The Journal of surgical research
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Tissue factor (TF) is an initiator of coagulation. The serine protease factor Xa (FXa) is the convergence point of the extrinsic and intrinsic components of the coagulation cascade. In addition to its hemostatic function, FXa elicits inflammatory responses in endothelial cells that may be important in surgical procedures in which inflammation is triggered. This study tested the hypothesis that FXa can up-regulate TF on vascular endothelial cells by a mitogen-activated protein kinase (MAPK)- and NF-κB-dependent pathway. ⋯ (1) FXa up-regulates TF protein expression and activity in HUVECs, (2) FXa-induced up-regulation of TF is independent of the thrombin-PAR1 pathway, and (3) the MAPK and NF-κB pathways, but not PI3 kinase pathway, are involved in FXa-induced TF expression on human umbilical endothelial cells. FXa may be a feed-forward alternative mechanism of activating TF expression and activity, thereby increasing a procoagulant state or inflammation. This mechanism may be important in the pro-inflammatory state initiated by cardiac surgical procedures.
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Mouse models are of increasing interest to study cellular and molecular mechanisms during fracture healing. However, unlike in large animals and in humans, stable fixation of fractures has been difficult due to the small size of the mouse. ⋯ The LockingMouseNail allows standardized fixation of mouse femur fractures and also stabilization of segmental defects. By introducing different gap sizes, the healing process can be influenced, ranging from normal fracture healing to atrophic non-union formation. Therefore, the model may ideally be suited to study molecular mechanisms of normal fracture healing, delayed healing, and non-union formation. It may additionally allow studying biological properties and effectiveness of different bone substitutes in stabilized segmental defects.
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Alternative experimental models of hemorrhage mimic particular conditions of clinical settings and provide advantages to analyze novel resuscitation treatments. Here, we compared alternative models of hemorrhage and analyzed the effects of resuscitation with Hextend. ⋯ The survival benefits of resuscitation with Hextend depended on the experimental models and did not correlate with blood chemistry, hemodynamic, or serum cytokine levels. However, resuscitation with Hextend inhibited TNF levels in the lung and the liver with a pattern that resembled the survival benefits.
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Paraplegia is one of the most common complications following aortic aneurismal surgery. The present study examined the hypothesis that neuroprotection of sevoflurane postconditioning (PostC) against spinal cord reperfusion injury is associated with free radicals-mediated up-regulation of antioxidant enzymes in rabbits. ⋯ An initial oxidative stress, as a trigger to up-regulate the antioxidant enzyme activities, plays an important role in the protection of sevoflurane PostC against spinal cord reperfusion injury.