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Identifier 000410276
Title Η έκφραση των υποδοχέων των γλυκοκορτικοειδών στα περιφερικά μονοπύρηνα αίματος σε συσχέτιση με την διέγερση του άξονα και των πρωτεϊνών στρες hsp70 και hsp90 σε ασθενείς ΜΕΘ με σήψη ή τραύμα
Alternative Title Clucocorticoid receptor expression in peripheral blood mononuclear cells in association to hpa-axis stimulation and hsp70 and hsp90 expression in icu patients with sepsis or trauma
Author Βάρδας, Κωνσταντίνος Γ.
Thesis advisor Μπριασούλης, Γεώργιος
Reviewer Νάνας, Σεραφείμ
Χαρμανδάρη Ευαγγελία
Σαμώνης, Γεώργιος
Γαλανάκης, Εμμανουήλ
Δημητρίου, Ελένη
Βενυχάκη, Μαρία
Abstract Purpose: To examine if the human glucocorticoid receptor (hGR) isoform-α mRNA and hGR protein expressions are deficient in the acute phase of sepsis (S) compared to systemic inflammatory response syndrome (SIRS) and healthy subjects (H). To evaluate if the hGRα and hGR alterations are associated with cortisol changes, and if they are related to: 1) extracellular and intracellular heat shock proteins (HSP) 72 and 90α; 2) ACTH, prolactin, and interleukins (ILs); 3) the outcome. Methods: Patients consecutively admitted to a University Hospital Intensive Care Unit (ICU) with S (n=48) or SIRS (n=40) were enrolled in the study. Thirty-five H were also included. Total mRNA was isolated from peripheral blood samples and cDNA was prepared. RT-PCR was performed. Intracellular hGR and HSPs expression in monocytes and/or neutrophils was evaluated using 4-colour flow cytometry. Serum prolactin, ACTH and cortisol concentrations were also measured. ELISA was used to evaluate serum ILs and extracellular (e) HSPs (eHSP72, eHSP90α). Results: hGR protein was higher in S compared to H and SIRS; hGRα mRNA was higher in S compared to H (p<0.05). In sepsis, hGR protein and eHSP72 were higher among non-survivors compared to survivors (p<0.05). The hGR MFI and hGRα mRNA fold change were significantly related to each other (rs=0.64, p<0.001). Monocyte hGR protein expression was positively correlated to extracellular and intracellular HSPs, cortisol, and ILs and negatively to organ dysfunction (p<0.05). HSPs, hGR, and cortisol were able to discriminate sepsis from SIRS (AUROC >0.85, p<0.05). In sepsis, monocyte-hGR protein and eHSP72 were strong predictors of mortality (AUROC >0.95 p<0.04). Conclusions: Acute-phase sepsis is associated with increased hGR expression and cortisol concentrations, possibly implying no need for exogenous steroids. At this stage, hGR is able to predict sepsis and outcome, and is related to stress-activated bio-molecules and organ dysfunction.
Language Greek
Issue date 2017-07-26
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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