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Brain Death-Induced Inflammatory Activity in Human Pancreatic Tissue: A Case-Control Study.
MedLine Citation:
PMID:  24142035     Owner:  NLM     Status:  Publisher    
BACKGROUND: Long-term insulin independence after islet transplantation depends on engraftment of a large number of islets. However, the yield of pancreatic islets from brain-dead donors is negatively affected by the up-regulation of inflammatory mediators. Brain death is also believed to increase tissue factor (TF) expression, contributing to a low rate of engraftment.
METHODS: We conducted a case-control study to assess brain death-induced inflammatory effects in human pancreas. Seventeen brain-dead patients and 20 control patients undergoing pancreatectomy were studied. Serum tumor necrosis factor (TNF), interleukin (IL) 6, IL-1β, interferon (IFN) γ, and TF were measured using enzyme-linked immunosorbent assay kits. Gene expressions of these cytokines and TF were evaluated by reverse transcriptase quantitative polymerase chain reaction. Protein quantification was performed by immunohistochemistry in paraffin-embedded pancreas sections.
RESULTS: Brain-dead patients had higher serum concentrations of TNF and IL-6 and increased TNF protein levels compared to controls. The groups had similar TNF, IL-6, IL-1β, and IFN-γ messenger RNA levels in pancreatic tissue. Reverse transcriptase quantitative polymerase chain reaction revealed TF messenger RNA up-regulation in controls. Immunohistochemical analyses showed that brain-dead patients had increased TNF protein levels compared to controls.
CONCLUSIONS: Brain death induces inflammation evidenced by the up-regulation of TNF in serum and pancreatic tissue. Blocking the expression of key inflammatory mediators in brain-dead donors should be evaluated as a new approach to improve the outcomes of islet transplantation.
Tatiana H Rech; Daisy Crispim; Jakeline Rheinheimer; Sabrina S Barkan; Alessandro B Osvaldt; Tomaz J M Grezzana Filho; Cleber R P Kruel; Juliano Martini; Jorge L Gross; Cristiane B Leitão
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-10-17
Journal Detail:
Title:  Transplantation     Volume:  -     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 Division of Intensive Care Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 2 Laboratory of Human Islet Biology, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 3 Division of Surgery, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 4 Address correspondence to: Tatiana Helena Rech, Ph.D., Division of Intensive Care Medicine of Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 13° andar, 90035-003, Porto Alegre-RS, Brazil.
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