OBJECTIVE 6R-5,6,7,8-tetrahydro-L-biopterin (6R-BH4) is a cofactor for endothelial nitric oxide synthase but also has antioxidant properties. Its stereo-isomer 6S-5,6,7,8-tetrahydro-L-biopterin (6S-BH4) and structurally similar pterin 6R,S-5,6,7,8-tetrahydro-D-neopterin (NH4) are also antioxidants but have no cofactor function. When endothelial nitric oxide synthase is 6R-BH4-deplete, it synthe...

Ischemia-reperfusion injury (IRI) due to hypotension is a common cause of human acute kidney injury (AKI). Hypoxia-inducible transcription factors (HIFs) orchestrate a protective response in renal endothelial and epithelial cells in AKI models. As human mucin 1 (MUC1) is induced by hypoxia and enhances HIF-1 activity in cultured epithelial cells, we asked whether mouse mucin 1 (Muc1) regulates ...

The role of monocytes/macrophages in the pathogenesis of ischemia-reperfusion injury (IRI) is unknown. We sought to determine whether activation of macrophage adenosine 2A (A(2A)) receptors (A(2A)Rs) mediates tissue protection. We subjected C57Bl/6 mice infused with clodronate [dichloromethylene bisphosphonate (Cl(2)MBP)] to IRI (32 min of ischemia followed by 24 h of reperfusion) to deplete th...

The effect of intravenous glucagon infusion on serum levels of immunoreactive GIP (IR-GIP), insulin (IRI), gastrin (IRG), and on blood glucose has been investigated in six healthy volunteers in the fasting state and during ingestion of a mixed standard meal. Glucagon (500 ng/kg/min) lowered significantly serum levels of IR-GIP and IRG below the fasting values and increased the levels of IRI and...

Understanding innate immune responses and their correlation to alloimmunity after solid organ transplantation is key to optimizing long term graft outcome. While Ischemia/Reperfusion injury (IRI) has been well studied, new insight into central mechanisms of innate immune activation, i.e. chemokine mediated cell trafficking and the role of Toll-like receptors have evolved recently. The mechanist...

PURPOSE To investigate the use of liposomal irinotecan (Irinophore C™) plus or minus 5-fluorouracil (5-FU) for the treatment of colorectal cancer. EXPERIMENTAL DESIGN The effect of irinotecan (IRI) and/or 5-FU exposure times on cytotoxicity was assessed in vitro against HT-29 or LS174T human colon carcinoma cells. The pharmacokinetics and biodistribution of Irinophore C™ (IrC™) and 5-FU, admi...

Hepatic ischemia and reperfusion injury (IRI) is an inflammatory condition and a significant cause of morbidity and mortality after surgery. Matrix metalloproteinases (MMPs) have been widely implicated in the pathogenesis of inflammatory diseases. Among the different MMPs, gelatinases (MMP-2 and MMP-9) are within the most prominent MMPs detected during liver IRI. While the role of MMP-9 in live...

Mononuclear cell infiltrates are found in human renal ischemia-reperfusion injury (IRI), and peritubular T lymphocytes have been identified in experimental IRI. However, the role of T cells in the pathogenesis of renal IRI is unknown. We hypothesized that T cells are one of the important mediators of renal IRI. To test this hypothesis, we used an established mouse model of renal IRI, and evalua...

BACKGROUND The protective role of IL-11, an IL-6 family cytokine, has been implicated in ischemia/reperfusion injury (IRI) in the heart and kidney, but its role has not been elucidated in liver IRI. This study was designed to evaluate the effects of IL-11 and its mechanism of action on liver IRI in a mouse model. METHODS A partial (70%) warm liver IRI was induced by interrupting the artery/po...

RATIONALE AND OBJECTIVE Vascular cell adhesion molecule-1 (VCAM-1) is upregulated in ischemia reperfusion injury (IRI), persisting after restoration of blood flow. We hypothesized that microparticles of iron oxide targeting VCAM-1 (VCAM-MPIO) would depict "ischemic memory" and enable in vivo assessment of VCAM-1 expression. METHODOLOGY AND FINDINGS Mice subject to unilateral, transient (30 mi...