Biomolecular Analysis of Beta Dose-Dependent Cutaneous Radiation Injury in a Porcine Model

Burnett, Luke; Gabard, Alexis R.; Robinson, Mac; Bourland, J. Daniel; Dorand, Jennifer E.; Dozier, Stephen; Xiao, Roy; Roy, Daniel; Tytell, Michael

doi:10.1667/rr14283.1

Cited by 8 publications

(11 citation statements)

References 48 publications

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“…CRI symptoms progress reliably from epidermal degradation to moist desquamation with exposure to doses in excess of 24 Gy. The progression of CRI is most pronounced at the highest radiation doses, with scabbing noted between þ 35 and þ46 days postirradiation (107). A unique, on-screen image-scoring technique is conducted using both an erythema and moist desquamation scale, with a consensus score then derived.…”

Section: Session 2: Radiation Sources and Animal Models Of Cutaneous mentioning

confidence: 99%

“…Data from well-established animal models can be translated to better understand similar injuries in humans. One such animal model, the Yorkshire swine [presented in Session 2 (107)], was administered radiation at multiple doses using beta, orthovoltage X-ray or linear accelerator. As described above, observations and histological data show radiation dose-dependent evolution of skin pathology over time, including the diminishing, then absent, basal cell population by day 70 (107).…”

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

“…One such animal model, the Yorkshire swine [presented in Session 2 (107)], was administered radiation at multiple doses using beta, orthovoltage X-ray or linear accelerator. As described above, observations and histological data show radiation dose-dependent evolution of skin pathology over time, including the diminishing, then absent, basal cell population by day 70 (107). The severity of skin reactions was assessed using a modified methodology and acute skin injury scale (148).…”

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

“…Alpha-catenin sits at the junction of intercellular adhesion, coordinating activity between cells. Electron microscopy of the intercellular components of the skin shows the major cellular junctions and desmosomes (150), which are known to be adversely affected by ionizing radiation (107). For this reason, KeraStat Cream (containing purified, human-derived keratin) has been tested for its ability to manage both porcine and human skin injuries, in the hopes that the application of human-derived keratin, the main skin protein, will create an environment supportive of healing.…”

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

“…For example, in the large swine model of irradiated skin, metabolomic analysis revealed dose-and time-dependent changes in several metabolites not previously shown to be associated with CRI. These changes occurred in pathways reflecting protein degradation, oxidative stress, eicosanoid production, collagen matrix remodeling, mitochondrial stress, cell membrane composition and vascular disruption (107).…”

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

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Cutaneous Radiation Injuries: Models, Assessment and Treatments

et al. 2020

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Many cases of human exposures to high-dose radiation have been documented, including individuals exposed during the detonation of atomic bombs in Hiroshima and Nagasaki, nuclear power plant disasters (e.g., Chernobyl), as well as industrial and medical accidents. For many of these exposures, injuries to the skin have been present and have played a significant role in the progression of the injuries and survivability from the radiation exposure. There are also instances of radiation-induced skin complications in routine clinical radiotherapy and radiation diagnostic imaging procedures. In response to the threat of a radiological or nuclear mass casualty incident, the U.S. Department of Health and Human Services tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early-to mid-stage medical countermeasure (MCM) development to treat radiation-induced injuries, including those to the skin. To appropriately assess the severity of radiation-induced skin injuries and determine efficacy of different approaches to mitigate/treat them, it is necessary to develop animal models that appropriately simulate what is seen in humans who have been exposed. In addition, it is important to understand the techniques that are used in other clinical indications (e.g., thermal burns, diabetic ulcers, etc.) to accurately assess the extent of skin injury and progression of healing. For these reasons, the NIAID partnered with two other U.S. Government funding and regulatory agencies, the Biomedical Advanced Research and Development Authority (BARDA) and the Food and Drug Administration (FDA), to identify state-of-the-art methods in assessment of skin injuries, explore animal models to better understand radiation-induced cutaneous damage and investigate treatment approaches. A two-day workshop was convened in May 2019 highlighting talks from 28 subject matter experts across five scientific sessions. This report provides an overview of information that was presented and the subsequent guided discussions.

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Section: Session 2: Radiation Sources and Animal Models Of Cutaneous mentioning

confidence: 99%

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

Section: Session 5: Medical Countermeasures To Treat Crimentioning

confidence: 99%

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Cutaneous Radiation Injuries: Models, Assessment and Treatments

et al. 2020

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Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin

Satyamitra,

Andres,

Bergmann

et al. 2023

Disaster med. public health prep.

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Purpose: To summarize presentations and discussions from the 2022 trans-agency workshop titled “Overlapping Science in Radiation and Sulfur Mustard (SM) Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures.” Methods: Summary on topics includes: 1) an overview of the radiation and chemical countermeasure development programs and missions; 2) regulatory and industry perspectives for drugs and devices; 3) pathophysiology of skin and lung following radiation or SM exposure; 4) mechanisms of action/targets, biomarkers of injury; and 5) animal models that simulate anticipated clinical responses. Results: There are striking similarities between injuries caused by radiation and SM exposures. Primary outcomes from both types of exposure include acute injuries, while late complications comprise chronic inflammation, oxidative stress, and vascular dysfunction, which can culminate in fibrosis in both skin and lung organ systems. This workshop brought together academic and industrial researchers, medical practitioners, U.S. Government program officials and regulators to discuss lung-, and skin-specific animal models and biomarkers, novel pathways of injury and recovery, and paths to licensure for products to address radiation or SM injuries. Conclusions: Regular communications between the radiological and chemical injury research communities can enhance the state-of-the-science, provide a unique perspective on novel therapeutic strategies, and improve overall U.S. Government emergency preparedness.

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Radiation and Chemical Program Research for Multi-Utility and Repurposed Countermeasures: A US Department of Health and Human Services Agencies Perspective

Rios,

Garcia,

Hogdahl

et al. 2024

Disaster med. public health prep.

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Although chemical and radiological agents cause toxicity through different mechanisms, the multiorgan injuries caused by these threats share similarities that convene on the level of basic biological responses. This publication will discuss these areas of convergence and explore “multi-utility” approaches that could be leveraged to address common injury mechanisms underlying actions of chemical and radiological agents in a threat-agnostic manner. In addition, we will provide an overview of the current state of radiological and chemical threat research, discuss the US Government’s efforts toward medical preparedness, and identify potential areas for collaboration geared toward enhancing preparedness and response against radiological and chemical threats. We also will discuss previous regulatory experience to provide insight on how to navigate regulatory paths for US Food and Drug Administration (FDA) approval/licensure/clearance for products addressing chemical or radiological/nuclear threats. This publication follows a 2022 trans-agency meeting titled, “Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures,” sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Discussions from this meeting explored the overlapping nature of radiation and chemical injury and spurred increased interest in how preparedness for one threat leads to preparedness for the other. Herein, subject matter experts from the NIAID and the Biomedical Advanced Research and Development Authority (BARDA), a part of the Administration for Strategic Preparedness and Response (ASPR), summarize the knowledge gained from recently funded biomedical research, as well as insights from the 2022 meeting. These topics include identification of common areas for collaboration, potential use of biomarkers of injury to identify injuries caused by both hazards, and common and widely available treatments that could treat damage caused by radiological or chemical threats.

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Biomolecular Analysis of Beta Dose-Dependent Cutaneous Radiation Injury in a Porcine Model

Cited by 8 publications

References 48 publications

Cutaneous Radiation Injuries: Models, Assessment and Treatments

Cutaneous Radiation Injuries: Models, Assessment and Treatments

Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin

Radiation and Chemical Program Research for Multi-Utility and Repurposed Countermeasures: A US Department of Health and Human Services Agencies Perspective

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