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Sökning: id:"swepub:oai:DiVA.org:uu-381929" > PROTECTIVE EFFECTS ...

PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK

van Griensven, Martijn (författare)
Tech Univ Munich, Klinikum Rechts Isar, Dept Trauma Surg, Expt Trauma Surg, Munich, Germany,Technical University of Munich, Germany
Ricklin, Daniel (författare)
Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA;Univ Basel, Dept Pharmaceut Sci, Basel, Switzerland,University of Pennsylvania, USA ; University of Basel, Switzerland
Denk, Stephanie (författare)
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany,University of Ulm, Germany
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Halbgebauer, Rebecca (författare)
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany,University of Ulm, Germany
Braun, Christian K. (författare)
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany,University of Ulm, Germany
Schultze, Anke (författare)
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany,University of Ulm, Germany
Hoenes, Felix (författare)
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany,University of Ulm, Germany
Koutsogiannaki, Sofia (författare)
Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA,University of Pennsylvania, USA
Primikyri, Alexandra (författare)
Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA,University of Pennsylvania, USA
Reis, Edimara (författare)
Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA,University of Pennsylvania, USA
Messerer, David (författare)
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany,University of Ulm, Germany
Hafner, Sebastian (författare)
Univ Ulm, Inst Anaesthesiol Pathophysiol & Proc Dev, Ulm, Germany,University of Ulm, Germany
Radermacher, Peter (författare)
Univ Ulm, Inst Anaesthesiol Pathophysiol & Proc Dev, Ulm, Germany,University of Ulm, Germany
Biglarnia, Ali-Reza (författare)
Lund Univ, Malmo Univ Hosp, Dept Transplantat, Lund, Sweden,Malmö University Hospital ; Lund University
Resuello, Ranillo R. G. (författare)
Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines,Simian Conservation Breeding and Research Center (SICONBREC), Philippines
Tuplano, Joel V. (författare)
Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines,Simian Conservation Breeding and Research Center (SICONBREC), Philippines
Mayer, Benjamin (författare)
Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany,University of Ulm, Germany
Nilsson, Kristina, 1967- (författare)
Uppsala universitet,Experimentell och klinisk onkologi,Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC
Nilsson, Bo (författare)
Uppsala universitet,Klinisk immunologi,Uppsala University, Sweden
Lambris, John D. (författare)
Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA,University of Pennsylvania, USA
Huber-Lang, Markus (författare)
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany,University of Ulm, Germany
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 (creator_code:org_t)
Alphen aan den Rijn : LIPPINCOTT WILLIAMS & WILKINS, 2019
2019
Engelska.
Ingår i: Shock. - Alphen aan den Rijn : LIPPINCOTT WILLIAMS & WILKINS. - 1073-2322 .- 1540-0514. ; 51:1, s. 78-87
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course afterHS. Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated nonhuman primates (NHP; cynomolgusmonkeys) received a pressure-controlled severe HS (60min at mean arterial pressure 30 mmHg) with subsequent volume resuscitation. Thirty minutes after HS, animals were randomly treated with either an analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n =4) or with saline alone (n =4). The observation period lasted 300 min after induction of HS. We observed improved kidney function in compstatin Cp40-treated animals after HS as determined by improved urine output, reduced damage markers and a tendency of less histopathological signs of acute kidney injury. Sham-treated animals revealed classical signs ofmucosal edema, especially in the ileum and colon reflected by worsened microscopic intestinal injury scores. In contrast, Cp40-treated HS animals exhibited only minor signs of organ edema and significantly less intestinal damage. Furthermore, early systemic inflammation and coagulation dysfunction were both ameliorated by Cp40. The data suggest that therapeutic inhibition of C3 is capable to significantly improve immune, coagulation, and organ function and to preserve organ-barrier integrity early after traumatic HS. C3-targeted complement inhibition may therefore reflect a promising therapeutic strategy in fighting fatal consequences of HS.

Ämnesord

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Nyckelord

Complement
hemorrhagic shock
inflammation
intestine
kidney
nonhuman primate
Immunologi

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

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