Haemostatic products as a potential therapy for vesicant-contaminated wounds

Published on Dec 1, 2012
Charlotte Amy Hall1
Estimated H-index: 1
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.
#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 ...
#1J. Van den Bossche (Vrije Universiteit Brussel)H-Index: 1
#2Damya Laoui (Vrije Universiteit Brussel)H-Index: 28
Last. J. Van Ginderachter (Vrije Universiteit Brussel)H-Index: 4
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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...
#1Julie A. Brazzatti (University of Adelaide)H-Index: 7
#2Manuela Klingler-Hoffmann (University of Adelaide)H-Index: 16
Last. Shaun R. McColl (University of Adelaide)H-Index: 74
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Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis
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#2Joo Eun Jung (Stanford University)H-Index: 18
Last. Pak H. Chan (Stanford University)H-Index: 119
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Oxidative stress and glucose affect the expression of various genes that contribute to both reactive oxygen species generation and antioxidant systems. However, systemic alteration of oxidative stress-related gene expression in normal brains and in brains with a high-glucose status after ischemic–reperfusion has not been explored. Using a polymerase chain reaction array system, we demonstrate that thioredoxin-interacting protein (Txnip) is induced by both oxidative stress and glucose. We found t...
#1Christine Götz (HHU: University of Düsseldorf)H-Index: 8
#2Roland Pfeiffer (HHU: University of Düsseldorf)H-Index: 3
Last. Ellen Fritsche (HHU: University of Düsseldorf)H-Index: 39
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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...
#1Adone Baroni (Seconda Università degli Studi di Napoli)H-Index: 27
#2Elisabetta Buommino (Seconda Università degli Studi di Napoli)H-Index: 23
Last. Ronni Wolf (Kaplan Medical Center)H-Index: 36
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#1Maram Al-Otaiby (Georgetown University)H-Index: 2
#2Elena Tassi (Georgetown University)H-Index: 18
Last. Anton Wellstein (Georgetown University)H-Index: 67
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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...
#1Paul A. Jowsey (Newcastle University)H-Index: 12
#2Faith M. Williams (Newcastle University)H-Index: 4
Last. Peter G. Blain (Newcastle University)H-Index: 29
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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...
#1A.A. BrimfieldH-Index: 1
#2S.D. SoniH-Index: 1
Last. J.S. GrahamH-Index: 1
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Abstract We recently published electron paramagnetic resonance (EPR) spin trapping results that demonstrated the enzymatic reduction of sulfur mustard sulfonium ions to carbon-based free radicals using an in vitro system containing sulfur mustard, cytochrome P450 reductase, NADPH, and the spin trap α-(4-pyridyl-1-oxide)- N - tert -butylnitrone (4-POBN) in buffer (A.A. Brimfield et al., 2009, Toxicol. Appl. Pharmacol. 234:128–134). Carbon-based radicals have been shown to reduce molecular oxygen ...
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#2Baohua ZhouH-Index: 26
Last. Mark H. KaplanH-Index: 73
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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...
Cited By2
#1Robert P. Chilcott (University of Hertfordshire)H-Index: 23
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...
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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