Haemostatic products as a potential therapy for vesicant-contaminated wounds

Published on Dec 1, 2012
Charlotte Amy Hall1
Estimated H-index: 1
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Abstract
There is potential for haemorrhaging injuries that become contaminated with toxic chemicals e.g. sulphur mustard (SM). There are no specific medical countermeasures for such injuries at present. It is proposed that haemostats could simultaneously stop bleeding and decontaminate wounds. Products must be able to clot SM-contaminated blood and reduce SM percutaneous absorption to be considered suitable. Sulphur mustard did not significantly affect coagulation in vitro or in vivo. Overall SM did not affect the pro-coagulatory function of haemostats. However, clot strength in WoundStat™ treated blood was adversely affected by SM in vitro. Superficial damage to the skin significantly increased the percutaneous absorption of SM with good agreement between in vitro and in vivo studies. Moreover, the altered toxicodynamics imply that the latent period associated with SM pathology is due, in part, to rate of absorption and not solely caused by biochemical pathways. Application of WoundStat™ significantly reduced the amount and rate of SM penetration through the skin in vitro. Furthermore, WoundStat™ reduced SM percutaneous absorption and pathology in vivo. Microarray analysis has identified that SM exposure via damaged skin causes changes in gene expression which may warrant further investigation as potential therapeutic targets.
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#1Hiroshi Kawasaki (Keio: Keio University)H-Index: 14
#2Keisuke Nagao (Keio: Keio University)H-Index: 26
Last. Masayuki Amagai (Keio: Keio University)H-Index: 92
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Background Loss-of-function mutations in filaggrin are major predisposing factors for atopic dermatitis. Although various reports suggest a critical role for filaggrin in stratum corneum (SC) barrier formation, the lack of filaggrin-null ( Flg −/− ) mice has hampered detailed in vivo analysis of filaggrin's functions. Objective We sought to generate Flg −/− mice and to assess the effect of filaggrin loss on SC barrier function and percutaneous immune responses. Methods We generated Flg −/− mice ...
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Macrophages altered by various Th2-associated and anti-inflammatory mediators – including IL-4 and IL-13 [inducing alternatively activated macrophages (AAMs)], IL-10 and TGF-β– were generically termed M2. However, markers that discriminate between AAMs and other M2 remain scarce. We previously described E-cadherin as a marker for AAMs, permitting these macrophages to fuse upon IL-4 stimulation. To identify novel potential contributors to macrophage fusion, we assessed the effect of IL-4 on other...
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Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis
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Abstract: Skin is important for the absorption and metabolism of exposed chemicals such as cosmetics or pharmaceuticals. The Seventh Amendment to the EU Cosmetics Directive prohibits the use of animals for cosmetic testing for certain endpoints, such as genotoxicity; therefore, there is an urgent need to understand the xenobiotic metabolizing capacities of human skin and to compare these activities with reconstructed 3D skin models developed to replace animal testing. We have measured Phase I en...
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Abstract The most important function of the skin is the formation of a barrier between the "inside" and the "outside" of the organism, which prevents invasion of pathogens and fends off chemical assaults as well as the unregulated loss of water and solutes. The physical barrier is mainly localized in the stratum corneum, which consists of protein-enriched cells and lipid-enriched intercellular domains. Any modifications in epidermal differentiation and lipid composition results in altered barrie...
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The nuclear receptor coactivator amplified in breast cancer 1 (AIB1/SRC-3) has a well-defined role in steroid and growth factor signaling in cancer and normal epithelial cells. Less is known about its function in stromal cells, although AIB1/SRC-3 is up-regulated in tumor stroma and may, thus, contribute to tumor angiogenesis. Herein, we show that AIB1/SRC-3 depletion from cultured endothelial cells reduces their proliferation and motility in response to growth factors and prevents the formation...
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Abstract Sulphur mustard (SM) is a blistering agent that causes debilitating damage to the skin, eyes and respiratory system. In cases of severe exposure, immunodepletion can occur as well as death, due to secondary infections. The toxicity of SM is thought to be mediated in part by the alkylation of nucleic acids and proteins, although the exact mechanisms are not clear. In addition, although the first known use of SM was in military conflict nearly 100 years ago, there are still no effective t...
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The inverse correlation between DNA methylation and lineage-specific gene expression during T helper cell development is well documented. However, the specific functions of the de novo methyltransferases Dnmt3a and Dnmt3b in cytokine gene regulation have not been defined. We demonstrate that the expression of Dnmt3a and Dnmt3b are induced to a greater extent in T helper 2 (Th2) cells than in T helper 1 cells during polarization. Using conditional mutant mice, we determined that Dnmt3a, but not D...
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Dermal absorption may represent the predominant route of entry for agrochemicals and so effective methods for skin cleansing (decontamination) are integral to maintaining the health of those involved in the production and use of agrochemicals. In practical terms, the skin decontamination of agrochemicals can be considered a facet of personal hygiene, attained through hand-washing and a change of clothing. Whilst it has long been recognised that decontamination is most effective when performed im...
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The use of haemostatic materials that could be used to mitigate against the effects of the chemical warfare agent soman (GD) on contaminated personnel that may also present with wounds were investigated. To support the in vitro diffusion cell component of this work, the penetration rate of \(^1\)\(^4\)C-GD into different receptor fluids was evaluated to enable determination of the most appropriate receptor fluid to use as a sink for GD. Of the receptor media evaluated only 50% aqueous ethanol wa...
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