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Anti-ceramide Single-Chain Variable Fragment Mitigates Gastrointestinal-AcuteRadiationSyndrome and Improves Marrow Reconstitution, Rendering Near-Normal 90-Day Autopsies. After September 11, 2001, nuclear threat prompted government agencies to develop medical countermeasures to mitigate two syndromes, the hematopoietic-acuteradiationsyndrome (H-ARS) and the higher-dose gastrointestinal-acuteradiationsyndrome (GI-ARS), both lethal within weeks. While repurposing leukemia drugs that enhance bone marrow repopulation successfully treats H-ARS, no mitigator potentially deliverable under mass casualty conditions preserves the GI tract. We recently reported that anti-ceramide single-chain variable fragment (scFv) mitigates GI-ARS lethality, abrogating ongoing small intestinal endothelial apoptosis
A first-in-human study of KMRC011, a potential treatment for acuteradiationsyndrome, to explore tolerability, pharmacokinetics, and pharmacodynamics. KMRC011 is a novel Toll-like receptor 5 agonist under development as a treatment for acuteradiationsyndrome (ARS). The aim of this first-in-human study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of a single
Rescue from lethal acuteradiationsyndrome (ARS) with severe weight loss by secretome of intramuscularly injected human placental stromal cells. Most current cell-based regenerative therapies are based on the indirect induction of the affected tissues repair. Xenogeneic cell-based treatment with expanded human placenta stromal cells, predominantly from fetal origin (PLX-RAD cells), were shown to mitigate significantly acuteradiationsyndrome (ARS) following high dose irradiation in mice, with expedited regain of weight loss and haematopoietic function. The current mechanistic study explores the indirect effect of the secretome of PLX-RAD cells in the rescue of the irradiated mice. The mitigation of the ARS was investigated following two intramuscularly (IM) injected 2 × 10 PLX-RAD cells, 1
MicroRNA Expression for Early Prediction of Late Occurring Hematologic AcuteRadiationSyndrome in Baboons. For effective medical management of radiation-exposed persons after a radiological/nuclear event, blood-based screening measures in the first few days that could predict hematologic acuteradiationsyndrome (HARS) are needed. For HARS severity prediction, we used microRNA (miRNA) expression
AIMP3 Deletion Induces AcuteRadiationSyndrome-like Phenotype in Mice Genomes are mostly protected from constant DNA-damaging threats, either internal or external, which ultimately sustain the organism. Herein, we report that AIMP3, a previously demonstrated tumour suppressor, plays an essential role in maintaining genome integrity in adult mice. Upon induction of the temporal systemic deletion of AIMP3 by tamoxifen in adult mice, the animals developed an acuteradiationsyndrome-like phenotype, typified by scleroderma, hypotrophy of haematopoietic cells and organs, and intestinal failure. Induction of γH2AX, an early marker of DNA double-strand breaks, was observed in the spleen, intestine, and the highly replicating embryonic cortex. In addition, sub-lethal irradiation of AIMP3 mKO mice
Acuteradiationsyndrome in a non-destructive testing worker: a case report In Korea, there were repeated radiation exposure accidents among non-destructive testing workers. Most of the cases involved local injury, such as radiation burns or hematopoietic cancer. Herein, we report a case of acuteradiationsyndrome caused by short periods of high exposure to ionizing radiation. In January 2017 pancytopenia and the patient was diagnosed with acuteradiationsyndrome (white blood cells: 1400/cubic mm, hemoglobin: 7.1 g/dL, platelets: 14000/cubic mm). He was immediately prohibited from working and blood transfusion was commenced. The patient's radiation exposure dose was over 1.4 Gy (95% confidence limits: 1.1-1.6) in lymphocyte depletion kinetics. It was revealed that the patient had been performing
Medical management of acuteradiationsyndrome and associated infections in a high-casualty incident A high-casualty incident may result in a significant human toll due to the inability of a community to meet the health care demands of the population. A successful medical response requires health care facilities to not only communicate and integrate medical services, meet surge capacity, protect of each of the four sub-syndromes that compose acuteradiationsyndrome (ARS), including the hematopoietic subsyndrome (HS), gastrointestinal subsyndrome (GIS), neurovascular subsyndrome (NVS) and cutaneous subsyndrome (CS). Major findings in studies meeting inclusion criteria for management strategies for HS were that (i) no randomized controlled studies of medical countermeasures have been
The Toll–Like Receptor 2/6 Agonist, FSL–1 Lipopeptide, Therapeutically Mitigates AcuteRadiationSyndrome Risks of radiation exposure from nuclear incidents and cancer radiotherapy are undeniable realities. These dangers urgently compel the development of agents for ameliorating radiation-induced injuries. Biologic pathways mediated by myeloid differentiation primary response gene 88 (MyD88
Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates AcuteRadiationSyndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma Exposure to ionizing radiation alone or combined with traumatic tissue injury is a crucial life-threatening factor in nuclear and radiological incidents. Radiation injuries occur at the molecular, cellular, tissue (a cytokine for neutrophil maturation and mobilization) and Alxn4100TPO (a thrombopoietin receptor agonist) at 4 h postirradiation, a 95% survival (vehicle: 60%) over the 30-day period, along with mitigated body-weight loss and significantly reduced acuteradiationsyndrome. In animals that received combined treatment of radiation and injury that received pegylated G-CSF and Alxn4100TPO, survival
Citrulline as a Biomarker for Gastrointestinal-AcuteRadiationSyndrome: Species Differences and Experimental Condition Effects Animal models of hematopoietic and gastrointestinal acuteradiationsyndromes (ARS) have been characterized to develop medical countermeasures. Acute radiation-induced decrease of intestinal absorptive function has been correlated to a decrease in the number
Mesenchymal stem cell therapy for acuteradiationsyndromeAcuteradiationsyndrome affects military personnel and civilians following the uncontrolled dispersal of radiation, such as that caused by detonation of nuclear devices and inappropriate medical treatments. Therefore, there is a growing need for medical interventions that facilitate the improved recovery of victims and patients. One promising approach may be cell therapy, which, when appropriately implemented, may facilitate recovery from whole body injuries. This editorial highlights the current knowledge regarding the use of mesenchymal stem cells for the treatment of acuteradiationsyndrome, the benefits and limitations of which are under investigation. Establishing successful therapies for acuteradiationsyndrome may require
γ-Tocotrienol as a Promising Countermeasure for AcuteRadiationSyndrome: Current Status The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acuteradiationsyndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its
Gastrointestinal AcuteRadiationSyndrome in Göttingen Minipigs (Sus Scrofa Domestica) In the absence of supportive care, exposing Göttingen minipigs to γ-radiation doses of less than 2 Gy achieves lethality due to hematopoietic acuteradiationsyndrome. Doses of 2 to 5 Gy are associated with an accelerated hematopoietic syndrome, characterized by villus blunting and fusion, the beginning of sepsis, and a mild transient reduction in plasma citrulline concentration. We exposed male Göttingen minipigs (age, 5 mo; weight, 9 to 11 kg) to γ-radiation doses of 5 to 12 Gy (total body; (60)Co, 0.6 Gy/min) to test whether these animals exhibit classic gastrointestinal acuteradiationsyndrome (GI-ARS). After exposure, the minipigs were monitored for 10 d by using clinical signs, CBC counts
Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acuteradiationsyndrome The radioprotective effect of hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 - dose that kills 100 % of the mice at 30 days) from Cs with a dose of 2.05 Gy/min. Radiation injuries were manifested by inducing а hematopoietic form of acuteradiationsyndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2
A nonhuman primate model of the hematopoietic acuteradiationsyndrome plus medical management. The development of medical countermeasures against the hematopoietic subsyndrome of the acuteradiationsyndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include of the hematopoietic acuteradiationsyndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.
MRI assessment of local acuteradiationsyndrome. To describe local acuteradiationsyndrome and its radiological imaging characteristics. We performed a retrospective study of patients who had suffered skin and deeper radiation damage who were investigated by magnetic resonance imaging (MRI). We compared the clinical findings, C-reactive protein (CRP) levels and MRI results. A total of 22 MRI with clinical stage and no false negative examinations were obtained. In particular, the association between normal MRI and low CRP level seems to be related to good outcome without specific treatment. Local acuteradiationsyndrome (radioepidermitis) mainly affects the skin and superficial tissues. MRI findings correspond with clinical stage (with a strong negative predictive value). MRI outperformed X-ray
for Antiemetic Research. Radiation-induced emesis: a prospective observational multicenter Italian trial (1999) The Italian Group for Antiemetic Research in Radiotherapy. Int J Radiat Oncol Biol Phys 44(3):619–625. https://doi.org/10.1016/s0360-3016(99)00055-3Article Google Scholar Danjoux CE, Rider WD, Fitzpatrick PJ (1979) Acuteradiationsyndrome - memorial to courtbrown, William, Michael. Clin Radiol 30(5
Open-label Phase I Study for PEP or Treatment of HS-ARS PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of AcuteRadiationSyndrome (HS-ARS) The objective of the study is to evaluate the safety of intramuscular (IM) administration of PLX-R18 in subjects exposed to ionizing radiation and who are at risk of developing HS-ARS.Indication:Post-Exposure Prevention (PEP) or treatment of Hematopoietic Syndrome of AcuteRadiationSyndrome (HS-ARS) in subjects suspected to have been exposed to ionizing radiation. This will be a Phase I, open-label safety study; each subject will receive two administrations of PLX-R18, 4 days apart. Each administration of PLX-R18 will contain 4 million cells/kg (up to a maximal dose of 400 million cells). The first administration