Neutrophil-mediated lung injury is a cause of significant morbidity and mortality in patients with multiple injuries. We have shown previously that fracture hematoma can activate neutrophils and is thus a putative mediator of the systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF) in those patients with severe skeletal trauma. Our aim was to establish a rodent model of fracture which caused lung injury and subsequently to administer a drug following fracture to attenuate the lung injury. The drug we chose was N-acetylcysteine, a potent antioxidant.Adult Sprague-Dawley rats were assigned to 4 groups: (1) general anesthetic only, (2) general anesthetic with bilateral femur fractures and nailing, (3) general anesthetic and N-acetylcysteine, (4) general anesthetic with bilateral femur fractures and nailing and N-acetylcysteine after the injury (n = 6 in each group). The dose of N-acetylcysteine was 0.5 mg/kg which was given intraperitoneally after injury to the treated groups. The rats were killed 24 hours after injury and some parameters of lung injury were evaluated--i.e., bronchoalveolar lavage (BAL), lung tissue myeloperoxidase levels (MPO) and wet/dry ratios of lung tissue. The results were analyzed, using one-way analysis of variance.Bilateral femur fracture produced a significant lung injury, measured by increases in MPO (25-43 microg/g tissue) and BAL protein (460-605 microg/mL). This effect was attenuated by treatment with N-acetylcysteine (MPO 43-9 microg/mL, BAL protein 605-198 microg/mL).N-acetyl cysteine, if given after skeletal trauma, is of potential therapeutic benefit, in preventing SIRS, ARDS and MOF.
Background. Normal cells undergo contact inhibition of growth when their surface molecules interact. Tumor cells, however, have undergone a mutation that prevents this arrest of growth upon contact inhibition and allows constant growth. Thus, growth inhibition fails to occur despite the interaction of surface molecules. In recent years a subgroup of these surface molecules has been of interest to cancer investigators. This subgroup has been termed the tumor rejection antigens (TRAs). As the name implies, these are specific to the tumor of origin and may direct the immune system of the host to target the tumor cells and kill them. Methods. A literature search was carried out on TRAs to ascertain the current thinking on the subject. Results. Initial studies of TRAs have revealed that some of them may be heat shock proteins (HSPs). In particular, grp96, a number of the HSP90 family, has been implicated. More recent studies, however, have shown that HSPs alone may not be immunogenic but may act as carrier proteins for tumor specific peptides. Conclusion. Such findings have led to speculation that HSPs or their associated peptides may have a role in the diagnosis and/or treatment of specific cancers. Immunotherapy and bispecific antibodies in particular are areas in which HSPs may prove to be useful. Cancer 1995;75:2649–55.
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