RESUMEN
Hematopoietic growth factors (HGF) are recommended therapy for high dose radiation exposure, but unfavorable administration schedules requiring early and repeat dosing limit the logistical ease with which they can be used. In this report, using a previously described murine model of H-ARS, survival efficacy and effect on hematopoietic recovery of unique PEGylated HGF were investigated. The PEGylated-HGFs possess longer half-lives and more potent hematopoietic properties than corresponding non-PEGylated-HGFs. C57BL/6 mice underwent single dose lethal irradiation (7.76-8.72 Gy, Cs, 0.62-1.02 Gy min) and were treated with various dosing regimens of 0.1, 0.3, and 1.0 mg kg of analogs of human PEG-G-CSF, murine PEG-GM-CSF, or human PEG-IL-11. Mice were administered one of the HGF analogs at 24-28 h post irradiation, and in some studies, additional doses given every other day (beginning with the 24-28 h dose) for a total of three or nine doses. Thirty-day (30 d) survival was significantly increased with only one dose of 0.3 mg kg of PEG-G-CSF and PEG-IL-11 or three doses of 0.3 mg kg of PEG-GM-CSF (p ≤ 0.006). Enhanced survival correlated with consistently and significantly enhanced WBC, NE, RBC, and PLT recovery for PEG-G- and PEG-GM-CSF, and enhanced RBC and PLT recovery for PEG-IL-11 (p ≤ 0.05). Longer administration schedules or higher doses did not provide a significant additional survival benefit over the shorter, lower dose, schedules. These data demonstrate the efficacy of BBT's PEG-HGF to provide significantly increased survival with fewer injections and lower drug doses, which may have significant economic and logistical value in the aftermath of a radiation event.
Asunto(s)
Síndrome de Radiación Aguda/tratamiento farmacológico , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Hematopoyesis/efectos de los fármacos , Interleucina-11/farmacología , Polietilenglicoles/química , Síndrome de Radiación Aguda/fisiopatología , Animales , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/química , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/química , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Hematopoyesis/efectos de la radiación , Humanos , Interleucina-11/administración & dosificación , Interleucina-11/química , Interleucina-11/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico , Análisis de Supervivencia , Adulto JovenRESUMEN
PURPOSE: Previous studies have reported higher dental fluorosis prevalence in high-altitude communities than in low-altitude communities. This investigation determined and compared dental fluorosis prevalence in populations of children living at high and low altitudes in Mexico. MATERIALS AND METHODS: Fluorosis prevalence was determined in 7 to 10-year-old children: 67 in Mexico City (2,240 m) and 71 in Veracruz (sea level). Previous fluoride exposure of those children was surveyed by retrospective, questionnaire data. The fluoride content of water and salt from those communities was also documented. RESULTS: Fluorosis prevalence in Mexico City (53.0%) was significantly higher than in Veracruz (24.3%) (p < 0.0001). While there were statistical differences in one of the fluorosis risk factors between the two communities, the observed difference in fluorosis prevalence was still significant when data were analyzed after adjusting for the reported differences in that factor. CONCLUSION: Our results led to the conclusion that the difference in fluorosis prevalence in Mexico City and Veracruz could not be explained by differences in fluoride content of the salt or water samples, self-reported exposure to fluorosis risk factors or estimated fluoride intake.