Source:http://linkedlifedata.com/resource/pubmed/id/12609841
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2003-6-5
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| pubmed:abstractText |
In the pathogenesis of sepsis and disseminated intravascular coagulation (DIC), dysfunctional anticoagulant pathways are important. The function of the protein C system in DIC is impaired because of low levels of protein C and down-regulation of thrombomodulin. The administration of (activated) protein C results in an improved outcome in experimental and clinical studies of DIC. It is unknown whether congenital deficiencies in the protein C system are associated with more severe DIC. The aim of the present study was to investigate the effect of a heterozygous deficiency of protein C on experimental DIC in mice. Mice with single-allele targeted disruption of the protein C gene (PC+/-) mice and wild-type littermates (PC+/+) were injected with Escherichia coli endotoxin (50 mg/kg) intraperitoneally. PC+/-mice had more severe DIC, as evidenced by a greater decrease in fibrinogen level and a larger drop in platelet count. Histologic examination showed more fibrin deposition in lungs, kidneys, and liver in mice with a heterozygous deficiency of protein C. Interestingly, PC+/- mice had significantly higher levels of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, indicating an interaction between the protein C system and the inflammatory response. Survival was lower at 12 and 24 hours after endotoxin in the PC+/- mice. These results confirm the important role of the protein C system in the coagulative-inflammatory response on endotoxemia and may suggest that congenital deficiencies in the protein C system are associated with more severe DIC and adverse outcome in sepsis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Endotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrin,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinogen,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Protein C,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
101
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4823-7
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| pubmed:dateRevised |
2004-11-17
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| pubmed:meshHeading |
pubmed-meshheading:12609841-Animals,
pubmed-meshheading:12609841-Cytokines,
pubmed-meshheading:12609841-Disseminated Intravascular Coagulation,
pubmed-meshheading:12609841-Endotoxins,
pubmed-meshheading:12609841-Escherichia coli,
pubmed-meshheading:12609841-Fibrin,
pubmed-meshheading:12609841-Fibrinogen,
pubmed-meshheading:12609841-Heterozygote,
pubmed-meshheading:12609841-Interleukin-1,
pubmed-meshheading:12609841-Interleukin-6,
pubmed-meshheading:12609841-Kidney,
pubmed-meshheading:12609841-Liver,
pubmed-meshheading:12609841-Lung,
pubmed-meshheading:12609841-Mice,
pubmed-meshheading:12609841-Mice, Inbred C57BL,
pubmed-meshheading:12609841-Mice, Knockout,
pubmed-meshheading:12609841-Platelet Count,
pubmed-meshheading:12609841-Protein C,
pubmed-meshheading:12609841-Protein C Deficiency,
pubmed-meshheading:12609841-Tumor Necrosis Factor-alpha
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| pubmed:year |
2003
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| pubmed:articleTitle |
Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C-deficient mice.
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| pubmed:affiliation |
Department of Vascular Medicine/Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands. m.m.levi@amc.uva.nl
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| pubmed:publicationType |
Journal Article
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