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Lipid Based Therapy for Ulcerative Colitis—Modulation of Intestinal Mucus Membrane Phospholipids as a Tool to Influence Inflammation
Hannah Schneider,Annika Braun,Joachim Füllekrug,Wolfgang Stremmel,Robert Ehehalt
International Journal of Molecular Sciences , 2010, DOI: 10.3390/ijms11104149
Abstract: Ulcerative colitis (UC) is the result of an inappropriate colonic inflammatory response triggered by environmental and genetic factors. We have recently shown that mucus from UC patients has a decreased phosphatidylcholine (PC) content, while clinical trials revealed that therapeutic addition of PC to the colonic mucus alleviated the inflammatory activity. The mechanisms behind this are still unclear. We hypothesized that PC has at least two possible functions in the intestine: First, it establishes the surface hydrophobicity of the mucus and therefore protects the underlying tissue against intraluminal aggressors; recent experiments on surgical specimens revealed reduced surface tension and hydrophobicity in UC patients. Second, mucus phospholipids might also be integrated into the plasma membranes of enterocytes and thereby influence the signaling state of the mucosa. PC has been shown to inhibit TNF-α induced pro-inflammatory responses including: (1) assembly of plasma membrane actin; (2)?activation of MAP kinases ERK and p38; and (3) activation of NF-κB and synthesis of pro-inflammatory gene products. Other phospholipids like phosphatidylethanolamine or sphingomyelin ?had no effect. PC also inhibited latex bead phagosome actin assembly, killing of M. tuberculosis in macrophages, and sphingosine-1-phosphate induced actin assembly in macrophages. Collectively, these results provide a molecular foundation that shows PC, firstly, as an anti-inflammatory, and secondly, as a surface hydrophobicity increasing compound with promising therapeutic potential in the treatment of inflammatory bowel disease.
Transcript levels of different cytokines and chemokines correlate with clinical and endoscopic activity in ulcerative colitis
Alexandra Zahn, Thomas Giese, Max Karner, Annika Braun, Ulf Hinz, Wolfgang Stremmel, Robert Ehehalt
BMC Gastroenterology , 2009, DOI: 10.1186/1471-230x-9-13
Abstract: Cytokine and chemokine transcripts were quantified using real-time PCR in 49 mucosal biopsies from 27 different patients with UC. Cytokine transcript levels were correlated with CAI and EAI.There was a statistically significant positive correlation between CXCL8 (r = 0.30; p < 0.05), CXCL10 (r = 0.40; p < 0.02), calgranulin B (r = 0.36; p < 0.03), CXCL2 (r = 0.31; p < 0.05) and CAI. Concerning EAI significant positive correlations for CXCL8 (r = 0.37; p < 0.02), CXCL10 (r = 0.33; p < 0.04), calgranulin B (r = 0.31; p < 0.05) and CXCL2 (r = 0.44; p < 0.05) were found. Low clinical and endoscopic activity was accompanied by low cytokine levels whereas high CAI and EAI were associated with high cytokine levels.From our data, we conclude that real-time PCR quantification of CXCL8, CXCL10, calgranulin B and CXCL2 in colonic biopsies is a simple and objective method for grading inflammation of intestinal mucosa in UC. CXCL8, CXCL10, calgranulin B and CXCL2 might be used as biomarkers and thus as an objective tool especially in clinical trials to evaluate anti-inflammatory and immunomodulatory regimens.Inflammatory bowel disease (IBD) like ulcerative colitis (UC) and Crohn's disease (CD) are characterized by a relapsing and remitting clinical course. Disease activity and severity are variable and include both segmental processes with slight impairment of state of health and pancolitis with extensive gastrointestinal and systemic symptoms. Thus, the definition of disease activity in UC is often difficult. The clinical activity index (CAI) is only an indirect assessment tool of bowel inflammation and the endoscopic activity index (EAI) is sometimes unable to reflect the severity of disease to the full extent.Cytokine and chemokine mRNA expression profiles in UC have been characterized in former studies [1-3] and interleukin 8 (CXCL8), interferon γ inducible protein 10 (CXCL10), myeloid-related protein 14 (calgranulin B) and macrophage inflammatory protein 2 α (CXCL2) were id
Separate basolateral and apical phosphatidylcholine secretion routes in intestinally differentiated tumor cells
Daniel Gotthardt, Annika Braun, Anke Tietje, Karl Heinz Weiss, Robert Ehehalt, Wolfgang R Stremmel
World Journal of Gastroenterology , 2009,
Abstract: AIM: To investigate whether the secretion of phosphatidylcholine (PC) in intestinal mucus occurs by apical secretion or via basolateral excretion and to determine its subsequent passage across the tight junctions to the apical mucus.METHODS: We addressed this question using the polarized intestinally differentiated tumor cell line CaCo-2 grown on filters to confluence in Transwell culture chambers. The released PC and sphingomyelin (Sph) from apical and basolateral media were analyzed by mass spectrometry.RESULTS: The secreted PC species were identical in both compartments indicating the same intracellular origin of PC. However, PC secretion into the basolateral compartment was more effective, and the PC:Sph ratio in the basolateral compartment was significantly higher than that in the apical compartment (8.18 ± 1.84 vs 4.31 ± 1.22, P = 0.01). Both pathways were temperature sensitive and were unaltered in the presence of cyclosporine.CONCLUSION: The data demonstrate the PC secretion capacity of CaCo-2 cells and indicate two separated apical and basolateral release mechanisms.
TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells
Irina Treede, Annika Braun, Petia Jeliaskova, Thomas Giese, Joachim Füllekrug, Gareth Griffiths, Wolfgang Stremmel, Robert Ehehalt
BMC Gastroenterology , 2009, DOI: 10.1186/1471-230x-9-53
Abstract: PC species with different fatty acid side chains were applied to differentiated and non-differentiated Caco-2 cells treated with TNF-α to induce a pro-inflammatory response. We analysed TNF-α-induced NF-κB-activation via the transient expression of a NF-κB-luciferase reporter system. Pro-inflammatory gene transcription was detected with the help of a quantitative real time (RT)-PCR analysis. We assessed the binding of TNF-α to its receptor by FACS and analysed lipid rafts by isolating detergent resistant membranes (DRMs).The exogenous addition of all PC species tested significantly inhibited TNF-α-induced pro-inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF-α and MMP-1 were significantly reduced after PC pre-treatment for at least two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB inhibitor SN 50 and was not due to a reduced binding of TNF-α to its receptor or a decreased surface expression of TNF-α receptors. PC was also effective when applied to the apical side of polarised Caco-2 cultures if cells were stimulated from the basolateral side. PC treatment changed the compartmentation of the TNF-α-receptors 1 and 2 to DRMs.PC induces a prolonged inhibition of TNF-α-induced pro-inflammatory signalling. This inhibition may be caused by a shift of the TNF-α receptors at the surface to lipid rafts. Our results may offer a potential molecular explanation for the positive role of PC seen in clinical studies for the treatment of ulcerative colitis.Inflammatory bowel disease (IBD) is the result of a chronic intestinal inflammatory response. While the exact pathogenesis of IBD remains incompletely understood, it is likely that the initiation of the immune response is triggered by luminal factors [1]. The nature of these initiating agents is unclear, but both orally ingested nutrients and microbial agents have been implicated [2]. It is widely believed that an impaired barrier function, and in particular a defect of th
Expression profiles of hydrophobic surfactant proteins in children with diffuse chronic lung disease
Matthias Griese, Silja Schumacher, Mohammed Tredano, Manuela Steinecker, Annika Braun, Susan Guttentag, Michael F Beers, Michel Bahuau
Respiratory Research , 2005, DOI: 10.1186/1465-9921-6-80
Abstract: We analyzed bronchoalveolar lavage fluid by Western blotting for SP-B, SP-C and their proforms in children with pulmonary alveolar proteinosis (PAP, n = 15), children with no SP-B (n = 6), children with chronic respiratory distress of unknown cause (cRD, n = 7), in comparison to children without lung disease (n = 15) or chronic obstructive bronchitis (n = 19).Pro-SP-B of 25–26 kD was commonly abundant in all groups of subjects, suggesting that their presence is not of diagnostic value for processing defects. In contrast, pro-SP-B peptides cleaved off during intracellular processing of SP-B and smaller than 19–21 kD, were exclusively found in PAP and cRD. In 4 of 6 children with no SP-B, mutations of SFTPB or SPTPC genes were found. Pro-SP-C forms were identified at very low frequency. Their presence was clearly, but not exclusively associated with mutations of the SFTPB and SPTPC genes, impeding their usage as candidates for diagnostic screening.Immuno-analysis of the hydrophobic surfactant proteins and their precursor forms in bronchoalveolar lavage is minimally invasive and can give valuable clues for the involvement of processing abnormalities in pediatric pulmonary disorders.Pulmonary surfactant is a highly surface active complex of lipids and specific proteins, including surfactant proteins (SP-) A, B, C and D [1]. The maintenance of the patency of the airspaces at end-expiration is heavily dependent on the phospholipid components and their interaction with SP-B and SP-C [2]. SP-B is encoded by a single gene (SFTPB) [3] and translated in the alveolar type II cells into a preproprotein (~40 kDa). Post-translational processing of pro-SP-B to yield mature SP-B is a multistep entirely intracellular process involving multiple sites and enzymes [4-7]. SP-C is encoded by the SFTPC gene on chromosome 8 [8] and the SP-C proprotein processing [9-11] is integrally linked to the metabolism of SP-B in that infants and mice with genetic SP-B deficiency exhibit incompletely p
Injuries of Three Health Care Districts Employees in Finland  [PDF]
Simo Salminen, Annika Parantainen
Open Journal of Safety Science and Technology (OJSST) , 2012, DOI: 10.4236/ojsst.2012.23014
Abstract: Abstract: Occupational injuries in hospitals have two-fold effects, decreasing both safety employees and the level of patient care. The aim of this study is to examine occupational injuries in Finnish hospitals. Three health care districts reported injuries and violent acts and the number of their employees over a period of three years: 2006-2008. Every eighth hospital worker was involved in an occupational injury each year, which is more than among the general working population. In addition, every twentieth hospital employee had encountered violence or a threat of violence in their work, which corresponds to the risk of violence among working men. There were huge differences in injury and violence rates between health care districts, which were due to different reporting procedures used in districts. Underreporting is another possible explanatory factor especially for minor injuries and verbal aggression.
Island: Alte Literaturtradition und moderne Bibliotheken
Annika Baecker
Libreas : Library Ideas , 2006,
Review: Dominik Schrage (Hrsg.) (2005). Die Flut. Diskursanalysen zum Dresdner Hochwasser im August 2002 Review: Dominik Schrage (Ed.) (2005). Die Flut. Diskursanalysen zum Dresdner Hochwasser im August 2002 [The Flood. Discourse Analyses on the Dresden Flood in August 2002] Rese a: Dominik Schrage (Ed.) (2005). Die Flut. Diskursanalysen zum Dresdner Hochwasser im August 2002 [La inundación. Análisis del Discurso de la inundación de Dresde en Agosto de 2002]
Annika Mattissek
Forum : Qualitative Social Research , 2007,
Abstract: In dem von Dominik SCHRAGE herausgegebenen Band sind die Ergebnisse eines Forschungsseminars am Institut für Soziologie der TU Dresden (Sommersemester 2004 und Wintersemester 2004/05) dokumentiert. Die Beitr ge resultieren aus einer Untersuchung der (print-) medialen Berichterstattung zum Elbhochwasser im Sommer 2002 mit Hilfe diskursanalytischer Verfahren. Themen sind neben einigen grunds tzlichen überlegungen zur Umsetzung FOUCAULTscher Diskurstheorie in empirischen Forschungsarbeiten formale Aspekte des Flutdiskurses, die gegenseitige Beeinflussung von Wahlkampf- und Flutberichterstattung sowie das w hrend des Hochwassers gezeichnete Naturbild. Der Sammelband zeigt auf überzeugende Art und Weise, dass FOUCAULTsche Diskursanalyse für die Analyse aktueller gesellschaftlicher Ereignisse interessante Einblicke bieten kann und weist m gliche Wege der empirischen Operationalisierung. Darüber hinaus ist der Band auch für Lesende empfehlenswert, die sich für die Ver nderungen diskursiver Strukturen in sozialen Ausnahmesituationen im Allgemeinen und für die gesellschaftliche Rahmung von Naturkatastrophen im Besonderen interessieren. URN: urn:nbn:de:0114-fqs070252 The volume edited by Dominik SCHRAGE documents the results of a research seminar held by the editor at the Department of Sociology, Technical University of Dresden, in the spring term of 2004 and fall term of 2004/05. The contributions are based mainly on discourse analysis of print media coverage of the Elbe flood in the summer of 2002. Topics include a reflection on the possibilities of implementing FOUCAULTian discourse theory within empirical research projects, as well as formal characteristics of the flood discourse, the mutual interference between the reports on the election campaigns for the Bundestag and on the flood, and finally the image of nature emerging within the flood discourse. The volume shows the potential of FOUCAULT's discourse analysis for current social events and outlines possible methodological implementations. Moreover, it is a recommended reading for those who are interested in changes in discursive structures within exceptional social circumstances in general and in the social framing of natural disaster in particular. URN: urn:nbn:de:0114-fqs070252 El volumen editado por Dominik SCHRAGE documenta el resultado de un seminario de investigación realizado por el mencionado editor en el departamento de sociología de la "Technical University of Dresden", a finales del verano de 2004. Las contribuciones se basan en análisis de la cobertura que realizó la prensa escrita durante las
Rahvusvahelise humanitaar iguse riigisisene rakendamine
Annika Talmar
Acta Societatis Martensis , 2010,
Abstract: International humanitarian law sets out rules to protect the victims of armed conflict and restrict the methods and means of warfare. It also establishes mechanisms to ensure that these rules are respected. One of the most important of these mechanisms is the universal jurisdiction of grave breaches. The main rules of international humanitarian law are enshrined in the four Geneva Conventions of 1949 and the two Additional Protocols of 1977. The 1954 Hague Convention for the Protection of Cultural Property in the Event of Armed Conflict provides for a comprehensive regime for the protection of cultural property. These instruments are at the heart of this article.Under the 1949 Geneva Conventions and their additional protocols states have an obligation to respect and ensure respect for the Conventions in all circumstances. Application of international humanitarian law presupposes the implementation of its rules by measures taken on national level. Such measures include: protection of the emblems; translation of the treaties into the national language; dissemination and training; experts and legal advisers; protection of cultural property and much more. The author analyses what if any national implementation measures have been taken in Estonia. Although Estonia claims to be a monist State and is generally very open to international law, introduction of international norms into municipal law does not necessarily make them applicable. Many of the provisions require specific legislative, administrative and practical measures to be adopted by a State to ensure application. The structure of this article is based on a report prepared by the International Committee of the Red Cross on the implementation of international humanitarian law in 1998.
Geschlechterdifferenzen und Geschlechtergrenzen. über die Verflechtung von Geschlecht, Raum und Erz hlung Gender Differences and Gender Limits. On the Link between Gender, Space, and Narrative
Annika Nickenig
querelles-net , 2008,
Abstract: Der vorliegende Sammelband beleuchtet aus verschiedenen Perspektiven die Verknüpfung von Geschlecht, Raum und Erz hlung und l st damit seine Forderung ein, Geschlecht als Analysekategorie im interdisziplin ren Forschungszusammenhang nutzbar zu machen. Die Prozesse der Konstruktion und Naturalisierung von Geschlecht werden in narratologischen und r umlichen Zusammenh ngen untersucht. Mit Raum‘ und Erz hlung‘ werden vor allem geographische und literaturwissenschaftliche Konzepte aufgerufen und miteinander verschr nkt. Die Beitr ge bewegen sich dabei konsequent an den R ndern der jeweiligen Disziplin und versuchen, das eigene Instrumentarium gegen den Strich zu bürsten, wodurch essentialistische Herangehensweisen vermieden werden. The collected volume at hand illuminates the connection between gender, space, and narrative from different perspectives and thus honors its intention of transforming gender into a useful category for analysis within interdisciplinary research. It examines the processes of construction and naturalization of gender in narratological and spatial contexts. In particular, the terms ’space’ and ‘narrative’ conjure up and entangle geographical and literary concepts. The contributions thus continuously move along the borders of the respective disciplines and attempt to go against the grain of their own analytical tools in order to avoid essentialist approaches.
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