Interaction between maternal and offspring diet to impair vascular function and oxidative balance in high fat fed male mice

Aims: to determine the impact of maternal and post-weaning consumption of a high fat diet on endothelium-dependent vasorelaxation and redox regulation in adult male mouse offspring.Methods: female C57BL6J mice were fed an obesogenic high fat diet (HF, 45% kcal fat) or standard chow (C, 21% kcal fat) pre-conception and throughout pregnancy and lactation. Post-weaning, male offspring were continued on the same diet as their mothers or placed on the alternative diet to give 4 dietary groups (C/C, HF/C, C/HF and HF/HF) which were studied at 15 or 30 weeks of age.Results: there were significant effects of maternal diet on offspring body weight (p<0.004), systolic blood pressure (p = 0.026) and endothelium-dependent relaxation to ACh (p = 0.004) and NO production (p = 0.005) measured in the femoral artery. With control for maternal diet there was also an effect of offspring post-weaning dietary fat to increase systolic blood pressure (p<0.0001) and reduce endothelium-dependent relaxation (p = 0.022) and ACh-mediated NO production (p = 0.007). There was also a significant impact of age (p<0.005). Redox balance was perturbed, with altered regulation of vascular enzymes involved in ROS/NO signalling.Conclusions: maternal consumption of a HF diet is associated with changes in vascular function and oxidative balance in the offspring of similar magnitude to those seen with consumption of a high fat diet post-weaning. Further, this disadvantageous vascular phenotype is exacerbated by age to influence the risk of developing obesity, raised blood pressure and endothelial dysfunction in adult lif

Evaluation of an a-Si EPID in direct detection configuration as a water-equivalent dosimeter for transit dosimetry

Purpose: A major problem associated with amorphous silicon (a-Si) electronic portal imaging devices (EPIDs) for transit dosimetry is the presence of a phosphor layer, which can introduce large deviations from water-equivalent behavior due to energy-dependent response and visible light scattering. In this study, an amorphous silicon EPID was modified to a direct detection configuration by removing the phosphor layer, and the accuracy of using it for transit dosimetry measurements was investigated for 6 and 18 MV treatment beams by comparison to ion-chamber in water measurements. Methods: Solid water and copper were both evaluated as buildup materials. Using the optimum buildup thickness in each case, effects of changes in radiation field size, source to detector distance, and patient/phantom thickness were investigated by comparison to reference measurements made by an ionization chamber on the central axis. The off-axis response of the imager was also investigated by comparison of EPID image profiles to dose profiles obtained by a scanning ionization chamber in a water tank with various thicknesses of slab phantoms, and an anthropomorphic phantom in the beam using Gamma evaluation (3%, 3 mm criteria). The imaging characteristics of the direct EPID were investigated by comparison to a commercial EPID using QC3V phantom, and by taking images of an anthropomorphic pelvic phantom containing fiducial gold markers. Results: Either 30 mm of solid water or 3.3 mm of copper were found to be the most suitable buildup thicknesses with solid water providing more accurate results. Using solid water buildup, the EPID response compared to the reference dosimeter within 2% for all conditions except phantom thicknesses larger than 25 cm in 6 MV beams, which was up to 6.5%. Gamma evaluation results comparing EPID profiles and reference ionization chamber profiles showed that for 6 and 18 MV beams, at least 91.8% and 90.9% of points had a Gamma<1 for all phantoms, respectively. But using copper buildup, the EPID response had more discrepancies from the ionization chamber reference measurements, including: More than 2% difference for small air gaps using 6 MV beams, up to 8% difference for phantom thicknesses larger than 25 cm in 6 MV beams, and large differences (up to 9.3%) for increasing phantom thicknesses in 18 MV beams. The percentage of points with Gamma<1 with copper buildup were at least 96.6% and 99.8% in 6 and 18 MV beams, respectively. Conclusions: The direct EPID performs as an ion-chamber detector for transit dosimetry applications in all geometries studied except for small discrepancies at 6 MV for thick phantoms. This can be ameliorated by the calibration of the EPID to dose at an intermediate phantom thickness. The major current limitation of the direct EPID is poor quality of images compared with the clinical configuration, which could be overcome by a method to interchange between imaging and dosimetry setups