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24 results on '"Gasperetti, Tracy"'

2. IEPA, a novel radiation countermeasure, alleviates acute radiation syndrome in rodents.

Author

Wesolowski, Radoslaw, Fish, Brian L., Eibl, Michael, Bähr, Stella, Munjal Mehta, Srishti, Czajkowski, Maciej T., Gasperetti, Tracy, Orschell, Christie M., Asang, Corinna, Singh, Nikita, Himburg, Heather A., and Pleimes, Dirk

Subjects
LABORATORY rats, RADIATION injuries, RADIATION exposure, LABORATORY mice, FILGRASTIM
Abstract

Repurposing therapeutic agents with existing clinical data is a common strategy for developing radiation countermeasures. IEPA (imidazolyl ethanamide pentandioic acid) is an orally bioavailable small molecule pseudopeptide with myeloprotective properties, a good clinical safety profile, and stable chemical characteristics facilitating stockpiling. Here, we evaluated IEPA's radiomitigative efficacy in the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) using total-body irradiation (TBI) models in C57BL/6J mice and WAG/RijCmcr rats, applying various posology schemes and introducing syringe feeding of the IEPA formulation in the pudding. Additionally, we assessed IEPA in the delayed effects of acute radiation exposure (DEARE) model after partial-body irradiation (PBI) in WAG/RijCmcr rats. Endpoints included survival, body weight, hematology, and pulmonary parameters, depending on the model. Results from mouse and rat TBI models demonstrated survival improvements with repeated IEPA dosing at 10 mg/kg, with the largest benefits observed in the bi-daily (BID) treatment over the 30-day ARS phase in female rats. Survival across PBI-DEARE subsyndromes was comparable between IEPA and vehicle groups, though IEPA improved pulmonary parameters in female rats during the lung-DEARE phase. Sex-related differences in response to irradiation and IEPA were noted, with females showing a survival advantage. IEPA treatment is compatible with Neulasta® (Pegfilgrastim; PEG-G-CSF); adequately powered studies are needed to confirm the trend toward improved survival over standard care alone. IEPA is a promising development candidate as a medical countermeasure against the effects of acute radiation syndrome. Further confirmatory studies in small and large animal models should validate the robustness and translatability of preliminary rodent data on IEPA's radiomitigative efficacy. [ABSTRACT FROM AUTHOR]

Published
2025
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3. 2nd Window NIR Imaging of Radiation Injury Mitigation Provided by Reduced Notch-Dll4 Expression on Vasculature

Author

Kondelaji, Mir Hadi Razeghi, primary, Sharma, Guru Prasad, additional, Jagtap, Jaidip, additional, Shafiee, Shayan, additional, Hansen, Christopher, additional, Gasperetti, Tracy, additional, Frei, Anne, additional, Veley, Dana, additional, Narayanan, Jayashree, additional, Fish, Brian L., additional, Parchur, Abdul K., additional, Ibrahim, El-Sayed H., additional, Medhora, Meetha, additional, Himburg, Heather A., additional, and Joshi, Amit, additional

Published
2023
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6. 2nd Window NIR Imaging of Radiation Injury Mitigation Provided by Reduced Notch-Dll4 Expression on Vasculature.

Author

Kondelaji, Mir Hadi Razeghi, Sharma, Guru Prasad, Jagtap, Jaidip, Shafiee, Shayan, Hansen, Christopher, Gasperetti, Tracy, Frei, Anne, Veley, Dana, Narayanan, Jayashree, Fish, Brian L., Parchur, Abdul K., Ibrahim, El-Sayed H., Medhora, Meetha, Himburg, Heather A., and Joshi, Amit

Subjects
RADIATION injuries, ENDOTHELIUM, ENDOTHELIAL cells, VASCULAR endothelial cells, VASCULAR endothelium, INDOCYANINE green, BLOOD vessels
Abstract

Purpose: Vascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100 nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney. Procedures: Consomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11–12 weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13 Gy partial body irradiation at 42- and 90 days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection. Results: We show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction. Conclusions: Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Differences in radiation-induced heart dysfunction in male versus female rats

Author

Andruska, Neal, primary, Schlaak, Rachel A., additional, Frei, Anne, additional, Schottstaedt, Aronne M., additional, Lin, Chieh-Yu, additional, Fish, Brian L., additional, Gasperetti, Tracy, additional, Mpoy, Cedric, additional, Pipke, Jamie L., additional, Pedersen, Lauren N., additional, Flister, Michael J., additional, Javaheri, Ali, additional, and Bergom, Carmen, additional

Published
2023
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14. Lisinopril Mitigates Radiation-Induced Mitochondrial Defects in Rat Heart and Blood Cells

Author

Ortiz de Choudens, Saryleine, primary, Sparapani, Rodney, additional, Narayanan, Jayashree, additional, Lohr, Nicole, additional, Gao, Feng, additional, Fish, Brian L., additional, Zielonka, Monika, additional, Gasperetti, Tracy, additional, Veley, Dana, additional, Beyer, Andreas, additional, Olson, Jessica, additional, Jacobs, Elizabeth R., additional, and Medhora, Meetha, additional

Published
2022
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16. Rat Models of Partial-body Irradiation with Bone Marrow-sparing (Leg-out PBI) Designed for FDA Approval of Countermeasures for Mitigation of Acute and Delayed Injuries by Radiation

Author

Fish, Brian L., primary, MacVittie, Thomas J., additional, Gao, Feng, additional, Narayanan, Jayashree, additional, Gasperetti, Tracy, additional, Scholler, Dana, additional, Sheinin, Yuri, additional, Himburg, Heather A., additional, Hart, Barry, additional, and Medhora, Meetha, additional

Published
2021
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18. Polypharmacy to Mitigate Acute and Delayed Radiation Syndromes

Author

Gasperetti, Tracy, primary, Miller, Tessa, additional, Gao, Feng, additional, Narayanan, Jayashree, additional, Jacobs, Elizabeth R., additional, Szabo, Aniko, additional, Cox, George N., additional, Orschell, Christie M., additional, Fish, Brian L., additional, and Medhora, Meetha, additional

Published
2021
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22. Mapping genetic modifiers of radiation-induced cardiotoxicity to rat chromosome 3

Author

Schlaak, Rachel A., primary, Frei, Anne, additional, Schottstaedt, Aronne M., additional, Tsaih, Shirng-Wern, additional, Fish, Brian L., additional, Harmann, Leanne, additional, Liu, Qian, additional, Gasperetti, Tracy, additional, Medhora, Meetha, additional, North, Paula E., additional, Strande, Jennifer L., additional, Sun, Yunguang, additional, Rui, Hallgeir, additional, Flister, Michael J., additional, and Bergom, Carmen, additional

Published
2019
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