Surgery
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Bone marrow mesenchymal stem cells (MSCs) may mediate their beneficial effects by paracrine mechanisms. Recently, we reported that tumor necrosis factor-alpha (TNF-alpha) increased the release of vascular endothelial growth factor (VEGF) from human MSCs and augmented transforming growth factor-alpha (TGF-alpha)-stimulated VEGF secretion. However, it is unknown whether TNF-alpha stimulates VEGF production via TNF receptor 1 (TNFR1) or 2 (TNFR2) and the mechanism by which TNF-alpha augments TGF-alpha (a ligand of epidermal growth factor receptor, EGFR) stimulated VEGF production. We hypothesized that the ablation of TNFR2 would decrease TNF-alpha-stimulated and/or TGF-alpha- stimulated VEGF production via MEK-dependent mechanisms. ⋯ TNFR2 plays a vital role in the effects of TNF-alpha and TGF-alpha on MSC VEGF production. The activation of MEK was implicated in this novel cross talk between TNFR2 and TGF-alpha-EGFR in regulating the production of VEGF in human MSCs.
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We have demonstrated previously that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival in lethal models of hemorrhagic shock. This study investigated whether VPA treatment would improve survival in a clinically relevant large animal model of poly-trauma/hemorrhagic shock, and whether the protective effects are executed through the Akt survival pathway. ⋯ Treatment with VPA without blood transfusion improves early survival in a highly lethal poly-trauma and hemorrhagic shock model. The survival advantage is due not to improvement in resuscitation but to better tolerance of shock by the cells, in part due to the preservation of the Akt survival pathway.
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The aim of the current study was to determine the role of heparin-binding (HB) epidermal growth factor (EGF)-like growth factor as a mediator of gut barrier function after hemorrhagic shock and resuscitation (HS/R) in mice. ⋯ HB-EGF is essential for the preservation of gut barrier function after HS/R. These findings support the clinical use of HB-EGF in protection of the intestines from disease states associated with intestinal hypoperfusion injury.
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Although many surgical innovations are said to "shorten recovery," recovery has not been consistently defined or measured. The goal of this study was to assess the validity of a physical activity questionnaire (The Community Health Activities Model Program for Seniors [CHAMPS]) as an indicator of postoperative recovery. ⋯ Evidence is provided for construct validity for a physical activity questionnaire as a measure of surgical recovery.
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We previously evaluated cardioprotective effects of glucose-insulin-potassium (GIK) in a porcine ischemia-reperfusion model; our results showed less myocardial pH decrease during ischemia and reperfusion and faster normalization of ATP and glucose during reperfusion. The proposed protective mechanism was facilitation of glucose transport for myocardial metabolism. The objective of this study was to assess the impact of insulin-potassium (IK) alone on myocardial metabolism. ⋯ IK infusion alone demonstrates cardioprotective effects during early ischemia; however, compared to GIK infusion after 20 minutes of ischemia and reperfusion, myocardial pH and glucose levels were not sustained. Although insulin may facilitate glucose transport during ischemia, additional glucose in combination with IK enhances myocardial protection during reperfusion. This finding suggests that GIK enhancement during acute ischemia-reperfusion may improve myocardial protection.