There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.
Acute Radiation Syndrome ; blood ; immunology ; prevention & control ; Animals ; Blood Cells ; drug effects ; radiation effects ; Dose-Response Relationship, Drug ; Gamma Rays ; adverse effects ; Hydroxamic Acids ; therapeutic use ; Indoles ; therapeutic use ; Matrix Metalloproteinase Inhibitors ; therapeutic use ; Mice ; Radiation Injuries, Experimental ; blood ; immunology ; prevention & control ; Radiation-Protective Agents ; therapeutic use ; Spleen ; drug effects ; immunology ; radiation effects ; Survival Analysis ; Whole-Body Irradiation

Many Koreans, in addition to Japanese, were killed or injured by the atomic bombs detonated over Hiroshima and Nagasaki, Japan, in 1945. Our study examined noncancer diseases of Korean A-bomb survivors in residence at Hapcheon, Republic of Korea and evaluated whether they had significantly higher prevalence of noncancer diseases than non-exposed people. We evaluated a number of tests, including anthropometric measurements, blood pressure, blood chemistry, hepatitis B surface antigen, and urinalysis, of survivors (n=223) and controls (n=372). Univariate analysis revealed significantly lower fasting glucose and creatinine, and higher diastolic blood pressure, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen levels in the survivors than in the controls. The calculation of crude prevalence ratios (PRs) revealed that A-bomb survivors had a significantly higher prevalence of hypertension (PR, 1.16; 95% CI, 1.00-1.35) and chronic liver disease (2.20; 1.59-3.06) than controls. After adjusting for covariates (age, sex, body mass index, marital status, education, alcohol consumption, and smoking), A-bomb survivors had a significantly higher prevalence of hypertension (1.24; 1.06-1.44), chronic liver disease (2.07; 1.51-2.84), and hypercholesterolemia (1.79; 1.11-2.90) than controls. This study suggests that A-bomb exposure is associated with a higher prevalence of non-cancer diseases in Korean survivors.
Survivors ; Radioactive Fallout ; Radiation Injuries/diagnosis/*epidemiology ; Nuclear Warfare ; Neoplasms ; Middle Aged ; Male ; Korea ; Japan ; Humans ; Female ; Aged, 80 and over ; Aged ; Abnormalities, Radiation-Induced

OBJECTIVETo investigate the preventive effect of low-intensity ultrasound on osteoradionecrosis of jaws (ORNJ).

METHODSTwenty-five canines were randomly divided into experimental group (n=20) and control group (n=5). The canines in experimental group received radiation exposure, and then were randomly subdivided into group A (n=10) and group B (n=10). Control group did not undergo radiotherapy. One month after radiotherapy, the fourth mandibular premolars of all animals were extracted. Group B was immediately treated by low-intensity ultrasound for twenty days, group A and control group did not receive any treatment. Two months after tooth extraction, the formation of ORNJ was determined and the occurrence rate of ORNJ was compared between group A and B. The microstructure of the mandible and changes in microvascular density in group A and B were evaluated and compared with those of control group.

RESULTSAll animals in group B and group A developed ORNJ after prophylactic ultrasound was applied for twenty days. Although the imaging examination of bony density of group A and B were lower than normal animals in control group, bone density in group B was significantly better than group A. Micro-CT showed that the trabecular bone volume fraction, trabecular thickness, bone surface/bone volume and trabecular number in group B were respectively (0.187±0.029)%, (0.160±0.039) µm, (12.536±2.558)/mm, (1.227±0.192)/mm, which were all greater than group A [(0.103±0.014)%, (0.069±0.013) µm, (5.598±0.731)/mm, (0.522±0.064)/mm)] (P<0.05).

CONCLUSIONSAlthough the preventive application of low intensity ultrasound can not prevent the formation of ORNJ, but can significantly improve the symptoms of ORNJ.

Animals ; Bone Density ; radiation effects ; Dogs ; Jaw Diseases ; etiology ; prevention & control ; Mandible ; Osteoradionecrosis ; prevention & control ; Radiation Injuries, Experimental ; Random Allocation ; Tooth Extraction ; Ultrasonic Therapy ; methods ; X-Ray Microtomography

OBJECTIVETo establish a miniature pig model of mandibular osteoradionecrosis (ORN).

METHODSA single dose of irradiation (IR25 Gy, 28 Gy) was delivered via an electronic linear accelerator to the right mandible of 24 miniature pigs by utilizing three dimensional conformal radiotherapy (3D-CRT). The first molar of the mandible was extracted 2 months after radiation. Mandibular ORN was diagnosed through gross observation, X-ray film, CT, and histopathologic examination.

RESULTSAt 3-4 months after radiation, all animals suffered from mandibular ORN after dental extraction. The symptoms of ORN were more severe in the 28 Gy group than in the 25 Gy group.

CONCLUSIONA miniature pig model of mandibular ORN can be established through 25 Gy irradiation + dental extraction.

Animals ; Mandible ; Mandibular Diseases ; pathology ; Molar ; Osteoradionecrosis ; pathology ; Particle Accelerators ; Radiation Injuries, Experimental ; pathology ; Radiotherapy, Conformal ; adverse effects ; Swine ; Swine, Miniature ; Tooth Extraction

BACKGROUNDIrradiation dose and volume are the major physical factors of radiation-induced lung injury. The study investigated the relationships between the irradiation dose and volume in radiation-induced lung injury by setting up a model of graded volume irradiation of the rat lung.

METHODSAnimals were randomly assigned to three groups. The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume. The treatment plan for the three groups was: group 1 received a "high dose to a small volume" (25% volume group) with the mean irradiation volume being 1.748 cm(3) (25% lung volume); the total dose and mean lung dose (MLD) were 4610 cGy and 2006 cGy, respectively (bilateral AP-PA fields, source to axis distance (SAD) = 100 cm, 6MVX, single irradiation); Group 2 received a "low dose to a large volume" (100% volume group) with the mean irradiation volume being 6.99 cm(3) (100% lung volume); the total dose was 1153 cGy. MLD was 2006 cGy, which was the same as that of group 1 (bilateral AP-PA fields, SAD = 100 cm, 6MVX, single irradiation); Group 3 was a control group. With the exception of receiving no irradiation, group 3 had rest steps that were the same as those of the experimental groups. After irradiation, functional, histopathological, and CT changes were compared every two weeks till the 16th week.

RESULTSFunctionally, after irradiation breath rate (BR) increases were observed in both group 1 and group 2, especially during the period of 6th - 8th weeks. The changes of BR in the 100% volume group were earlier and faster. For the 25% volume group, although pathology was more severe, hardly any obvious increase in BR was observed. Radiographic changes were observed during the early period (the 4th week) and the most obvious changes manifested during the mediated period (the 8th week). The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group, and ground glass opacity and patchy consolidation were presented in the 25% volume group without pleural effusion, pleural thickening, and lung shrinking. Morphologically, the 100% volume group mainly presented signs of vascular damage, including signs of vascular wall edemas, hypertrophy, and sclerosis. The 25% volume group mainly presented with erythrocyte cell exudation, inflammation, and parenchymal damage.

CONCLUSIONSThe delivery of a small dose of radiation to a large volume is not safe. A low dose smeared out over large volumes, albeit reversible, may lead to fatal respiratory dysfunction. Damage to the lung may be more dependent on the volume of irradiation than on the radiation dose. Clinically, the safest approach is to limit both the volume of the irradiated normal lung and the amount of received radiation.

Animals ; Dose-Response Relationship, Radiation ; Lung ; radiation effects ; Lung Injury ; etiology ; Radiation Injuries, Experimental ; Rats ; Rats, Wistar

OBJECTIVETo observe the morphological changes and the regenerating ability of the fungiform papillae and taste buds after 60Co radiation with clinical doses in rats.

METHODSThe heads, faces and necks of 30 SD rats were radiated with a large dose and one time of 60Co in the clinical radiation. The general living condition and the number and shape of the fungiform papillae and taste buds of the tongues were observed after the radiation in rats.

RESULTSIn the group of 60Co radiation, the animals had wilting, decreasing appetite, losing weight. The heads, faces and necks of animals appeared redness, peeling of hair, increasing of secretions in 5 days after the 60Co radiation. The changes reached the summit in 10 days and the general living condition of the animals recovered in 60 days. The fungiform papillae and taste buds of the animals appeared degeneration, atrophy and collapsing in 5 days after the 60Co radiation. The injuries reached the summit in 10-20 days and the fungiform papillae and taste buds regenerated partially, and the some atrophied fungiform papillae and taste buds were not regenerated in 60 days.

CONCLUSIONThe damage to fungiform papillae and taste buds of tongue following the 60Co radiation with the clinical doses was very serious. The damaged fungiform papillae and taste buds can regenerate partially, but not completely.

Animals ; Radiation Injuries, Experimental ; pathology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Taste Buds ; pathology ; radiation effects ; Tongue ; pathology ; radiation effects

OBJECTIVETo investigate the ultrastructural variation of the facial nerve of rabbit with different dosage of (125)I seed brachytherapy.

METHODSFifty-four big ear rabbits were divided into 3 groups randomly and given 40 Gy, 80 Gy, 120 Gy respectively. Radioactive seeds were implanted in one side of parotid gland, the other side was implanted with vacant shell as a control group. The facial nerves were obtained 2, 4, 6 months respectively after operation and the histological ultrastructural changes observed by electromicroscope.

RESULTSIn the control group, epineurium was continuous, there was slight pitting edema under the epineurium, and axonal myelin was loose. In the test groups, there was slight pitting edema under the epineurium, and axonal myelin sheath was loose at 4th month. Macrophage and regenerated fibers were found in the 80 Gy group and myelin sheath lamellar separation, regeneration of nerve in the 120 Gy dosage. The myelin sheath lamellar was separated and axonal myelin loose in the test group at 6th month. Myelin sheath amellar separation and edema under the epineurium were found in the group of 80 Gy and 120 Gy.

CONCLUSIONSThe ultrastructure of the facial nerve is damaged by the dosage of 40 Gy, 80 Gy brachytherapy with (125)I seeds. The higher dosage the nerve receives, the more serious the damage will be. Both of the epineurium and axonal myelin sheath are integral and continuous 6 months after operation with dosage of 120 Gy.

Animals ; Brachytherapy ; Dose-Response Relationship, Radiation ; Facial Nerve ; radiation effects ; ultrastructure ; Female ; Iodine Radioisotopes ; administration & dosage ; radiation effects ; Male ; Rabbits ; Radiation Injuries, Experimental ; pathology ; Random Allocation

OBJECTIVETo study the effect of radiation injury on nitric oxide (NO) concentration in mouse peripheral blood and liver.

METHODSNIH mice were subjected to gamma-ray exposure at 9.0 Gy and transferred immediately in room temperature condition. NO concentrations in the liver and peripheral blood were examined before and at different time points after the exposure.

RESULTSCompared to that before exposure, NO concentration in the peripheral blood and liver significantly increased after gamma-ray exposure. NO concentration in the peripheral blood began to increase 3 h after the exposure, but that in the liver increased till 6 h after the exposure.

CONCLUSIONRadiation can cause the increase of NO concentration in the peripheral blood and liver, but different tissues may exhibit different response intensities to radiation.

Animals ; Gamma Rays ; Liver ; metabolism ; radiation effects ; Male ; Mice ; Nitric Oxide ; blood ; metabolism ; Radiation Injuries, Experimental ; blood ; metabolism ; Time Factors

OBJECTIVE: To observe histopathologic changes of irradiated guinea pigs' nasal mucosa treated with intranasal corticosteroids and to study the radioprotective effect of intranasal corticosteroids. METHOD: Fifty health guinea pigs nasal parts were performed irradiation by the WDVE-6MeV linear accelerator. They had accepted 5 Gy one time per week for three weeks through X-ray irradiating to establish the animal irradiation injury model. After that, they were divided into 2 groups randomly: the control group and the administration group and each group had 25 guinea pigs. The administration group received intranasal corticosteroids on the second day after three weeks irradiation, 5 animals per one group were sacrificed randomly at 1 W, 1 M, 2 M, 3 M, 4 M after administration, the histopathologic changes were observed under optical, scanning electron and transmission electron microscope respectively. RESULT: Using intranasal corticosteroids after irradiation, the early inflammatory reaction of the administration group was milder than the control group. With the drug being given constantly, the recovery of epithelial cell with irradiated damage was accelerated and the coverage rate of cilia went up obviously; After four months, the coverage rate of cilia had risen to 72.9%; But, for the control group, the coverage rate of cilia is only 50.2%. The atrophy of submucosal glandular organ was lessened and they displayed some extent secretory function. The reparation was accelerated as time went by. CONCLUSION Irradiation brought about serious injury on guinea pigs' nasal mucosa. But, the injury was lessen after using intranasal corticosteroids. Intranasal corticosteroids play the role of radioprotection for the irradiated nasal mucosa.
Adrenal Cortex Hormones ; pharmacology ; Animals ; Guinea Pigs ; Nasal Mucosa ; drug effects ; pathology ; radiation effects ; Radiation Injuries, Experimental ; prevention & control

OBJECTIVETo assess the radioactive damage induced by interstitial 125I seed implantation to the rabbit urethra.

METHODSWe implanted 24 rabbits with 125I seeds 1.0 cm to the urethra at the radiation dose of 14.8 MBq (Group A), 29.6 MBq (Group B) and 44.4 MBq (Group C), while a non-radioactive seed was implanted near the urethra of the controls (Group D). Four weeks later, we detected the radiation-induced pathological and morphological changes in the urethra by H&E, light microscopy and electron microscopy.

RESULTSFour weeks after the implantation, no obvious histopathological and ultrastructural changes were observed in the urethral tissues of the experimental rabbits as compared with the control group. The scores on the radioactive damages to the urethra obtained by light microscopy were (2.20 +/- 0.18), (2.23 +/- 0.15), (2.27 +/- 0.10) and (2.10 +/- 0.17) respectively in Group A, B, C and D, with no significant differences between the first three groups and the control (P > 0.05). And the scores on the FlaMeng semi- quantitative analysis of mitochondria in the experimental groups were (1.23 +/- 0.13), (1.34 +/- 0.25) and (1.41 +/- 0.30) respectively, not significantly different from (1.12 +/- 0.13) the control (P > 0. 05).

CONCLUSIONThe radioactive damage induced by 125I seeds to the urethra increases with the enhanced radiation dose. Intraoperative implantation of 125I seeds at the prescription dose has no obvious adverse effect on the rabbit urethra.

Animals ; Dose-Response Relationship, Radiation ; Iodine Radioisotopes ; adverse effects ; Male ; Microscopy, Electron ; Rabbits ; Radiation Injuries, Experimental ; etiology ; pathology ; Urethra ; pathology ; radiation effects ; ultrastructure