kardiologie Innere Medizin III Universität Heidelberg Deutschland

Viele Studien haben das Vorliegen von M Zellen im Midmyokard des Hundes in vitro beobachtet und weiterhin gefunden, da das Vorliegen von M Zellen zur Differenz der repolarisation und zur Dispersion der refraktarzeit zwischen Midmyokard und Epi und Endomyokard fuhren *** Dispersion hat enge Beziehungen mit der Entstehung der Arrhythmie. Aber die Beobachtungen in vitro waren nicht konkordant mit den Ergebnissen in vivo. Mittels direkten Messungen der ErP in drei Myokardschichten wurde erstmals im gesunden Hundemyokard und im hypertrophierten Hundemyokard in vivo untersucht. Die Untersuchung hat gezeigt, da die ErP von Endomyokard, Epimyokard und Midmyokard im gesunden Hundeherzen homogen sind. Die relevante transmurale refraktargradient, die die Induktion einer kreisenden Erregung begunstigt, besteht unter physiologischen Bedingungen nicht. Im Gegensatz dazu konnte eine deutliche Verlangerung der ErP in allen Myokardschichten von hypertrophierten Hundeherzen nachgewiesen werden.. Weiterhin wurde gezeigt, da eine transmurale ErP Dispersion zwischen verschiedenen Myokardschichten im hypertrophierten Hundemyokard besteht. Es ist zu postulieren, da diese transmurale ErP Dispersion als Substrat fur die Arrhythmie angesehen werden kann,weil diese Dispersion die lokalen kreisende Erregung zwischen Epikard und Midkard, oder zwischen Midkard und Endokard begunstigen kann. Nach den Ergebnissen lat sich postulieren, da eine transmurale ErP Dispersion durch eine plotzliche Zykluslangeveranderung, namlich durch eine Kurz Lang und eine Lang Kurz Sequenz verstarkt werden kann.

关键词： normale Myokard hypertrophierte Myokard transmurale ErP Dispersion

Treatment of gastrointestinal neuroendocrine tumors with inhibitors of growth factor receptors and their signaling pathways: recent advances and future perspectives

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World Journal of Gastroenterology 2008年第16期14卷 2461-2473页

作者： Michael Hpfner Detlef Schuppan Hans Scherübl Institute of Physiology Charité-Universitts-medizin Berlin Campus Benjamin Franklin Beth Israel Deaconess Medical Center and Harvard Medical School klinik für innere medizin Gastroenterologie und Gastrointestinale Onkologie Klinikum am Urban Vivantes Netzwerk für Gesundheit

The limited efficacy of conventional cytotoxic treatment regimes for advanced gastrointestinal neuroendocrine cancers emphasizes the need for novel and more effective medical treatment options. recent findings on the specific biological features of this family of neoplasms has led to the development of new targeted therapies, which take into account the high vascularization and abundant expression of specific growth factors and cognate tyrosine kinase receptors. This review will briefly summarize the status and future perspectives of antiangiogenic, mTOr- or growth factor receptor-based pharmacological approaches for the innovative treatment of gastrointestinal neuroendocrine tumors. In view of the multitude of novel targeted approaches, the rationale for innovative combination therapies, i.e. combining growth factor (receptor)-targeting agents with chemo- or biotherapeutics or with other novel anticancer drugs such as HDAC or proteasome inhibitors will be taken into account.

关键词： Growth factor receptor Neuroendocrinegastrointestinal tumor Small molecule inhibitor lonoclonal antibody Multi kinase inhibition

Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

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World Journal of Gastroenterology 2012年第39期18卷 5542-5550页

作者： ramsi Siaj Vanessa Sauer Sandra Stppeler Hans-Ullrich Spiegel Gabriele Khler Andree Zibert Hartmut HJ Schmidt klinik und poliklinik für Transplantationsmedizin Universittsklinikum MünsterD-48149 MünsterGermany Abteilung Chirurgische forschung Klinik und Poliklinik für Allgemein-und ViszeralchirurgieUniversittsklinikum MünsterD-48149 MünsterGermany Gerhard-Domagk-Institut für Pathologie Universittsklinikum MünsterD-48149 MünsterGermany

AIM： To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS： The Long-Evans cinnamon （LEC） rat mod- el of Wilson＇s disease （WD） was used to study the im- pact of high dietary copper （hCu） on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults （month 5） for three months. Animals that received reduced di- etary copper （rCu） throughout their lifetime served as a control. Hepatitis-associated serum markers （alanine aminotransferase, aspartate transaminase, bilirubin） were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis （Vegfa）, fat metabolism （Srebf1）, ex- tracellular matrix （Timp1）, oxidative stress （Hmox1）, and the cell cycle （Cdknla） were analyzed by real-time polymerase chain reaction. rESULTS： regardless of the time point when hCu was started, LEC rats （35/36） developed fulminant hepati- tis and died. Animals receiving rCu （36/36） remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals （477 ± 75 μg/g）. With regard to start of hCu, onset of fulminant hepatitis was significantly （P 〈 0.001） earlier in adults （35±9 d） that showed pre-accumulation of liver copper as com- pared to the pup group （77±15 d）. Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION： rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical threshold of liver copper which is imp

关键词： Wilson's disease fulminant hepatitis Acuteliver failure Dietary copper Long-Evans cinnamon rat A TP7B

Mandatory criteria for the application of variability-based parameters of fluid responsiveness: a prospective study in different groups of ICU patients

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2018年第7期19卷 515-524页

作者： Wolfgang HUBEr Uli MAYr ANDreas UMGELTEr Michael frANZEN Wolfgang rEINDL rolAND M.SCHMID florian ECKEL Ⅱ. medizinische klinik und poliklinik Klinikum rechts der Isar der Technischen Universitat Munchen Ismaninger Straβe 22 D-81675 Miinchen Germany Universitatsklinik fur innere medizin I Salzburger Landeskliniken Universitatsklinikum Salzburg Mullner Hauptstraβe 48A-5020 Salzburg Austria Ⅱ. medizinische klinik Universitatsklinikum Mannheim Theodor-Kutzer-Ufer 1-3 D-68167 Mannheim Germany klinik fur innere medizin RoMed Klinik Bad Aibling Harthauser Straβe 16 D-83043 Bad Aibling Germany

Background and objective： Stroke volume variation（SVV） has high sensitivity and specificity in predicting fluid responsiveness. However, sinus rhythm（Sr） and controlled mechanical ventilation（CV） are mandatory for their application. Several studies suggest a limited applicability of SVV in intensive care unit（ICU） patients. We hypothesized that the applicability of SVV might be different over time and within certain subgroups of ICU patients. Therefore, we analysed the prevalence of Sr and CV in ICU patients during the first 24 h of Pi CCO-monitoring（primary endpoint） and during the total ICU stay. We also investigated the applicability of SVV in the subgroups of patients with sepsis, cirrhosis, and acute pancreatitis. Methods： The prevalence of Sr and CV was documented immediately before 1241 thermodilution measurements in 88 patients. results： In all measurements, SVV was applicable in about 24%. However, the applicability of SVV was time-dependent： the prevalence of both Sr and CV was higher during the first 24 h compared to measurements thereafter（36.1% vs. 21.9%; P0.001）. Within different subgroups, the applicability during the first 24 h of monitoring ranged between 0% in acute pancreatitis, 25.5% in liver failure, and 48.9% in patients without pancreatitis, liver failure, pneumonia or sepsis. Conclusions： The applicability of SVV in a predominantly medical ICU is only about 25%–35%. The prevalence of both mandatory criteria decreases over time during the ICU stay. furthermore, the applicability is particularly low in patients with acute pancreatitis and liver failure.

关键词： Hemodynamic monitoring Preload fluid responsiveness Stroke volume variation Pulse pressure variation