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- Laschke, Mattias W, et al.
(author)
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Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice.
- 2007
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In: American Journal of Physiology: Gastrointestinal and Liver Physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 292, s. 1396-1402
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Journal article (peer-reviewed)abstract
- Cholestasis is a major complication in sepsis although the underlying mechanisms remain elusive. The aim of this study was to evaluate the role of P-selectin and leukocyte recruitment in endotoxemia- associated cholestasis. C57BL/6 mice were challenged intraperitoneally with endotoxin ( 0.4 mg/ kg), and 6 h later the common bile duct was cannulated for determination of bile flow and biliary excretion of bromosulfophthalein. Mice were pretreated with an anti-P-selectin antibody or an isotype- matched control antibody. Leukocyte infiltration was determined by measuring hepatic levels of myeloperoxidase. Tumor necrosis factor-alpha and CXC chemokines in the liver was determined by ELISA. Liver damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. Apoptosis was quantified morphologically by nuclear condensation and fragmentation using Hoechst 33342 staining. Endotoxin induced a significant inflammatory response with increased TNF-alpha and CXC chemokine concentrations, leukocyte infiltration, liver enzyme release, and apoptotic cell death. This response was associated with pronounced cholestasis indicated by a > 70% decrease of bile flow and biliary excretion of bromosulfophthalein. Immunoneutralization of P-selectin significantly attenuated endotoxin- induced leukocyte infiltration reflected by a > 60% reduction of hepatic myeloperoxidase levels. Interference with P-selectin decreased endotoxin- mediated hepatocellular apoptosis and necrosis, but did not affect hepatic levels of tumor necrosis factor-alpha and CXC chemokines. Of interest, inhibition of P- selectin restored bile flow and biliary excretion of bromosulfophthalein to normal levels in endotoxin- challenged animals. Our study demonstrates for the first time that P-selectin-mediated recruitment of leukocytes, but not the local production of proinflammatory mediators, is the primary cause of cholestasis in septic liver injury.
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| 6. |
- Lindell, Bengt, 1955-
(author)
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Notorietet och kontradiktion
- 2007. - 1
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Book (other academic/artistic)abstract
- I boken behandlas vilka omständigheter som är så allmänt veterliga att en domstol utan kommunikation kan lägga dem till grund för avgörandet.
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| 7. |
- Lindell, Bengt, redaktör, författare, 1955-, et al.
(author)
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Straffprocessen
- 2007. - 1
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Book (other academic/artistic)
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| 8. |
- Marklund, Linda, 1975-
(author)
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Skolmedling i teori och praktik
- 2007
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Licentiate thesis (other academic/artistic)abstract
- This thesis aims to answer the questions; what and were does peer mediation fit into the theoretical and practical frameworks of mediation? How does peer mediation fit into the retributive legal system as it stands today? What problems can arise with the use of peer mediation, its organizations and with the use of adolescent peer mediators, in a legal perspective? When it comes to the question of where peer mediation has its theoretical framework the hypothesis in this thesis are that peer mediation, with respect to the practical framework, is a hybrid of the settlement driven mediation and the transformative mediation. The theoretical framework comes from the philosophy of restorative justice (RJ), primarily the victim-offender mediation in the sense that if peer mediation per se is not enough it has to bee a whole school approach for it to work. In RJ, the community is as important as the primarily parties, the offender and the offended. In school conflicts, the community is the whole school, and as such it has to bee the whole school that is involved in the conflict management program. The method used in this thesis is the traditional method of jurisprudence combined with two case studies. The first case study is the "Peer mediations Project" that in fact was the starting point for the research. The aim with this case study is too show how peer mediation can work in Sweden, both on an organizational and a practical level. In doing so it also highlights which legal questions that is relevant for this thesis. The second case study is the "Spice conflict". This case study aims to make researcher go deeper in the legal issues as well as to illuminate a school conflict and how it can progress. The fist chapter gives a background for peer mediation and the focus of this thesis, as well as the first contact with the two case studies. Chapter two gives a legal background for the thesis. Chapter three deals with conflict theory and chapter four with schools conflicts and the different programs there is to handle those conflicts. In chapter five the different mediations models are presented more in depth and discussed from at mediation perspective. Chapter six goes deeper into the second case study in an effort to resolve the legal issues that has arisen. In the last chapter there is a discussion which originates from the five Nordic principles of mediation, facilitative, peaceably, freely, confidently and restoratively, in conjunction whit mediation, conflict and legal theory.
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