Optimal LDR to Protect the Kidney From Diabetes: Whole-Body Exposure to 25 mGy X-rays Weekly for 8 Weeks Efficiently Attenuates Renal Damage in Diabetic Mice.

To explore an optimal frequency of whole-body low-dose radiation (LDR) to protect the kidney from diabetes, type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic or age-matched normal mice received whole-body exposure to 12.5 or 25 mGy either every other day or weekly for 4 or 8 weeks. Diabetes decreased the urinary creatinine and increased the microalbumin in urine, renal accumulation of 3-nitrotyrosine and 4-hydroxynonenal, and renal expression of collagen IV and fibronectin. All these renal pathological and functional changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens. However, whole-body exposure of diabetic mice to 25 mGy weekly and to 12.5 mGy every other day for 8 weeks provided a better prevention of diabetic nephropathy than other LDR regimens. Furthermore, whole-body exposure to 25 mGy weekly for 8 weeks showed no detectable effect on the kidney of normal mice, but whole-body exposure to normal mice at 12.5 mGy every other day for 8 weeks increased urinary microalbumin and renal expression of collagen IV and fibronectin. These results suggest that whole-body exposure to LDR at 25 mGy weekly is the optimal condition of LDR to protect the kidney from diabetes.

Alterations of MicroRNA Expression in the Liver, Heart, and Testis of Mice Upon Exposure to Repeated Low-Dose Radiation.

MicroRNAs (miRs), which regulate target gene expression at the post-transcriptional level, play a crucial role in inducing biological effects upon high-dose ionizing radiation. Yet, the miR expression profiles in response to repeated low-dose radiation (LDR) in vivo have not been elucidated. This study investigated the response profiles of 11 miRs with functions involved in metabolism, DNA damage and repair, inflammation, and fibrosis in mouse liver, heart, and testis upon repeated LDR exposure for 4 months. The expression profiles were evaluated using stem-loop quantitative reverse transcription polymerase chain reaction immediately and at 2 months after LDR exposure. The expression profiles varied significantly at both time points. At the organ level, the heart was the most affected, followed by the liver and testis, in which significant miR upregulation related to DNA damage response was found. Metabolism-related miRs decreased in the liver and increased in the testis. The current results showed immediate and long-lasting alterations in the miR expression profiles in response to repeated LDR in different organs.

Repeated Whole-Body Exposure to Low-Dose Radiation Combined With Topical Application of Basic Fibroblast Growth Factor and Zinc Accelerates Wound Healing in Diabetic Rats.

We reported the acceleration of skin wound healing in diabetic rats by repeated exposure to low-dose radiation (LDR). Here, we explored whether the wound healing could be further improved when LDR was combined with a topical application of basic fibroblast growth factor (bFGF) or zinc. Wounds were established on the backs of type 1 diabetic rats induced by a single injection of streptozotocin. Rats were treated daily with normal saline (Diabetes), LDR, bFGF, zinc, or combined 3 treatments for 5 consecutive days with a 2-day break between each consecutive 5-day treatment. Changes in wound size, histopathology, and microvessel density were assessed on days 5, 10, and 15, respectively, once treatment is started. All treatment regimens significantly accelerated skin wound healing, tissue remodeling, and new vessel formation compared to diabetes group. However, the combined LDR plus bFGF and zinc provided a better beneficial effect on wound healing than either one of these treatments alone. Further, we found that the effects of LDR and bFGF were similar, whereas zinc alone induced a weaker response. Our results suggest that whole-body LDR plus the topical application of bFGF and zinc can further accelerate wound healing in diabetic rats.

Commissioning of a motion system to investigate dosimetric consequences due to variability of respiratory waveforms.

A commercially available six-dimensional (6D) motion system was assessed for accuracy and clinical use in our department. Positional accuracy and respiratory waveform reproducibility were evaluated for the motion system. The system was then used to investigate the dosimetric consequences of respiratory waveform variation when an internal target volume (ITV) approach is used for motion management. The maximum deviations are 0.3 mm and 0.22° for translation and rotation accuracy, respectively, for the tested clinical ranges. The origin reproducibility is less than±0.1 mm. The average differences are less than 0.1 mm with a maximum standard deviation of 0.8 mm between waveforms of actual patients and replication of those waveforms by HexaMotion for three breath-hold and one free-breathing waveform. A modified gamma analysis shows greater than 98% agreement with a 0.5 mm and 100 ms threshold. The motion system was used to investigate respiratory waveform variation and showed that, as the amplitude of the treatment waveform increases above that of the simulation waveform, the periphery of the target volume receives less dose than expected. However, by using gating limits to terminate the beam outside of the simulation amplitude, the results are as expected dosimetrically. Specifically, the average dose difference in the periphery between treating with the simulation waveform and the larger amplitude waveform could be up to 12% less without gating limits, but only differed 2% or less with the gating limits in place. The general functionality of the system performs within the manufacturer's specifications and can accurately replicate patient specific waveforms. When an ITV approach is used for motion management, we found the use of gating limits that coincide with the amplitude of the patient waveform at simulation helpful to prevent the potential underdosing of the target due to changes in patient respiration.