The Journal of surgical research
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Severe acute pancreatitis (AP)(2) is associated with exaggerated leukocyte adherence and activation. Endothelial cellular adhesion molecules (CAMs) can be induced by cytokines, but also directly by oxygen free radicals (OFRs), mediated by nuclear factor kappa-B (NF-kappa B). We investigated the behavior of inducible CAMs in relation to pancreatic oxidative stress. Our novel modification of cerium capture histochemistry (reaction of OFRs with cerium produces laser reflective Ce perhydroxide precipitates) combined with reflectance confocal laser scanning microscopy (CLSM) allows the histological codemonstration of in vivo OFR production and immunolabeled CAMs, or NF-kappa B. ⋯ The early acinar oxidative stress is colocalized with NF-kappa B activation, preferential P-selectin, and ICAM upregulation in this AP model. Subsequently, adherent, activated PMNs become the major source of OFRs, thereby contributing to tissue damage.
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Dimethyl sulfoxide (DMSO) is a potent antioxidant which protects against endotoxemia and septic shock in animal models. We investigated the therapeutic effect of DMSO on intercellular adhesion molecule 1 (ICAM-1) gene expression and activation of nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) in a rat model of peritonitis sepsis. This postchallenge model simulates the clinical treatment of ruptured viscus peritonitis. ⋯ Therapeutic treatment of DMSO inhibited sepsis-induced activation of NF-kappaB and AP-1, resulting in the suppression of ICAM-1 gene expression in the livers of peritonitis septic rats. This finding suggests that reactive oxidants are involved in the signal transduction pathways for activation of NF-kappaB and AP-1. Thus, antioxidants which inhibit NF-kappaB and AP-1 activation may be beneficial in treating sepsis and septic shock.
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Various topical hemostatic agents or devices have been employed to address the challenges associated with hemorrhage from parenchymal organs during surgery or trauma. Their relative efficacy, however, has not been assessed in a single animal model. The objective of this study was to develop a small animal renal hemorrhage model for comparing hemostatic efficacy of various topical agents, and then to compare fibrin sealant (FS) to an existing standard of care for topical hemostasis. ⋯ Both FS groups had significantly less blood loss, longer survival times, and maintained higher MAPs than the GS-treated groups. Quantitative dose effects and functional deficiencies in topical hemostatic products could be assessed using this animal model. The study demonstrated that liquid FS was significantly more efficacious than a GS soaked in thrombin for abating hemorrhage from a renal excision in a heparinized rat.
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The aim of this study was to define whether veterans who survived repair of ruptured abdominal aortic aneurysms (AAA) experienced late survival rates similar to those surviving repair of intact AAA. ⋯ In addition to higher postoperative mortality rates with ruptured AAA, mortality during follow-up for survivors of AAA repair was also greater for those who survived repair of ruptured AAA. The toll taken by ruptured abdominal aortic aneurysms did not end in the immediate postoperative period.
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Ischemic preconditioning (IPC) protects myocardium from ischemia reperfusion injury by activating mitochondrial K(ATP) channels. However, the mechanism underlying the protective effect of K(ATP) channel activation has not been elucidated. It has been suggested that activation of mitochondrial K(ATP) channels may prevent mitochondrial dysfunction associated with Ca(2+) overload during reperfusion. ⋯ Pinacidil depolarized inner mitochondrial membrane, as evidenced by decreased RCI and increased state 2 at baseline. Depolarization may decrease Ca(2+) influx into mito, protecting mito from Ca(2+) overload, as evidenced by improved state 3 and RCI at high Ca(2+) concentrations. The myocardial protective effects resulting from activating K(ATP) channels either pharmacologically or by IPC may be the result of protecting mito from Ca(2+) overload.