[en] Purpose: Reducing intraluminal proteolytic activity attenuates intestinal radiation toxicity. This study assessed whether pharmacological inhibition of exocrine pancreatic secretion protects against early and delayed radiation enteropathy in a preclinical rat model. Methods and Materials: Rat ileum was sham-irradiated or exposed to 16 once-daily 4.2 Gy fractions of X-radiation. Vehicle or somatostatin analogue (octreotide, 2 μg/kg/hr) were administered from 2 days prior to 10 days after the end of irradiation. Mucosal injury was monitored noninvasively by assessment of granulocyte transmigration. Radiation injury was assessed at 2 weeks (early phase) and 26 weeks (chronic phase) using quantitative histopathology, immunohistochemistry, and morphometry. Results: Octreotide decreased granulocyte transmigration (p < 0.0006), reduced accumulation of myeloperoxidase-positive cells at 2 weeks (p = 0.0002), attenuated structural injury at 2 weeks (p = 0.04) and 26 weeks (p = 0.02), preserved mucosal surface area at 2 weeks (p = 0.0008) and 26 weeks (p = 0.0008), and reduced intestinal wall thickening at 26 weeks (p = 0.002). Octreotide did not affect granulocyte transmigration, histology, or mucosal surface area in sham-irradiated controls. Conclusion: These results demonstrate the importance of consequential mechanisms in the pathogenesis of chronic radiation enteropathy. Short-term octreotide administration ameliorates acute radiation-induced mucosal injury, as well as chronic structural changes, and should be subject to further preclinical and clinical testing

[en] Bone marrow and skin allografts from the same donor were transplanted to rats inflicted with 8 Gy γ-radiation combined with third degree burns of 15% body surface area within 6 hr post injury. Pathological changes of hematopoietic tissues and skin allografts were studied. All injured controls died within 7 days post injury without bone marrow regeneration; 50% of treated rats survived with living skin allografts on 50th day post injury. On days 100 and 480 post operation, grafted skin still survived well on recipients with normal ultrastructure. Epidermic cells of skin allografts proliferated on day 5, developed and repaired on day 10. Histological structure of the skin returned to normal on day 30 post operation. The regeneration of bone marrow appeared on 5th day, increased markedly on day 10, and almost completed on day 15 after bone marrow transplantation. However, the regeneration of lymphocytes in cortex of spleen and lymph nodes did not appear until day 15 of BMT. The results show that bone marrow and skin allograft transplantation at early time post injury in most severe combined radiation-burn injury have tremendous beneficial effects, and the skin allograft can survive for a long time

[en] Vascular endothelial cells are very sensitive to ionizing radiation, and it is important to develop effective prevent agents and measures in radiation exposure protection. In the present study, the protective effects of atorvastatin on irradiated human umbilical vein endothelial cells (HUVEC) and the possible mechanisms were explored. Cultured HUVEC were treated by atorvastatin at a final concentration of 10 μmol/ml for 10 minutes, and then irradiated at a dose of 2 Gy or 25 Gy. Twenty-four hours after irradiation, apoptosis of HUVEC was monitored by flow cytometry, and the expression of thrombomodulin (TM) and protein C activation in HUVEC was respectively assessed by flow cytometry and spectrophotometry. After treatment with atorvastatin for 24 h, the rate of cell apoptosis decreased by 6% and 16% in cells irradiated with 2 Gy and 25 Gy, respectively. TM expression increased by 77%, 59%, and 61% in untreated cells, 2 Gy irradiation-treated cells, and 25 Gy irradiation-treated cells, respectively. The protein C levels in 2 Gy and 25 Gy irradiation-treated cells were reduced by 23% and 34% when compared with untreated cells, but up-regulated by 79% and 76% when compared with cells which were irradiated and treated with atorvastatin. In conclusion, these data indicate that atorvastatin exerts protective effects on irradiated HUVEC by reducing apoptosis by up-regulating TM expression and enhancing protein C activation in irradiated HUVEC. (author)

[en] Objective: To analyse the cell proliferation, cell cycle and the expression of IL-3, IL-3Rα in Dami cells after exposure to ⁶⁰Co γ rays. Methods: After Dami cells were exposed to ⁶⁰Co γ rays, the cell cycle and proliferation of Dami cells were analyzed by means of MTT and flow cytometry. The IL-3 and the IL- 3Rα expressions were detected by RT-PCR at 24 h after irradiation. Results: The irradiated Dami cells showed dose-dependent proliferative inhibition and G₀/G₁ block. Expressions of IL-3 and IL-3Rα mRNA in Dami after irradiation at doses of 5, 10, and 15 Gy were significantly lower than those in normal Dami cells (P<0.05). Their expressions showed reverse correlation with the dose. Conclusions: γ rays irradiation change the cell cycle, inhibits cell proliferation, IL-3 and IL-3Rα mRNA expression, suggesting that the abnormal expressions of IL-3 and IL-3Rα in Dami cells are involved in the injury of hemopoiesis by different doses of ⁶⁰Co γ ray irradiation. (authors)

No abstract available

[en] Objective: To determine the distribution of uranium in rats with fragments of depleted uranium (DU) implanted in muscle and the residual influence of removed uranium fragments. Methods: Rats were surgically implanted with sterilized DU within muscle under anesthesia. At 5 days after implantation, the fragments were removed from rats in several groups while they were not removed in the other groups. At 1, 3, 7, 15, 20, and 26 days after implantation, tissue samples were collected from all animals. Using a laser phosphorescence analyzer, uranium levels were measured. Results: At all time points, uranium concentrations in all samples in the implanted rats were significantly greater than those in the control group, especially in kidney, ovary and sternum. Uranium concentrations in most samples in the implanted rats were greater than in the rats with removed fragments. Conclusion: Kidney, ovary and sternum are the primary organs for uranium redistributed from intramuscularly embedded DU fragments. Removing DU fragments and excising the surrounding muscles would reduce the uranium concentrations in tissues in the implanted rats

[en] Objective: To explore the protective effect of atorvastatin on irradiated endothelium and the thrombomodulin (TM) expression. Methods: Cultured human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were treated by atorvastatin at the final concentration of 10 μmol/ml for 10 min, and then irradiated with 2 and 25 Gy. Cell cycles status and TM expression were quantitatively measured by flow cytometry 24 hours after irradiation. Protein C activation in endothelial cells was also assessod. Results: After administration with atorvastatin for 24 h, the TM expression increased by 77%, 59% and 61% in normal control group, 2 Gy group and 25 Gy group, respectively (t=27.395, 26.420, 58.065; P=0.000). The protein C levels decreased by 23% and 34% compared with the normal group post-irradiation to 2 and 25 Gy, but increased by 79% and 76% compared with the irradiated control group after administration with atorvastatin. The rates of cell apoptosis decreased by 6% and 16% in 2 Gy and 25 Gy groups, respectively after administration with atorvastatin for 24 h (t=4.178, 17.863; P=0.000). Conclusions: Atorva statin can protect endothelia cell from irradiation-induced apeptosis by increasing TM expression and protein C activation. (authors)

[en] Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor β immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent