title: Non-human Primate Total-body Irradiation Model with Limited and Full Medical Supportive Care Including Filgrastim for Biodosimetry and Injury Assessment.
abstract: An assessment of multiple biomarkers from radiation casualties undergoing limited- or full-supportive care including treatment with filgrastim is critical to develop rapid and effective diagnostic triage strategies. The efficacy of filgrastim with full-supportive care was compared with results with limited-supportive care by analyzing survival, necropsy, histopathology and serial blood samples for hematological, serum chemistry and protein profiles in a non-human primate (Macaca mulatta, male and female) model during 60-d post-monitoring period following sham- and total-body irradiation with 6.5 Gy60Co gamma-rays at 0.6 Gy min-1Filgrastim (10 μg kg-1) was administered beginning on Day 1 post-exposure and continued daily until neutrophil counts were ≥2,000 μL-1for two consecutive days. Filgrastim and full-supportive care significantly decreased the pancytopenia duration and resulted in improved animal survival and recovery compared to animals with a limited-supportive care. These findings also identified and validated a multiparametric biomarker panel to support radiation diagnostic device development.
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA Natalia.Ossetrova@usuhs.edu.
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Ossetrova
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Blakely
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Nagy
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.
authors.forename: Camille
authors.initials: C
authors.lastname: McGann
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Ney
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.|Tri-Service Research Laboratory (TRSL), 4141 Petroleum Road, JBSA-Fort Sam Houston, TX 78234, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Christensen
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.|Tripler Army Medical Center, Honolulu, HI 96859, USA.
authors.forename: Amory L
authors.initials: AL
authors.lastname: Koch
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Gulani
authors.affiliation: Meso Scale Diagnostics, LLC. (MSD), 1601 Research Boulevard, Rockville, MD 20850, USA.
authors.forename: George B
authors.initials: GB
authors.lastname: Sigal
authors.affiliation: Meso Scale Diagnostics, LLC. (MSD), 1601 Research Boulevard, Rockville, MD 20850, USA.
authors.forename: Eli N
authors.initials: EN
authors.lastname: Glezer
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University (USU) , 8901 Wisconsin Avenue, Bethesda, ML 20889, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Hieber
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D000069585:Filgrastim / Q000627:therapeutic use*; D008253:Macaca mulatta; D008297:Male; D011829:Radiation Dosage; D000069079:Radiation Exposure / Q000032:analysis; D011832:Radiation Injuries / Q000097:blood / Q000175:diagnosis* / Q000628:therapy*; D011834:Radiation Monitoring / Q000379:methods*; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D015415:Biomarkers; D011837:Radiation-Protective Agents; D000069585:Filgrastim