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https://www.readbyqxmd.com/read/28650707/a-review-of-radiation-countermeasures-focusing-on-injury-specific-medicinals-and-regulatory-approval-status-part-i-radiation-sub-syndromes-animal-models-and-fda-approved-countermeasures
#1
Vijay K Singh, Thomas M Seed
PURPOSE: The increasing global risk of nuclear and radiological accidents or attacks has driven renewed research interest in developing medical countermeasures to potentially injurious exposures to acute irradiation. Clinical symptoms and signs of a developing acute radiation injury, i.e. the acute radiation syndrome, are grouped into three sub-syndromes named after the dominant organ system affected, namely the hematopoietic, gastrointestinal, and neurovascular systems. The availability of safe and effective countermeasures against the above threats currently represents a significant unmet medical need...
June 26, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28649630/towards-human-exploration-of-space-the-theseus-review-series-on-muscle-and-bone-research-priorities
#2
Thomas Lang, Jack J W A Van Loon, Susan Bloomfield, Laurence Vico, Angele Chopard, Joern Rittweger, Antonios Kyparos, Dieter Blottner, Ilkka Vuori, Rupert Gerzer, Peter R Cavanagh
Without effective countermeasures, the musculoskeletal system is altered by the microgravity environment of long-duration spaceflight, resulting in atrophy of bone and muscle tissue, as well as in deficits in the function of cartilage, tendons, and vertebral disks. While inflight countermeasures implemented on the International Space Station have evidenced reduction of bone and muscle loss on low-Earth orbit missions of several months in length, important knowledge gaps must be addressed in order to develop effective strategies for managing human musculoskeletal health on exploration class missions well beyond Earth orbit...
2017: NPJ Microgravity
https://www.readbyqxmd.com/read/28641684/novel-indications-for-commonly-used-medications-as-radiation-protectants-in-spaceflight
#3
Mark F McLaughlin, Dorit B Donoviel, Jeffrey A Jones
In the space environment, the traditional radioprotective principles of time, distance, and shielding become difficult to implement. Additionally, the complex radiation environment inherent in space, the chronic exposure timeframe, and the presence of numerous confounding variables complicate the process of creating appropriate risk models for astronaut exposure. Pharmaceutical options hold tremendous promise to attenuate acute and late effects of radiation exposure in the astronaut population. Pharmaceuticals currently approved for other indications may also offer radiation protection, modulation, or mitigation properties along with a well-established safety profile...
July 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28605260/cellular-therapies-for-treatment-of-radiation-injury-report-from-a-nih-niaid-and-irsn-workshop
#4
Andrea L DiCarlo, Radia Tamarat, Carmen I Rios, Marc Benderitter, Christine W Czarniecki, Theresa C Allio, Francesca Macchiarini, Bert W Maidment, Jean-Rene Jourdain
In recent years, there has been increasing concern over the possibility of a radiological or nuclear incident occurring somewhere in the world. Intelligence agencies frequently report that terrorist groups and rogue nations are seeking to obtain radiological or nuclear weapons of mass destruction. In addition, there exists the real possibility that safety of nuclear power reactors could be compromised by natural (such as the tsunami and subsequent Fukushima accident in Japan in March, 2011) or accidental (Three Mile Island, 1979 and Chernobyl, 1986) events...
June 12, 2017: Radiation Research
https://www.readbyqxmd.com/read/28561779/transcriptomics-nf-%C3%AE%C2%BAb-pathway-and-their-potential-spaceflight-related-health-consequences
#5
REVIEW
Ye Zhang, Maria Moreno-Villanueva, Stephanie Krieger, Govindarajan T Ramesh, Srujana Neelam, Honglu Wu
In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions...
May 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28545017/12-o-tetradecanoylphorbol-13-acetate-tpa-increases-murine-intestinal-crypt-stem-cell-survival-following-radiation-injury
#6
Yaojie Liang, Hongwei Zhou, Yibing Yao, Ailing Deng, Zhihong Wang, Boning Gao, Minhang Zhou, Yu Cui, Lili Wang, Lei Zhou, Bianhong Wang, Li Wang, Anqi Liu, Lanlan Qiu, Kun Qian, Yejian Lu, Wanping Deng, Xi Zheng, Zhengtao Han, Yonghui Li, Junzhong Sun
Radiation enteropathy is a common complication in cancer patients following radiation therapy. Thus, there is a need for agents that can protect the intestinal epithelium against radiation. 12-O-Tetradecanoylphorbol-13-acetate (TPA) has been shown to induce differentiation and/or apoptosis in multiple cell lines and primary cells. In the current report, we studied the function of TPA in radiation induced enteropathy in cultured rat intestinal epithelial cell line IEC-6 after ionizing radiation (IR) and in mice after high dose total-body gamma-IR (TBI)...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534834/combining-pharmacological-countermeasures-to-attenuate-the-acute-radiation-syndrome-a-concise-review
#7
REVIEW
Michal Hofer, Zuzana Hoferová, Daniel Depeš, Martin Falk
The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations...
May 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28441902/nonhuman-primates-as-models-for-the-discovery-and-development-of-radiation-countermeasures
#8
Vijay K Singh, Ayodele O Olabisi
Despite significant scientific advances over the past six decades toward the development of safe and effective radiation countermeasures for humans using animal models, only two pharmaceutical agents have been approved by United States Food and Drug Administration (US FDA) for hematopoietic acute radiation syndrome (H-ARS). Additional research efforts are needed to further develop large animal models for improving the prediction of clinical safety and effectiveness of radiation countermeasures for ARS and delayed effects of acute radiation exposure (DEARE) in humans...
May 5, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28437188/further-characterization-of-the-mitigation-of-radiation-lethality-by-protective-wounding
#9
Joseph R Dynlacht, Joy Garrett, Rebecca Joel, Katharina Lane, Marc S Mendonca, Christie M Orschell
There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%...
June 2017: Radiation Research
https://www.readbyqxmd.com/read/28435051/akt1-nf%C3%AE%C2%BAb-signaling-pathway-activation-by-a-small-molecule-dma-confers-radioprotection-to-intestinal-epithelium-in-xenograft-model
#10
Vinod Tiwari, Mohammad Zahid Kamran, Atul Ranjan, Hemlata Nimesh, Manish Singh, Vibha Tandon
Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28388223/public-understanding-of-medical-countermeasures
#11
Brooke Fisher Liu, Sandra C Quinn, Michael Egnoto, Vicki Freimuth, Natalie Boonchaisri
Medical countermeasures, including new drugs and vaccines, are necessary to protect the public's health from novel diseases and terrorist threats. Experience with the 2001 anthrax attack and the 2009 H1N1 pandemic suggest that there is limited willingness to accept such drugs and that minority groups may respond differently from others. We conducted 148 intercept interviews in the metropolitan Washington, DC, area, examining 2 hypothetical scenarios: a new respiratory virus and public exposure to high levels of radiation...
March 2017: Health Security
https://www.readbyqxmd.com/read/28362168/impact-of-abbreviated-filgrastim-schedule-on-survival-and-hematopoietic-recovery-after-irradiation-in-four-mouse-strains-with-different-radiosensitivity
#12
Merriline Satyamitra, Vidya P Kumar, Shukla Biswas, Lynnette Cary, Leonora Dickson, Srinivasan Venkataraman, Sanchita P Ghosh
Filgrastim (Neupogen(®), granulocyte-colony stimulating factor) is among the few countermeasures recommended for management of patients in the event of lethal total-body irradiation. Despite the plethora of studies using filgrastim as a radiation countermeasure, relatively little is known about the optimal dose schedule of filgrastim to mitigate radiation lethality. We evaluated the efficacy of filgrastim in improving 30-day survival of CD2F1 mice irradiated with a lethal dose (LD70/30) in the AFRRI cobalt-60 facility...
June 2017: Radiation Research
https://www.readbyqxmd.com/read/28350824/time-and-radiation-dose-dependent-changes-in-the-plasma-proteome-after-total-body-irradiation-of-non-human-primates-implications-for-biomarker-selection
#13
Stephanie D Byrum, Marie S Burdine, Lisa Orr, Samuel G Mackintosh, Simon Authier, Mylene Pouliot, Martin Hauer-Jensen, Alan J Tackett
Acute radiation syndrome (ARS) is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI) in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6...
2017: PloS One
https://www.readbyqxmd.com/read/28331119/estimation-of-biological-effects-of-tritium
#14
Toshiyuki Umata
Nuclear fusion technology is expected to create new energy in the future. However, nuclear fusion requires a large amount of tritium as a fuel, leading to concern about the exposure of radiation workers to tritium beta radiation. Furthermore, countermeasures for tritium-polluted water produced in decommissioning of the reactor at Fukushima Daiichi Nuclear Power Station may potentially cause health problems in radiation workers. Although, internal exposure to tritium at a low dose/low dose rate can be assumed, biological effect of tritium exposure is not negligible, because tritiated water (HTO) intake to the body via the mouth/inhalation/skin would lead to homogeneous distribution throughout the whole body...
2017: Journal of UOEH
https://www.readbyqxmd.com/read/28289414/podophyllotoxin-and-rutin-modulates-ionizing-radiation-induced-oxidative-stress-and-apoptotic-cell-death-in-mice-bone-marrow-and-spleen
#15
Abhinav Singh, M H Yashavarddhan, Bhargab Kalita, Rajiv Ranjan, Sania Bajaj, Hridayesh Prakash, Manju Lata Gupta
The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (-1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28251902/evolutionarily-conserved-serum-micrornas-predict-radiation-induced-fatality-in-nonhuman-primates
#16
Wojciech Fendler, Beata Malachowska, Khyati Meghani, Panagiotis A Konstantinopoulos, Chandan Guha, Vijay K Singh, Dipanjan Chowdhury
Effective planning for the medical response to a radiological or nuclear accident is complex. Because of limited resources for medical countermeasures, the key would be to accurately triage and identify victims most likely to benefit from treatment. We used a mouse model system to provide evidence that serum microRNAs (miRNAs) may effectively predict the impact of radiation on the long-term viability of animals. We had previously used nonhuman primates (NHPs) to demonstrate that this concept is conserved and serum miRNA signatures have the potential to serve as prediction biomarkers for radiation-induced fatality in a human population...
March 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28208025/aeol-10150-mitigates-radiation-induced-lung-injury-in-the-nonhuman-primate-morbidity-and-mortality-are-administration-schedule-dependent
#17
Thomas J MacVittie, Allison Gibbs, Ann M Farese, Kory Barrow, Alexander Bennett, Cheryl Taylor-Howell, Abdul Kazi, Karl Prado, George Parker, William Jackson Iii
Pneumonitis and fibrosis are potentially lethal, delayed effects of acute radiation exposure. In this study, male rhesus macaques received whole-thorax lung irradiation (WTLI) with a target dose of 10.74 Gy prescribed to midplane at a dose rate of 0.80 ± 0.05 Gy/min using 6 MV linear accelerator-derived photons. The study design was comprised of four animal cohorts: one control and three treated with AEOL 10150 (n = 20 animals per cohort). AEOL 10150, a metalloporphyrin antioxidant, superoxide dismutase mimetic was administered by daily subcutaneous injection at 5 mg/kg in each of three schedules, beginning 24 ± 2 h postirradiation: from day 1 to day 28, day 1 to day 60 or a divided regimen from day 1 to day 28 plus day 60 to day 88...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28163296/decontamination-reduces-radiation-anxiety-and-improves-subjective-well-being-after-the-fukushima-accident
#18
Michio Murakami, Shigeki Harada, Taikan Oki
Since the 2011 Fukushima accident, rebuilding society to protect against anxiety and improve feelings of well-being has grown in importance. A questionnaire was carried out among residents of Marumori Town, Igu County, Miyagi Prefecture, to evaluate the effects of radiation-related countermeasures implemented by the town to reduce residents' anxiety and improve their subjective well-being (response rate: 31%; valid responses: n = 174). Further, to propose effective countermeasures regarding town planning for the improvement in subjective well-being, we analyzed associations between residents' sense of attachment to the town and subjective well-being, and then identified primary factors behind their sense of attachment...
February 2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28145432/succinate-ester-derivative-of-%C3%AE-tocopherol-enhances-the-protective-effects-against-60-co-%C3%AE-ray-induced-hematopoietic-injury-through-granulocyte-colony-stimulating-factor-induction-in-mice
#19
Zhong-Tang Li, Li-Mei Wang, Li-Rong Yi, Chao Jia, Fan Bai, Ren-Jun Peng, Zu-Yin Yu, Guo-Lin Xiong, Shuang Xing, Ya-Jun Shan, Ri-Fang Yang, Jun-Xing Dong, Yu-Wen Cong
α-tocopherol succinate (α-TOS), γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have drawn large attention due to their efficacy as radioprotective agents. α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI). Because α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI), we hypothesized succinate may be contribute to the radioprotection of α-TOS. To study the contributions of succinate and to identify stronger radioprotective agents, we synthesized α-, γ- and δ-TOS...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28118115/multivariate-analysis-of-radiation-responsive-proteins-to-predict-radiation-exposure-in-total-body-irradiation-and-partial-body-irradiation-models
#20
Mary Sproull, Tamalee Kramp, Anita Tandle, Uma Shankavaram, Kevin Camphausen
In the event of a radiological or nuclear attack, advanced clinical countermeasures are needed for screening and medical management of the exposed population. In such a scenario, minimally invasive biomarkers that can accurately quantify radiation exposure would be useful for triage management by first responders. In this murine study, we evaluated the efficacy of a novel combination of radiation responsive proteins, Flt3 ligand (FL), serum amyloid A (SAA), matrix metalloproteinase 9 (MMP9), fibrinogen beta (FGB) and pentraxin 3 (PTX3) to predict the received dose after whole- or partial-body irradiation...
February 2017: Radiation Research
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