RESUMO
Radiation-induced pulmonary fibrosis (RTPF) is a progressive, serious condition in many subjects treated for thoracic malignancies or after accidental nuclear exposure. No biomarker exists for identifying the irradiated subjects most susceptible to pulmonary fibrosis (PF). Previously, we determined that gastrin-releasing peptide (GRP) was elevated within days after birth in newborns exposed to hyperoxia who later developed chronic lung disease. The goal of the current study was to test whether radiation (RT) exposure triggers GRP release in mice and whether this contributes to RTPF in vivo. We determined urine GRP levels and lung GRP immunostaining in mice 0 to 24 after post-thoracic RT (15 Gy). Urine GRP levels were significantly elevated between 24 hours post-RT; GRP-blocking monoclonal antibody 2A11, given minutes post-RT, abrogated urine GRP levels by 6 to 12 hours and also altered phosphoprotein signaling pathways at 24 hours post-RT. Strong extracellular GRP immunostaining was observed in lung at 6 hours post-RT. Mice given one dose of GRP monoclonal antibody 2A11 24 hours post-RT had significantly reduced myofibroblast accumulation and collagen deposition 15 weeks later, indicating protection against lung fibrosis. Therefore, elevation of urine GRP could be predictive of RTPF development. In addition, transient GRP blockade could mitigate PF in normal lung after therapeutic or accidental RT exposure.
Assuntos
Raios gama/efeitos adversos , Peptídeo Liberador de Gastrina/metabolismo , Fosfoproteínas/metabolismo , Fibrose Pulmonar/etiologia , Lesões por Radiação/etiologia , Animais , Feminino , Camundongos , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Lesões por Radiação/metabolismo , Lesões por Radiação/patologiaRESUMO
This is a case of a 36-year-old Spanish-speaking Hispanic man who was brought to a busy suburban New Jersey emergency department (ED) by family members for altered mental status. By report, patient was noted by family to be "not acting normal" at home, when he went into his bathroom and locked the door. A brief time thereafter, he emerged smelling of bleach and with confused speech. The family surmised that he tried to commit suicide by drinking bleach and emergently brought the patient to the ED.