Here's what I've been writing up this week. This is how exciting life is as a biochemist.... :no::
Section A. Specific Aims
The most likely scenarios resulting in mass casualties from a radiological event involve either detonation of a nuclear weapon or the use of a radiological dispersal device (RDD), or “dirty bombâ€. In either case, casualties are expected to suffer from a combination of injuries, consisting of radiation exposure in addition to burns, bleeding, blunt force trauma and infection. Because the prognosis for all combined injuries (CI) is worse than for radiation injury (RI) alone, strategies for reducing the synergistic effects of CI must be sought. Unfortunately, the mechanism(s) underlying sensitization to radiation by additional trauma are poorly understood and, as a result, there are currently no medical countermeasures for CI. Our long term goal is to develop a successful regimen to mitigate or reverse the physiological consequences of CI.
CI casualties suffer from numerous and extensive physical impairments, including reduced hematopoiesis, susceptibility to bacterial infection, delayed wound healing and multiple organ failure. These conditions originate at the cellular level, with CI challenged cells exhibiting dramatic changes in their gene expression profiles, including increases in inducible nitric oxide synthase (iNOS), cytokines, extracellular matrix proteins, toll-like receptor signaling and Wnt-mediated JUNK signaling, along with a concurrent decrease in cell-cell adhesion proteins. Some genes that are modulated in response to CI are also affected by RI alone. For instance, upregulation of iNOS has been linked to radiation-induced, cell apoptosis. In the case of RI, inhibition of iNOS, COX-2, or cytokine production, or treatment with antibiotics prior to exposure have been shown to confer radioprotection. However, these manipulations do not treat or mitigate the detrimental effects of CI.
Because morbidity arising from CI is due mainly to cell death, the primary goal during post-exposure stabilization is to replace or repair damaged tissue as quickly as possible. It is evident that an i.v. injection of bone marrow mesenchymal stem cells (BMSCs) ameliorates RI in mice. We hypothesize the BMSCs may provide a therapeutic modality whereby damaged tissues can be directly repaired or regenerated.
Section A. Specific Aims
The most likely scenarios resulting in mass casualties from a radiological event involve either detonation of a nuclear weapon or the use of a radiological dispersal device (RDD), or “dirty bombâ€. In either case, casualties are expected to suffer from a combination of injuries, consisting of radiation exposure in addition to burns, bleeding, blunt force trauma and infection. Because the prognosis for all combined injuries (CI) is worse than for radiation injury (RI) alone, strategies for reducing the synergistic effects of CI must be sought. Unfortunately, the mechanism(s) underlying sensitization to radiation by additional trauma are poorly understood and, as a result, there are currently no medical countermeasures for CI. Our long term goal is to develop a successful regimen to mitigate or reverse the physiological consequences of CI.
CI casualties suffer from numerous and extensive physical impairments, including reduced hematopoiesis, susceptibility to bacterial infection, delayed wound healing and multiple organ failure. These conditions originate at the cellular level, with CI challenged cells exhibiting dramatic changes in their gene expression profiles, including increases in inducible nitric oxide synthase (iNOS), cytokines, extracellular matrix proteins, toll-like receptor signaling and Wnt-mediated JUNK signaling, along with a concurrent decrease in cell-cell adhesion proteins. Some genes that are modulated in response to CI are also affected by RI alone. For instance, upregulation of iNOS has been linked to radiation-induced, cell apoptosis. In the case of RI, inhibition of iNOS, COX-2, or cytokine production, or treatment with antibiotics prior to exposure have been shown to confer radioprotection. However, these manipulations do not treat or mitigate the detrimental effects of CI.
Because morbidity arising from CI is due mainly to cell death, the primary goal during post-exposure stabilization is to replace or repair damaged tissue as quickly as possible. It is evident that an i.v. injection of bone marrow mesenchymal stem cells (BMSCs) ameliorates RI in mice. We hypothesize the BMSCs may provide a therapeutic modality whereby damaged tissues can be directly repaired or regenerated.
