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Sample records for delayed radiation injury

  1. Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

    SciTech Connect

    Haydont, Valerie; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine |. E-mail: vozenin@igr.fr

    2007-08-01

    Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.

  2. A histological and flow cytometric study of dog brain endothelial cell injuries in delayed radiation necrosis

    SciTech Connect

    Yamaguchi, N.; Yamashima, T.; Yamashita, J. )

    1991-04-01

    The pathogenesis of delayed cerebral radiation necrosis was studied histologically and biochemically in 25 dogs with special attention to vascular endothelial cell injuries. The dogs were sacrificed 3 to 30 months after irradiation with a single dose of 15 Gy to the head. Brain specimens were appropriately fixed for light and electron microscopic studies, and capillary endothelial cells were isolated for flow cytometric study. The endothelial cells were stained with acridine orange, then the cell ratios in the reproductive phase (S + G2 + M) were investigated with flow cytometry. Thereafter, Feulgen hydrolysis and computer analysis of the hydrolysis curves were performed to examine the qualitative changes in deoxyribonucleic acid (DNA) of endothelial cells after irradiation. Under light microscopy, spongy degeneration with small cell infiltration was observed, especially in the frontal white matter, at 6 months after irradiation. At 9 months, necrotic foci appeared and developed until 15 months after irradiation. Blood vessels around the necrotic area showed luminal narrowing with endothelial hyperplasia and proliferation. At 30 months, no fresh necrotic lesions were observed. Under electron microscopy, endothelial cells of capillaries and small vessels around the necrotic area showed an increase of pinocytosis, and in the nuclei there was an increase of infoldings and euchromatin. The cell ratios in the reproductive phase were 14.5% to 23.3% (maximum at 9 months) in the irradiated group compared to 6.4% in the control group. The rate constant of apurinic acid production, a parameter correlating with DNA transcriptional activity, was minimum at 3 months and maximum at 9 months after irradiation. The data suggest that impairment of the microcirculation plays an important role in the pathogenesis of delayed radiation necrosis.

  3. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    PubMed

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated. PMID:27682899

  4. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    PubMed

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

  5. Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids

    SciTech Connect

    Roden, D.; Bosley, T.M.; Fowble, B.; Clark, J.; Savino, P.J.; Sergott, R.C.; Schatz, N.J. )

    1990-03-01

    Thirteen patients with delayed radiation injury to the optic nerves and chiasm were treated with hyperbaric oxygen (HBO) and corticosteroids. These patients experienced painless, abrupt loss of vision in one (6 patients) or both (7 patients) eyes between 4 and 35 months after receiving radiation doses of at least 4500 cGy to the region of the chiasm. Diagnostic evaluation including neuro-imaging and lumbar puncture showed no recurrent tumor and no other cause for visual loss. No patient's vision improved during treatment or follow-up lasting between 1 and 4 years. There were no serious complications of treatment.

  6. Repeated delayed onset cerebellar radiation injuries after linear accelerator-based stereotactic radiosurgery for vestibular schwannoma: case report.

    PubMed

    Ujifuku, Kenta; Matsuo, Takayuki; Toyoda, Keisuke; Baba, Shiro; Okunaga, Tomohiro; Hayashi, Yukishige; Kamada, Kensaku; Morikawa, Minoru; Suyama, Kazuhiko; Nagata, Izumi; Hayashi, Nobuyuki

    2012-01-01

    A 63-year-old woman presented with right hearing disturbance and vertigo. Magnetic resonance (MR) imaging revealed the presence of right vestibular schwannoma (VS). Stereotactic radiosurgery (SRS) was performed with a tumor marginal dose of 14 Gy using two isocenters. She was followed up clinically and neuroradiologically using three-dimensional spoiled gradient-echo MR imaging. She experienced temporal neurological deterioration due to peritumoral edema in her right cerebellar peduncle and pons for a few months beginning 1.5 years after SRS, when she experienced transient right facial dysesthesia and hearing deterioration. Ten years after SRS, the patient presented with sudden onset of vertigo, gait disturbance, diplopia, dysarthria, and nausea. MR imaging demonstrated a new lesion in the right cerebellar peduncle, which was diagnosed as radiation-induced stroke. The patient was followed up conservatively and her symptoms disappeared within a few months. Multiple delayed onset radiation injuries are possible sequelae of SRS for VS. PMID:23269054

  7. Treatment of Radiation Injury

    PubMed Central

    Akita, Sadanori

    2014-01-01

    Significance: Radiation exposure as a result of radiation treatment, accident, or terrorism may cause serious problems such as deficiency due to necrosis or loss of function, fibrosis, or intractable ulcers in the tissues and organs. When the skin, bone, oral mucous membrane, guts, or salivary glands are damaged by ionizing radiation, the management and treatment are very lengthy and difficult. Critical Issues: In severe and irreversible injuries, surgery remains the mainstay of treatment. Several surgical procedures, such as debridement, skin grafting, and local and free-vascularized flaps, are widely used. Recent Advances: In specific cases of major morbidity or in high-risk patients, a newly developed therapy using a patient's own stem cells is safe and effective. Adipose tissue, normally a rich source of mesenchymal stem cells, which are similar to those from the bone marrow, can be harvested, since the procedure is easy, and abundant tissue can be obtained with minimal invasiveness. Future Directions: Based on the molecular basis of radiation injuries, several prospective treatments are under development. Single-nucleotide polymorphisms focus on an individual's sensitivity to radiation in radiogenomics, and the pathology of radiation fibrosis or the effect of radiation on wound healing is being studied and will lead to new insight into the treatment of radiation injuries. Protectors and mitigators are being actively investigated in terms of the timing of administration or dose. PMID:24761339

  8. Radiation Injury to the Brain

    MedlinePlus

    ... Hits since January 2003 RADIATION INJURY TO THE BRAIN Radiation treatments affect all cells that are targeted. ... fractions, duration of therapy, and volume of [healthy brain] nervous tissue irradiated influence the likelihood of injury. ...

  9. Radiation injury of bone

    SciTech Connect

    Shimanovskaya, K.; Shiman, A.D.

    1983-01-01

    This monograph is devoted to the characteristics of radiation injuries arising in hitherto unaffected parts of the skeleton during the treatment of neoplasms by radiotherapy. These changes frequently accompany the beneficial effects of radiotherapy, and can easily be misunderstood in the absence of any clear idea of their character. An understanding of the mechanism and conditions of appearance of radiation injuries of the skeleton and a knowledge of their clinical and radiological features are essential for physicians and surgeons caring for patients who have been treated by using radiotherapy and for experimental scientists whose work involves such methods. The effect of irradiation is determined by the topographical relations within the irradiated object, the character of distribution of the dose, and the size of the dose. The radiation injuries of the skeleton described in the book were observed during the treatment of carcinoma of the breast, lung, esophagus, and uterus, of malignant tumors in the mouth, certain pituitary tumors, and hemangiomas of the skin in children, by means of ionizing radiation obtained from various sources. A few observations relate to patients treated for certain other diseases. The text is illustrated by roentgenograms on the basis of which the diagnoses were made and the course of the lesion was subsequently confirmed, and also by operative and histological specimens. The book also contains many schemes drawn from roentgenograms.

  10. Diagnosis of delayed cerebral radiation necrosis following proton beam therapy

    SciTech Connect

    Kaufman, M.; Swartz, B.E.; Mandelkern, M.; Ropchan, J.; Gee, M.; Blahd, W.H. )

    1990-04-01

    A 27-year-old man developed delayed cerebral radiation necrosis following proton beam therapy to an arteriovenous malformation. Neuroimaging with technetium 99m diethylenetriamine penta-acetic acid and positron emission tomographic scanning with fludeoxyglucose F 18 aided in his evaluation. Significant improvement of his neurologic deficits resulted from corticosteroid therapy. Clinical resolution was corroborated by serial computed tomographic scans demonstrating regression of the abnormality (a mass lesion). Various facets of radiation injury are discussed, including pathogenesis, risk factors, diagnosis, and therapy.

  11. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

    PubMed

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  12. Delayed kidney injury following coronary angiography

    PubMed Central

    WANG, FENG; PENG, CHENG; ZHANG, GUANGYUAN; ZHAO, QING; XUAN, CHANGYOU; WEI, MENG; WANG, NIANSONG

    2016-01-01

    It is occasionally observed that patients without contrast-induced nephropathy (CIN) develop kidney injury within 1–6 months after coronary angiography (CAG), termed delayed CIN or delayed kidney injury (DKI) following CAG. The present study aimed to investigate the associated risk factors of delayed CIN and its possible pathogenesis. Subjects with CAG or coronary stenting from January 2008 to December 2009 were studied. A retrospective survey on DKI after CAG was conducted and the risk factors were analyzed. There were 436 cases receiving CAG with complete medical records enrolled in the present cohort, in which the DKI incidence was 7.1% (31/436). Patients with DKI after CAG exhibited lower hemoglobin (121.2±17.3 vs. 133.8±18.6 g/l), estimated glomerular filtration rate (eGFR; 66.4±30.2 vs. 71.9±28.6 ml/min), higher serum creatinine (110.9±43.2 vs. 91.7±37.6 µmol/l), higher rate of heart failure (22.6 vs. 5.4%) and 300 mg aspirin therapy (29 vs. 5.7%) compared with non-DKI patients (all P<0.05). However, no differences were observed in morbidities of diabetes, hypertension, hyperlipidemia and proteinuria, or in the treatments with angiotensin converting enzyme (ACE) inhibitors/angiotensin II receptor-1 blockers (ARBs), diuretics, statins and other anti-platelets between the two groups (P>0.05). Logistic regression revealed that anemia, heart failure and 300 mg aspirin intake were risk factors of DKI (P<0.05), while the contrast level, isotonic contrast, diabetes, ACE inhibitors/ARBs, eGFR and other factors were not associated with DKI (P>0.05). Heart dysfunction and 300 mg aspirin therapy may contribute to DKI after CAG, and iodinated contrast media administration is not a risk factor. PMID:27347090

  13. Delayed facial palsy after head injury.

    PubMed Central

    Puvanendran, K; Vitharana, M; Wong, P K

    1977-01-01

    Where facial palsy follows head injury after many days, the mechanism is not clear, and there has been no detailed study on this condition. In this prospective study, an attempt is made to estimate this complication of head injury, and to study its pathogenesis, natural history, prognosis, and sequelae which differ markedly from Bell's palsy. It has a much worse prognosis and so surgical decompression should be considered early in this condition. Images PMID:301556

  14. Delayed torrential haemorrhage after firearm injury

    PubMed Central

    Kumar, Pankaj; Singhal, Maneesh; Sagar, Sushma; Gupta, Amit

    2014-01-01

    A 30-year-old man was referred to us after 48 days of gunshot injury to left groin, with torrential bleeding from a pseudoaneurysm of the left external iliac artery. He was successfully managed with a team of specialists involving trauma surgeon, vascular and plastic surgeon, general surgeons and intervention radiologist with the help of critical care specialists. He required judicious debridement, a transverse rectus abdominis musculocutaneous flap, stenting of the external iliac artery, repair of the external iliac vein and ligation of the bilateral internal iliac artery. He had prolonged intensive care unit stay with open abdomen requiring specialised care. Errors in regular assessment of patient by clinical and radiological examination along with failure in early adequate debridement were responsible for trauma suffered by him. Though it is a rare injury, these devastating complications can occur after any gunshot injury and proper management guidelines must be established. PMID:24810442

  15. Delayed Radiation-Induced Vasculitic Leukoencephalopathy

    SciTech Connect

    Rauch, Philipp J.; Park, Henry S.; Knisely, Jonathan P.S.; Chiang, Veronica L.; Vortmeyer, Alexander O.

    2012-05-01

    Purpose: Recently, single-fraction, high-dosed focused radiation therapy such as that administered by Gamma Knife radiosurgery has been used increasingly for the treatment of metastatic brain cancer. Radiation therapy to the brain can cause delayed leukoencephalopathy, which carries its own significant morbidity and mortality. While radiosurgery-induced leukoencephalopathy is known to be clinically different from that following fractionated radiation, pathological differences are not well characterized. In this study, we aimed to integrate novel radiographic and histopathologic observations to gain a conceptual understanding of radiosurgery-induced leukoencephalopathy. Methods and Materials: We examined resected tissues of 10 patients treated at Yale New Haven Hospital between January 1, 2009, and June 30, 2010, for brain metastases that had been previously treated with Gamma Knife radiosurgery, who subsequently required surgical management of a symptomatic regrowing lesion. None of the patients showed pathological evidence of tumor recurrence. Clinical and magnetic resonance imaging data for each of the 10 patients were then studied retrospectively. Results: We provide evidence to show that radiosurgery-induced leukoencephalopathy may present as an advancing process that extends beyond the original high-dose radiation field. Neuropathologic examination of the resected tissue revealed traditionally known leukoencephalopathic changes including demyelination, coagulation necrosis, and vascular sclerosis. Unexpectedly, small and medium-sized vessels revealed transmural T-cell infiltration indicative of active vasculitis. Conclusions: We propose that the presence of a vasculitic component in association with radiation-induced leukoencephalopathy may facilitate the progressive nature of the condition. It may also explain the resemblance of delayed leukoencephalopathy with recurring tumor on virtually all imaging modalities used for posttreatment follow-up.

  16. Delay to orthopedic consultation for isolated limb injury

    PubMed Central

    Rouleau, Dominique M.; Feldman, Debbie Ehrmann; Parent, Stefan

    2009-01-01

    ABSTRACT OBJECTIVE To describe referral mechanisms for referral to orthopedic surgery for isolated limb injuries in a public health care system and to identify factors affecting access. DESIGN Cross-sectional survey. SETTING Orthopedic surgery service in a level 1 trauma centre in Montreal, Que. PARTICIPANTS We conducted a prospective study of 166 consecutive adults (mean age 48 years) referred to orthopedic surgery for isolated limb injuries during a 4-month period. MAIN OUTCOME MEASURES Self-reported data on the nature of the trauma, the elapsed time between injury and orthopedic consultation, the number and type of previous primary care consultations, sociodemographic characteristics, and the level of satisfaction with care. RESULTS Average time between the injury and orthopedic consultation was 89 hours (range 3 to 642), with an average of 68 hours (range 0 to 642) for delay between primary care consultation and orthopedic consultation. A total of 36% of patients with time-sensitive diagnoses had unacceptable delays to orthopedic consultation according to the Quebec Orthopaedic Association guidelines. Lower limb injury, consulting first at another hospital, living far from the trauma centre, patient perception of low severity, and having a soft tissue injury were associated with longer delays. CONCLUSION Identifying gaps and risk factors for slower access might help improve referral mechanisms for orthopedic consultation. PMID:19826162

  17. Protocol for the treatment of radiation injuries

    NASA Astrophysics Data System (ADS)

    Browne, D.; Weiss, J. F.; Macvittie, T. J.; Pillai, M. V.

    Despite adequate precautionary measures and high-quality safeguard devices, many accidental radiation exposures continue to occur and may pose greater risks in the future, including radiation exposure in the space environment. The medical management of radiation casualties is of major concern to health care providers. Such medical management was addressed at The First Consensus Development Conference on the Treatment of Radiation Injuries, Washington, DC, 1989. The conference addressed the most appropriate treatment for the hematopoietic and infectious complications that accompany radiation injuries and for combined radiation and traumatic/burn injuries. Based on the evidence presented at the conference, a consensus statement was formulated by expert physicians and scientists. The recommended therapies, including a suggested algorithm incorporating these recommendations for the treatment of radiation injuries, will be discussed.

  18. Combined injury syndrome in space-related radiation environments

    NASA Astrophysics Data System (ADS)

    Dons, R. F.; Fohlmeister, U.

    The risk of combined injury (CI) to space travelers is a function of exposure to anomalously large surges of a broad spectrum of particulate and photon radiations, conventional trauma (T), and effects of weightlessness including decreased intravascular fluid volume, and myocardial deconditioning. CI may occur even at relatively low doses of radiation which can synergistically enhance morbidity and mortality from T. Without effective countermeasures, prolonged residence in space is expected to predispose most individuals to bone fractures as a result of calcium loss in the microgravity environment. Immune dysfunction may occur from residence in space independent of radiation exposure. Thus, wound healing would be compromised if infection were to occur. Survival of the space traveler with CI would be significantly compromised if there were delays in wound closure or in the application of simple supportive medical or surgical therapies. Particulate radiation has the potential for causing greater gastrointestinal injury than photon radiation, but bone healing should not be compromised at the expected doses of either type of radiation in space.

  19. Surgical Reconstruction of Radiation Injuries

    PubMed Central

    Fujioka, Masaki

    2014-01-01

    Significance: Patients with cancer receive benefits from radiation therapy; however, it may have adverse effects on normal tissue such as causing radiation-induced ulcer and osteoradionecrosis. The most reliable method to treat a radiation ulcer is wide excision of the affected tissue, followed by coverage with well-vascularized tissue. As usual, radiation-induced skin ulcers are due to therapeutic irradiation for residual cancer or lymph nodes; the locations of radiation ulcers are relatively limited, including the head, neck, chest wall, lumbar, groin, and sacral areas. Thus, suitable reconstructive methods vary according to functional and aesthetic conditions. I reviewed the practices and surgical results for radiation ulcers over the past 30 years, and present the recommended surgical methods for these hard-to-heal ulcers. Recent Advances: At a minimum, flaps are required to treat radiation ulcers. Surgeons can recommend earlier debridement, followed by immediate coverage with axial-pattern musculocutaneous and fasciocutaneous flaps. Free flaps are also a useful soft tissue coverage option. The choice of flap varies with the location and size of the wounds. Critical Issues: The most crucial procedure is the complete resection of the radiation-affected area, followed by coverage with well-vascularized tissue. Future Directions: Recent developments in perforator flap techniques, which are defined as flaps with a blood supply from isolated perforating vessels of a stem artery, have allowed the surgeons to successfully resurface these difficult wounds with reduced morbidity. PMID:24761342

  20. Radiation-induced lung injury

    SciTech Connect

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  1. Radiation-Associated Liver Injury

    SciTech Connect

    Pan, Charlie C.; Kavanagh, Brian D.; Dawson, Laura A.; Li, X. Allen; Das, Shiva K.; Miften, Moyed; Ten Haken, Randall K.

    2010-03-01

    The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver.

  2. Radiation combined injury: overview of NIAID research.

    PubMed

    DiCarlo, Andrea L; Ramakrishnan, Narayani; Hatchett, Richard J

    2010-06-01

    The term "radiation combined injury" (RCI) is used to describe conditions where radiation injury is coupled with other insults such as burns, wounds, infection, or blunt trauma. A retrospective account of injuries sustained following the atomic bombing of Hiroshima estimates that RCI comprised approximately 65% of all injuries observed. Much of the research that has been performed on RCI was carried out during the Cold War and our understanding of the clinical problem RCI presents does not reflect the latest advances in medicine or science. Because concerns have increased that terrorists might employ radiological or nuclear weapons, and because of the likelihood that victims of such terrorism would experience RCI, the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health sponsored a meeting in 2007 to explore the state of the research in this area, identify programmatic gaps, and establish priorities for future research. As a follow-up to that meeting, in 2008 NIAID sponsored an initiative on RCI, leading to the award of several exploratory/developmental grants, the goals of which are to better understand biological synergy involved in RCI-induced damage, develop improved animal models for various type of RCI, and advance identification and testing of potential countermeasures to treat injuries that would be expected following a radiological or nuclear event. This program has already yielded new insight into the nature of combined injuries and has identified a number of novel and existing compounds that may be effective treatments for this condition.

  3. Radiation combined injury: overview of NIAID research.

    PubMed

    DiCarlo, Andrea L; Ramakrishnan, Narayani; Hatchett, Richard J

    2010-06-01

    The term "radiation combined injury" (RCI) is used to describe conditions where radiation injury is coupled with other insults such as burns, wounds, infection, or blunt trauma. A retrospective account of injuries sustained following the atomic bombing of Hiroshima estimates that RCI comprised approximately 65% of all injuries observed. Much of the research that has been performed on RCI was carried out during the Cold War and our understanding of the clinical problem RCI presents does not reflect the latest advances in medicine or science. Because concerns have increased that terrorists might employ radiological or nuclear weapons, and because of the likelihood that victims of such terrorism would experience RCI, the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health sponsored a meeting in 2007 to explore the state of the research in this area, identify programmatic gaps, and establish priorities for future research. As a follow-up to that meeting, in 2008 NIAID sponsored an initiative on RCI, leading to the award of several exploratory/developmental grants, the goals of which are to better understand biological synergy involved in RCI-induced damage, develop improved animal models for various type of RCI, and advance identification and testing of potential countermeasures to treat injuries that would be expected following a radiological or nuclear event. This program has already yielded new insight into the nature of combined injuries and has identified a number of novel and existing compounds that may be effective treatments for this condition. PMID:20445395

  4. Behavioral endpoints for radiation injury

    NASA Astrophysics Data System (ADS)

    Rabin, B. M.; Joseph, J. A.; Hunt, W. A.; Dalton, T. B.; Kandasamy, S. B.; Harris, A. H.; Ludewig, B.

    1994-10-01

    The relative behavioral effectiveness of heavy particles was evaluated. Using the taste aversion paradigm in rats, the behavioral toxicity of most types of radiation (including 20Ne and 40Ar) was similar to that of 60Co photons. Only 56Fe and 93Nb particles and fission neutrons were significantly more effective. Using emesis in ferrets as the behavioral endpoint, 56Fe particles and neutrons were again the most effective; however, 60Co photons were significantly more effective than 18 MeV electrons. These results suggest that LET does not completely predict behavioral effectiveness. Additionally, exposing rats to 10 cGy of 56Fe particles attenuated amphetamine-induced taste aversion learning. This behavior is one of a broad class of behaviors which depends on the integrity of the dopaminergic system and suggests the possibility of alterations in these behaviors following exposure to heavy particles in a space radiation environment.

  5. Delay in surgery predisposes to meniscal and chondral injuries in anterior cruciate ligament deficient knees

    PubMed Central

    Gupta, Ravi; Masih, Gladson David; Chander, Gaurav; Bachhal, Vikas

    2016-01-01

    Background: Despite improvements in instability after anterior cruciate ligament (ACL) reconstruction, associated intraarticular injuries remain a major cause of concern and important prognostic factor for long term results as it may lead to osteoarthritis. Delay in ACL reconstruction has been in variably linked to increase in these injuries but there is lack of consensus regarding optimal timing of reconstruction. The goal of this study was to investigate delay in surgery and other factors, associated with intraarticular injuries in ACL deficient knees. Materials and Methods: A total of 438 patients (42 females; 396 males) enrolled for this prospective observational study. The average age of patients was 26.43 (range 17–51 years) years with a mean surgical delay of 78.91 (range 1 week - 18 years) weeks after injury. We analyzed the factors of age, sex, surgical delay, instability, and level of activity for possible association with intraarticular injuries. Results: Medial meniscus injuries had a significant association with surgical delay (P = 0.000) after a delay of 6 months. Lateral meniscus injuries had a significant association with degree of instability (P = 0.001). Medial-sided articular injuries were significantly affected by age (0.005) with an odds ratio (OR) of 1.048 (95% confidence interval [CI] of 1.014–1.082) reflecting 4.8% rise in incidence with each year. Lateral-sided injuries were associated with female sex (P = 0.018) with OR of 2.846 (95% CI of 1.200–6.752). The level of activity failed to reveal any significant associations. Conclusion: Surgical delay predicts an increase in medial meniscal and lateral articular injuries justifying early rather than delayed reconstruction in ACL deficient knees. Increasing age is positively related to intraarticular injuries while females are more susceptible to lateral articular injuries. PMID:27746491

  6. Management of ionizing radiation injuries and illnesses, part 1: physics, radiation protection, and radiation instrumentation.

    PubMed

    Christensen, Doran M; Jenkins, Mark S; Sugarman, Stephen L; Glassman, Erik S

    2014-03-01

    Ionizing radiation injuries and illnesses are exceedingly rare; therefore, most physicians have never managed such conditions. When confronted with a possible radiation injury or illness, most physicians must seek specialty consultation. Protection of responders, health care workers, and patients is an absolute priority for the delivery of medical care. Management of ionizing radiation injuries and illnesses, as well as radiation protection, requires a basic understanding of physics. Also, to provide a greater measure of safety when working with radioactive materials, instrumentation for detection and identification of radiation is needed. Because any health care professional could face a radiation emergency, it is imperative that all institutions have emergency response plans in place before an incident occurs. The present article is an introduction to basic physics, ionizing radiation, radiation protection, and radiation instrumentation, and it provides a basis for management of the consequences of a radiologic or nuclear incident.

  7. Longitudinal Assessment of Stereotypic, Proto-Injurious, and Self-Injurious Behavior Exhibited by Young Children with Developmental Delays

    ERIC Educational Resources Information Center

    Richman, David M.; Lindauer, Steven E.

    2005-01-01

    Twelve children (CA, 12 to 32 months) with developmental delay were observed in their homes during monthly analogue functional analysis probes to document patterns of emerging self-injurious behavior. Two patterns of emerging self-injury were observed for 5 participants: (a) The topography and functional analysis pattern remained the same, but the…

  8. Immune System Phenotyping of Radiation and Radiation Combined Injury in Outbred Mice

    PubMed Central

    Tajima, G.; Delisle, A. J.; Hoang, K.; O’Leary, F. M.; Ikeda, K.; Hanschen, M.; Stoecklein, V. M.; Lederer, J. A.

    2014-01-01

    The complexity of a radionuclear event would be immense due to varying levels of radiation exposures and injuries caused by blast-associated trauma. With this scenario in mind, we developed a mouse model to mimic as closely as possible the potential consequences of radiation injury and radiation combined injury (RCI) on survival, immune system phenotype, and immune function. Using a mouse burn injury model and a 137CsCl source irradiator to induce injuries, we report that the immunological response to radiation combined injury differs significantly from radiation or burn injury alone. Mice that underwent radiation combined injury showed lower injury survival and cecal ligation and puncture (CLP) induced polymicrobial sepsis survival rates than mice with single injuries. As anticipated, radiation exposure caused dose-dependent losses of immune cell subsets. We found B and T cells to be more radiation sensitive, while macrophages, dendritic cells and NK cells were relatively more resistant. However, radiation and radiation combined injury did induce significant increases in the percentages of CD4+ regulatory T cells (Tregs) and a subset of macrophages that express cell-surface GR-1 (GR-1+ macrophages). Immune system phenotyping analysis indicated that spleen cells from radiation combined injury mice produced higher levels of proinflammatory cytokines than cells from mice with radiation or burn injury alone, especially at lower dose radiation exposure levels. Interestingly, this enhanced proinflammatory phenotype induced by radiation combined injury persisted for at least 28 days after injury. In total, our data provide baseline information on differences in immune phenotype and function between radiation injury and radiation combined injury in mice. The establishment of this animal model will aid in future testing for therapeutic strategies to mitigate the immune and pathophysiological consequences of radionuclear events. PMID:23216446

  9. Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

    PubMed Central

    Pluta, Ryszard M.; Zhang, John H.

    2010-01-01

    Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are identified. In addition, it is found that many of these mechanisms evolve with time and participate in the pathogenesis of delayed ischemic injury and poor outcome. Therefore, a therapy or therapies focused on these early mechanisms may not only prevent the early brain injury but may also help reduce the intensity of later developing neurological complications. This manuscript reviews the pathological mechanisms of early brain injury after SAH and summarizes the status of current therapies. PMID:21161614

  10. Evidence for factors modulating radiation-induced G2-delay: potential application as radioprotectors

    NASA Technical Reports Server (NTRS)

    Cheong, N.; Zeng, Z. C.; Wang, Y.; Iliakis, G.

    2001-01-01

    Manipulation of checkpoint response to DNA damage can be developed as a means for protecting astronauts from the adverse effects of unexpected, or background exposures to ionizing radiation. To achieve this goal reagents need to be developed that protect cells from radiation injury by prolonging checkpoint response, thus promoting repair. We present evidence for a low molecular weight substance excreted by cells that dramatically increases the duration of the G2-delay. This compound is termed G2-Arrest Modulating Activity (GAMA). A rat cell line (A1-5) generated by transforming rat embryo fibroblasts with a temperature sensitive form of p53 plus H-ras demonstrates a dramatic increase in radiation resistance after exposure to low LET radiation that is not associated with an increase in the efficiency of rejoining of DNA double strand breaks. Radioresistance in this cell line correlates with a dramatic increase in the duration of the G2 arrest that is modulated by a GAMA produced by actively growing cells. The properties of GAMA suggest that it is a low molecular weight heat-stable peptide. Further characterization of this substance and elucidation of its mechanism of action may allow the development of a biological response modifier with potential applications as a radioprotector. GAMA may be useful for protecting astronauts from radiation injury as preliminary evidence suggests that it is able to modulate the response of cells exposed to heavy ion radiation, similar to that encountered in outer space.

  11. Radiation-induced brain injury: A review

    PubMed Central

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  12. Delayed effects of ionizing radiation on the ear

    SciTech Connect

    Bohne, B.A.; Marks, J.E.; Glasgow, G.P.

    1985-07-01

    The question of damage to the ear from exposure to ionizing radiation was addressed by exposing groups of chinchillas to fractioned doses of radiation (2 Gy per day) for total doses ranging from 40 to 90 Gy. In order to allow any delayed effects of radiation to become manifest, the animals were sacrificed two years after completion of treatment and their temporal bones were prepared for microscopic examination. The most pronounced effect of treatment was degeneration of sensory and supporting cells and loss of eighth nerve fibers in the organ of Corti. Damage increased with increasing dose of radiation. The degree of damage found in many of these ears was of sufficient magnitude to produce a permanent sensorineural hearing loss.

  13. Evaluation of delayed effects of ionizing radiation: an historical perspective.

    PubMed

    Stewart, A M

    1991-01-01

    It is widely assumed that after the bombing of Hiroshima and Nagasaki there were no lasting effects of the acute injuries (which included extensive damage to blood forming tissues by the radiation) or the massively high death rate (which was caused by environmental effects of the blast as well as personal injuries). However, close inspection of the dose response curves for non-cancer deaths has shown that this could be a false impression caused by one effect of marrow aplasia being confused with leukemia (defective erythropoiesis) and a second effect being confused with early selection in favor of general fitness (defective immune responses). Possible consequences of such confusion (for cancer risk coefficients) are discussed in relation to what is known about late effects of prenatal x-rays and occupational exposures to radiation. PMID:1805618

  14. Protective effects of batimastat against hemorrhagic injuries in delayed jellyfish envenomation syndrome models.

    PubMed

    Wang, Beilei; Liu, Dan; Liu, Guoyan; Zhang, Xin; Wang, Qianqian; Zheng, Jiemin; Zhou, Yonghong; He, Qian; Zhang, Liming

    2015-12-15

    Previously, we established delayed jellyfish envenomation syndrome (DJES) models and proposed that the hemorrhagic toxins in jellyfish tentacle extracts (TE) play a significant role in the liver and kidney injuries of the experimental model. Further, we also demonstrated that metalloproteinases are the central toxic components of the jellyfish Cyanea capillata (C. capillata), which may be responsible for the hemorrhagic effects. Thus, metalloproteinase inhibitors appear to be a promising therapeutic alternative for the treatment of hemorrhagic injuries in DJES. In this study, we examined the metalloproteinase activity of TE from the jellyfish C. capillata using zymography analyses. Our results confirmed that TE possessed a metalloproteinase activity, which was also sensitive to heat. Then, we tested the effect of metalloproteinase inhibitor batimastat (BB-94) on TE-induced hemorrhagic injuries in DJES models. Firstly, using SR-based X-ray microangiography, we found that BB-94 significantly improved TE-induced hepatic and renal microvasculature alterations in DJES mouse model. Secondly, under synchrotron radiation micro-computed tomography (SR-μCT), we also confirmed that BB-94 reduced TE-induced hepatic and renal microvasculature changes in DJES rat model. In addition, being consistent with the imaging results, histopathological and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL)-like staining observations also clearly corroborated this hypothesis, as BB-94 was highly effective in neutralizing TE-induced extensive hemorrhage and necrosis in DJES rat model. Although it may require further clinical studies in the near future, the current study opens up the possibilities for the use of the metalloproteinase inhibitor, BB-94, in the treatment of multiple organ hemorrhagic injuries in DJES.

  15. Integrative Metabolic Signatures for Hepatic Radiation Injury

    PubMed Central

    Su, Gang; Meng, Fan; Liu, Laibin; Mohney, Robert; Kulkarni, Shilpa; Guha, Chandan

    2015-01-01

    Background Radiation-induced liver disease (RILD) is a dose-limiting factor in curative radiation therapy (RT) for liver cancers, making early detection of radiation-associated liver injury absolutely essential for medical intervention. A metabolomic approach was used to determine metabolic signatures that could serve as biomarkers for early detection of RILD in mice. Methods Anesthetized C57BL/6 mice received 0, 10 or 50 Gy Whole Liver Irradiation (WLI) and were contrasted to mice, which received 10 Gy whole body irradiation (WBI). Liver and plasma samples were collected at 24 hours after irradiation. The samples were processed using Gas Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry. Results Twenty four hours after WLI, 407 metabolites were detected in liver samples while 347 metabolites were detected in plasma. Plasma metabolites associated with 50 Gy WLI included several amino acids, purine and pyrimidine metabolites, microbial metabolites, and most prominently bradykinin and 3-indoxyl-sulfate. Liver metabolites associated with 50 Gy WLI included pentose phosphate, purine, and pyrimidine metabolites in liver. Plasma biomarkers in common between WLI and WBI were enriched in microbial metabolites such as 3 indoxyl sulfate, indole-3-lactic acid, phenyllactic acid, pipecolic acid, hippuric acid, and markers of DNA damage such as 2-deoxyuridine. Metabolites associated with tryptophan and indoles may reflect radiation-induced gut microbiome effects. Predominant liver biomarkers in common between WBI and WLI were amino acids, sugars, TCA metabolites (fumarate), fatty acids (lineolate, n-hexadecanoic acid) and DNA damage markers (uridine). Conclusions We identified a set of metabolomic markers that may prove useful as plasma biomarkers of RILD and WBI. Pathway analysis also suggested that the unique metabolic changes observed after liver irradiation was an integrative response of the intestine, liver and kidney. PMID:26046990

  16. Traumatic brain injury causes delayed motor and cognitive impairment in a mutant mouse strain known to exhibit delayed Wallerian degeneration.

    PubMed

    Fox, G B; Faden, A I

    1998-09-15

    Delayed Wallerian degeneration after neuronal injury is a feature of the C57BL/Wld(s) mouse mutant. In the present study, we examined the effect of unilateral controlled cortical impact (CCI) on motor and cognitive performance in C57BL/6 and C57BL/Wld(s) mice. Performance on a beam-walking task was impaired in both injured groups over the first 3 weeks; however, between 28 and 35 days post injury, C57BL/6 mice continued to improve whereas C57BL/Wld(s) mice showed increased footfaults. In a spatial learning task, C57BL/Wld(s) animals performed consistently better than C57BL/6 mice when tested 7-10 days and 14-17 days following CCI. C57BL/Wld(s) mice also demonstrated improved working memory performance as compared with C57BL/6 mice when trained on days 21-22 after injury; this effect was lost on days 23 and 24, and was not evident in other animals tested in the same task at 28-31 days following injury. These results indicate a marked delay in motor and cognitive impairment following CCI in C57BL/Wld(s) mice compared with injured C57BL/6 controls. This is consistent with previous work showing delayed temporal evolution of neuronal degeneration in C57BL/Wld(s) mice and suggests CCI may be a suitable model for examining the functional consequences of traumatic brain injury (TBI) in genetically altered mice.

  17. Hematocolpos as a Result of Delayed Treatment of Acute Straddle Injury in an Adolescent Girl.

    PubMed

    Hwang, Hae Jin; Lim, Hyun Wook; Han, Young Shin; Choi, Jeong In; Kim, Min Jeong

    2016-01-01

    Accidental genital trauma is most commonly caused by straddle-type injuries and is usually treatable by nonoperative management, and most of the injuries have a good prognosis. When the bleeding occurred due to straddle injury in adolescent girl, experienced gynecological examination and treatment were very important. We experienced a case of straddle injury to the posterior fourchette that caused acute hematocolpos due to delayed adequate treatment with hypotension and acute abdomen in an adolescent girl. This case shows the importance of careful and accurate physical and gynecological examination and adequate and prompt treatment of genital trauma in adolescent girls.

  18. Mechanisms of Hypothermia, Delayed Hyperthermia and Fever Following CNS Injury

    EPA Science Inventory

    Central nervous system (CNS) damage is often associated with robust body temperature changes, such as hypothermia and delayed hyperthermia. Hypothermia is one of the most common body temperature changes to CNS insults in rodents and is often associated with improved outcome. Alth...

  19. UVB Radiation Delays Tribolium castaneum Metamorphosis by Influencing Ecdysteroid Metabolism

    PubMed Central

    Sang, Wen; Yu, Lin; He, Li; Ma, Wei-Hua; Zhu, Zhi-Hui; Zhu, Fen; Wang, Xiao-Ping; Lei, Chao-Liang

    2016-01-01

    Ultraviolet B (UVB) radiation is an important environmental factor. It is generally known that UVB exhibits high genotoxicity due to causing DNA damage, potentially leading to skin carcinogenesis and aging in mammals. However, little is known about the effects of UVB on the development and metamorphosis of insects, which are the most abundant terrestrial animals. In the present study, we performed dose-response analyses of the effects UVB irradiation on Tribolium castaneum metamorphosis, assessed the function of the T. castaneum prothoracicotropic hormone gene (Trcptth), and analyzed ecdysteroid pathway gene expression profile and ecdysterone titers post-UVB irradiation. The results showed that UVB not only caused death of T. castaneum larvae, but also delayed larval-pupal metamorphosis and reduced the size and emergence rate of pupae. In addition, we verified the function of Trcptth, which is responsible for regulating metamorphosis. It was also found that the expression profiles of Trcptth as well as ecdysteroidogenesis and response genes were influenced by UVB radiation. Therefore, a disturbance pulse of ecdysteroid may be involved in delaying development under exposure to irradiation. To our knowledge, this is the first report indicating that UVB can influence the metamorphosis of insects. This study will contribute to a better understanding of the impact of UVB on signaling mechanisms in insect metamorphosis. PMID:26986217

  20. UVB Radiation Delays Tribolium castaneum Metamorphosis by Influencing Ecdysteroid Metabolism.

    PubMed

    Sang, Wen; Yu, Lin; He, Li; Ma, Wei-Hua; Zhu, Zhi-Hui; Zhu, Fen; Wang, Xiao-Ping; Lei, Chao-Liang

    2016-01-01

    Ultraviolet B (UVB) radiation is an important environmental factor. It is generally known that UVB exhibits high genotoxicity due to causing DNA damage, potentially leading to skin carcinogenesis and aging in mammals. However, little is known about the effects of UVB on the development and metamorphosis of insects, which are the most abundant terrestrial animals. In the present study, we performed dose-response analyses of the effects UVB irradiation on Tribolium castaneum metamorphosis, assessed the function of the T. castaneum prothoracicotropic hormone gene (Trcptth), and analyzed ecdysteroid pathway gene expression profile and ecdysterone titers post-UVB irradiation. The results showed that UVB not only caused death of T. castaneum larvae, but also delayed larval-pupal metamorphosis and reduced the size and emergence rate of pupae. In addition, we verified the function of Trcptth, which is responsible for regulating metamorphosis. It was also found that the expression profiles of Trcptth as well as ecdysteroidogenesis and response genes were influenced by UVB radiation. Therefore, a disturbance pulse of ecdysteroid may be involved in delaying development under exposure to irradiation. To our knowledge, this is the first report indicating that UVB can influence the metamorphosis of insects. This study will contribute to a better understanding of the impact of UVB on signaling mechanisms in insect metamorphosis.

  1. UVB Radiation Delays Tribolium castaneum Metamorphosis by Influencing Ecdysteroid Metabolism.

    PubMed

    Sang, Wen; Yu, Lin; He, Li; Ma, Wei-Hua; Zhu, Zhi-Hui; Zhu, Fen; Wang, Xiao-Ping; Lei, Chao-Liang

    2016-01-01

    Ultraviolet B (UVB) radiation is an important environmental factor. It is generally known that UVB exhibits high genotoxicity due to causing DNA damage, potentially leading to skin carcinogenesis and aging in mammals. However, little is known about the effects of UVB on the development and metamorphosis of insects, which are the most abundant terrestrial animals. In the present study, we performed dose-response analyses of the effects UVB irradiation on Tribolium castaneum metamorphosis, assessed the function of the T. castaneum prothoracicotropic hormone gene (Trcptth), and analyzed ecdysteroid pathway gene expression profile and ecdysterone titers post-UVB irradiation. The results showed that UVB not only caused death of T. castaneum larvae, but also delayed larval-pupal metamorphosis and reduced the size and emergence rate of pupae. In addition, we verified the function of Trcptth, which is responsible for regulating metamorphosis. It was also found that the expression profiles of Trcptth as well as ecdysteroidogenesis and response genes were influenced by UVB radiation. Therefore, a disturbance pulse of ecdysteroid may be involved in delaying development under exposure to irradiation. To our knowledge, this is the first report indicating that UVB can influence the metamorphosis of insects. This study will contribute to a better understanding of the impact of UVB on signaling mechanisms in insect metamorphosis. PMID:26986217

  2. Severe progressive periodontal destruction due to radiation tissue injury.

    PubMed

    Yusof, Z W; Bakri, M M

    1993-12-01

    Cancer radiotherapy to the head and neck region results in short- and long-term radiation tissue injuries. Radiation bone injury is a long-term manifestation which could progress to osteoradionecrosis. A case of radiation tissue injury to the periodontium is presented. The possible pathogenesis of these events is described as they relate to the sequential radiographic changes observed over a period of 6 years until the involved teeth were exfoliated. The post-irradiation management of the teeth with advancing periodontal disease in the path of irradiation was by conservative means, including good personal oral hygiene care, scaling and root planing, periodic chlorhexidine irrigation, and topical fluoride application.

  3. Delayed repair of lip avulsion following gun-shot injury--a case report.

    PubMed

    Adeosun, O O; Olasoji, H O

    2001-01-01

    A case of delayed repair of lower lip repair tissue avulsion following gun shot injury in a 35 year old commercial driver is presented. The report illustrates the need for adequate wound debridement over a period of time to demarcate viable tissues before surgical reconstruction. It also serves as a reminder of the problems that may be faced in managing facial gun shot injuries in the civilian population in our environment. PMID:11806017

  4. Impact of an angiotensin analogue in treating thermal and combined radiation injuries

    NASA Astrophysics Data System (ADS)

    Jadhav, Sachin Suresh

    Background: In recent years there has been a growing concern regarding the use of nuclear weapons by terrorists. Such incidents in the past have shown that radiation exposure is often accompanied by other forms of trauma such as burns, wounds or infection; leading to increased mortality rates among the affected individuals. This increased risk with combined radiation injury has been attributed to the delayed wound healing observed in this injury. The Renin-Angiotensin System (RAS) has emerged as a critical regulator of wound healing. Angiotensin II (A-II) and Angiotensin (1-7) [A(1-7)] have been shown to accelerate the rate of wound healing in different animal models of cutaneous injury. Nor-Leu3-Angiotensin (1-7) [Nor-Leu3-A (1-7)], an analogue of A(1-7), is more efficient than both A-II and A(1-7) in its ability to improve wound healing and is currently in phase III clinical trials for the treatment of diabetic foot ulcers. Aims: The three main goals of this study were to; 1) Develop a combined radiation and burn injury (CRBI) model and a radiation-induced cutaneous injury model to study the pathophysiological effects of these injuries on dermal wound healing; 2) To treat thermal and CRBI injuries using Nor-Leu 3-A (1-7) and decipher the mechanism of action of this peptide and 3) Develop an in-vitro model of CRBI using dermal cells in order to study the effect of CRBI on individual cell types involved in wound healing. Results: CRBI results in delayed and exacerbated apoptosis, necrosis and inflammation in injured skin as compared to thermal injury by itself. Radiation-induced cutaneous injury shows a radiation-dose dependent increase in inflammation as well as a chronic inflammatory response in the higher radiation exposure groups. Nor-Leu3-A (1-7) can mitigate thermal and CRBI injuries by reducing inflammation, oxidative stress and DNA damage while increasing the rate of proliferation of dermal stem cells and re-epithelialization of injured skin. The in

  5. Delayed olfactory ensheathing cell transplants reduce nociception after dorsal root injury.

    PubMed

    Wu, Ann; Lauschke, Jenny L; Gorrie, Catherine A; Cameron, Nicholas; Hayward, Ian; Mackay-Sim, Alan; Waite, Phil M E

    2011-05-01

    Injury to cervical dorsal roots mimics the deafferentation component of brachial plexus injury in humans, with intractable neuropathic pain in the deafferented limb being a common consequence. Such lesions are generally not amenable to surgical repair. The use of olfactory ensheathing cells (OECs) for dorsal root repair, via acute transplantation, has been successful in several studies. From a clinical point of view, delayed transplantation of OECs would provide a more realistic timeframe for repair. In this study we investigated the effect of delayed OEC transplantation on functional recovery of skilled forepaw movements and amelioration of neuropathic pain, using a C7 and C8 dorsal root injury rat model previously established in our lab. We found that OEC transplantation to the dorsal horn 1 week after root injury effectively attenuated neuropathic disturbances associated with dorsal root injury, including spontaneous pain behavior, tactile allodynia and thermal hyperalgesia. The sensory controls of complex, goal-oriented skilled reaching and ladder walking, however, were not improved by delayed OEC transplantation. We did not detect any significant influence of transplanted OECs on injury-induced central reorganisation and afferent sprouting. The anti-nociceptive effect mediated by OEC transplants may therefore be explained by alternative mechanisms such as modification of inflammation and astrogliosis. The significant effect of OEC transplants in mitigating neuropathic pain may be clinically useful in intractable pain syndromes arising from deafferentation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair. PMID:20643129

  6. Advantages of delaying the onset of rehabilitative reaching training in rats with incomplete spinal cord injury.

    PubMed

    Krajacic, Aleksandra; Ghosh, Mousumi; Puentes, Rocio; Pearse, Damien D; Fouad, Karim

    2009-02-01

    We have previously reported that rehabilitative reaching training initiated 4 days following an incomplete cervical spinal cord injury (SCI) in adult rats promotes plasticity and task-specific recovery. This training, however, also resulted in impairments in an untrained task. Here we examined whether delaying the rehabilitative training following cervical SCI is still effective in promoting task-specific recovery, but circumvents impairments in an untrained task, comparable to what has been reported in stroke models. Therefore, reaching training for a period of 6 weeks was initiated at Day 12 following a cervical dorso-lateral quadrant lesion. Thereupon the rats' ability to reach and to walk on a horizontal ladder (i.e. the untrained task) was assessed, and 8 weeks post-injury cortical map changes were investigated through microstimulation. Further, we examined changes in phospho protein kinase A (pPKA) levels following an immediate and a delayed onset of reaching training in rats with cervical SCI. We found that delayed rehabilitative training was comparably effective as immediate training in promoting task-specific recovery and sprouting of injured axons. Importantly, delayed training did not impair the performance on horizontal ladder walking. Strikingly, only delayed reaching training restored cortical PKA levels that had dropped significantly over 2 weeks post-injury. Additionally, delayed training did not influence cortical map changes following injury, but decreased white matter damage. In conclusion, our results show that a short delay in the onset of training in a forelimb task significantly alters our outcome measures, which should be considered in future rehabilitative approaches. PMID:19222562

  7. Essential Metalloelement Chelates Facilitate Repair of Radiation Injury

    PubMed Central

    Soderberg, Lee S. F.; Chang, Louis W.; Walker, Richard B.

    2001-01-01

    Treatment with essential metalloelement (Cu, Fe, Mn, and Zn) chelates or combinations of them before and/or after radiation injury is a useful approach to overcoming radiation injury. No other agents are known to increase survival when they are used to treat after irradiation, in a radiorecovery treatment paradigm. These chelates may be useful in facilitating de novo syntheses of essential metalloelement-dependent enzymes required to repair radiation injury. Reports of radioprotection, which involves treatment before irradiation, with calcium-channel blockers, acyl Melatonin homologs, and substituted anilines, which may serve as chelating agents after biochemical modification in vivo, as well as Curcumin, which is a chelating agent, have been included in this review. These inclusions are intended to suggest additional approaches to combination treatments that may be useful in facilitating radiation recovery. These approaches to radioprotection and radiorecovery offer promise in facilitating recovery from radiation-induced injury experienced by patients undergoing radiotherapy for neoplastic disease and by individuals who experience environmental, occupational, or accidental exposure to ultraviolet, x-ray, or γ-ray radiation. Since there are no existing treatments of radiation-injury intended to facilitate tissue repair, studies of essential metalloelement chelates and combinations of them, as well as combinations of them with existing organic radioprotectants, seem worthwhile. PMID:18475999

  8. Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury

    SciTech Connect

    Li, Yonggang; Lein, Pamela J.; Liu, Cuimei; Bruun, Donald A.; Giulivi, Cecilia; Ford, Gregory D.; Tewolde, Teclemichael; Ross-Inta, Catherine; Ford, Byron D.

    2012-07-15

    Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylflurophosphate (DFP). Adult male Sprague–Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. -- Highlights: ► NRG-1 blocked DFP induced neuronal injury. ► NRG-1 did not protect against seizures in rats exposed to DFP. ► NRG-1 blocked apoptosis and oxidative stress in the brains of DFP-intoxicated rats. ► Administration of NRG-1 at 1 h after DFP injection prevented delayed neuronal injury.

  9. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  10. Longitudinal assessment of stereotypic, proto-injurious, and self-injurious behavior exhibited by young children with developmental delays.

    PubMed

    Richman, David M; Lindauer, Steven E

    2005-11-01

    Twelve children (CA, 12 to 32 months) with developmental delay were observed in their homes during monthly analogue functional analysis probes to document patterns of emerging self-injurious behavior. Two patterns of emerging self-injury were observed for 5 participants: (a) The topography and functional analysis pattern remained the same, but the behavior eventually caused tissue damage; or (b) a new topography emerged that was similar to an established stereotypic motor behavior. Functional analysis results were inconclusive for the majority of target behaviors across participants due to undifferentiated responding across conditions. One participant exhibited two topographies that appeared to become sensitive to positive reinforcement over time. Results are discussed in terms of implications for future research on early intervention and prevention of self-injury.

  11. Radiation injury of boron neutron capture therapy using mixed epithermal- and thermal neutron beams in patients with malignant glioma.

    PubMed

    Kageji, T; Nagahiro, S; Mizobuchi, Y; Toi, H; Nakagawa, Y; Kumada, H

    2004-11-01

    The purpose of this study was to clarify the radiation injury in acute or delayed stage after boron neutron capture therapy (BNCT) using mixed epithermal- and thermal neutron beams in patients with malignant glioma. Eighteen patients with malignant glioma underwent mixed epithermal- and thermal neutron beam and sodium borocaptate between 1998 and 2004. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the protocol used between 1998 and 2000 (Protocol A, n = 8) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B, n = 4); it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to 6 glioblastoma patients (Protocol C, n = 6). The average values of the maximum vascular dose of brain surface in Protocol A, B and C were 11.4+/-4.2 Gy, 15.7+/-1.2 and 13.9+/-3.6 Gy, respectively. Acute radiation injury such as a generalized convulsion within 1 week after BNCT was recognized in three patients of Protocol B. Delayed radiation injury such as a neurological deterioration appeared 3-6 months after BNCT, and it was recognized in 1 patient in Protocol A, 5 patients in Protocol B. According to acute radiation injury, the maximum vascular dose was 15.8+/-1.3 Gy in positive and was 12.6+/-4.3 Gy in negative. There was no significant difference between them. According to the delayed radiation injury, the maximum vascular dose was 13.8+/-3.8 Gy in positive and was 13.6+/-4.9 Gy in negative. There was no significant difference between them. The dose escalation is limited because most patients in Protocol B suffered from acute radiation injury. We conclude that the maximum vascular dose does not exceed over 12 Gy to avoid the delayed radiation injury, especially, it should be limited under 10 Gy in the case that tumor

  12. Development and Characterization of VEGF165-Chitosan Nanoparticles for the Treatment of Radiation-Induced Skin Injury in Rats

    PubMed Central

    Yu, Daojiang; Li, Shan; Wang, Shuai; Li, Xiujie; Zhu, Minsheng; Huang, Shai; Sun, Li; Zhang, Yongsheng; Liu, Yanli; Wang, Shouli

    2016-01-01

    Radiation-induced skin injury, which remains a serious concern in radiation therapy, is currently believed to be the result of vascular endothelial cell injury and apoptosis. Here, we established a model of acute radiation-induced skin injury and compared the effect of different vascular growth factors on skin healing by observing the changes of microcirculation and cell apoptosis. Vascular endothelial growth factor (VEGF) was more effective at inhibiting apoptosis and preventing injury progression than other factors. A new strategy for improving the bioavailability of vascular growth factors was developed by loading VEGF with chitosan nanoparticles. The VEGF-chitosan nanoparticles showed a protective effect on vascular endothelial cells, improved the local microcirculation, and delayed the development of radioactive skin damage. PMID:27727163

  13. Development of a Combined Radiation and Burn Injury Model

    PubMed Central

    Palmer, Jessica L.; Deburghgraeve, Cory R.; Bird, Melanie D.; Hauer-Jensen, Martin; Kovacs, Elizabeth J.

    2011-01-01

    Combined radiation and burn injuries are likely to occur after nuclear events, such as a meltdown accident at a nuclear energy plant or a nuclear attack. Little is known about the mechanisms by which combined injuries result in higher mortality than by either insult alone, and few animal models exist for combined radiation and burn injury. Herein, the authors developed a murine model of radiation and scald burn injury. Mice were given a single dose of 0, 2, 4, 5, 6, or 9 Gray (Gy) alone, followed by a 15% TBSA scald burn. All mice receiving ≤4 Gy of radiation with burn survived combined injury. Higher doses of radiation (5, 6, and 9 Gy) followed by scald injury had a dose-dependent increase in mortality (34, 67, and 100%, respectively). Five Gy was determined to be the ideal dose to use in conjunction with burn injury for this model. There was a decrease in circulating white blood cells in burn, irradiated, and combined injury (5 Gy and burn) mice by 48 hours postinjury compared with sham (49.7, 11.6, and 57.3%, respectively). Circulating interleukin-6 and tumor necrosis factor-α were increased in combined injury at 48 hours postinjury compared with all other treatment groups. Prolonged overproduction of proinflammatory cytokines could contribute to subsequent organ damage. Decreased leukocytes might exacerbate immune impairment and susceptibility to infections. Future studies will determine whether there are long lasting consequences of this early proinflammatory response and extended decrease in leukocytes. (J Burn Care Res 2011;32:317–323) PMID:21233728

  14. Delayed effects of external radiation exposure: A brief history

    SciTech Connect

    Miller, R.W.

    1995-11-01

    Within months of Roentgen`s discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental retardation after their mothers had been given pelvic radiotherapy early in pregnancy. Fluoroscopy and radiotherapy for benign disorders continued to be used with abandon until authoritative reports were published on the adverse effects of ionizing radiation by the U.S. NAS-NRC and the UK MRC in 1956. Meanwhile, exposure to the atomic bombs in Japan had occurred and epidemics of delayed effects began to be recognized among the survivors: cataracts, leukemia and severe mental retardation among newborn infants after intra-uterine exposure. No statistically significant excess of germ-cell genetic effects was detected by six clinical measurements, the F{sub 1} mortality, cytogenetic studies or biochemical genetic studies. Somatic cell effects were revealed by long-lasting chromosomal aberrations in peripheral lymphocytes, and somatic cell mutations were found at the glycophorin A locus in erythrocytes. Molecular biology is a likely focus of new studies based on the function of the gene for ataxia telangiectasia, a disorder in which children have severe, even lethal acute radiation reactions when given conventional doses of radiotherapy for lymphoma, to which they are prone. The tumor registries in Hiroshima and Nagasaki now provide incidence data that show the extent of increases in eight common cancers and no increase in eight others. The possibility of very late effects of A-bomb exposure is suggested by recent reports of increased frequencies of hyperparathyroidism, parathyroid cancers and certain causes of death other than cancer. 88 refs., 1 fig.

  15. Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

    PubMed

    Choi, Iee Ho; Hwang, Pyoung Han; Choi, Sam Im; Lee, Dae Yeol; Kim, Min Sun

    2016-09-01

    Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas. PMID:27510397

  16. Activation of Protease Activated Receptor 2 by Exogenous Agonist Exacerbates Early Radiation Injury in Rat Intestine

    SciTech Connect

    Wang Junru; Boerma, Marjan; Kulkarni, Ashwini; Hollenberg, Morley D.; Hauer-Jensen, Martin

    2010-07-15

    Purpose: Protease-activated receptor-2 (PAR{sub 2}) is highly expressed throughout the gut and regulates the inflammatory, mitogenic, fibroproliferative, and nociceptive responses to injury. PAR{sub 2} is strikingly upregulated and exhibits increased activation in response to intestinal irradiation. We examined the mechanistic significance of radiation enteropathy development by assessing the effect of exogenous PAR{sub 2} activation. Methods and Materials: Rat small bowel was exposed to localized single-dose radiation (16.5 Gy). The PAR{sub 2} agonist (2-furoyl-LIGRLO-NH{sub 2}) or vehicle was injected intraperitoneally daily for 3 days before irradiation (before), for 7 days after irradiation (after), or both 3 days before and 7 days after irradiation (before-after). Early and delayed radiation enteropathy was assessed at 2 and 26 weeks after irradiation using quantitative histologic examination, morphometry, and immunohistochemical analysis. Results: The PAR{sub 2} agonist did not elicit changes in the unirradiated (shielded) intestine. In contrast, in the irradiated intestine procured 2 weeks after irradiation, administration of the PAR{sub 2} agonist was associated with more severe mucosal injury and increased intestinal wall thickness in all three treatment groups (p <.05) compared with the vehicle-treated controls. The PAR{sub 2} agonist also exacerbated the radiation injury score, serosal thickening, and mucosal inflammation (p <.05) in the before and before-after groups. The short-term exogenous activation of PAR{sub 2} did not affect radiation-induced intestinal injury at 26 weeks. Conclusion: The results of the present study support a role for PAR{sub 2} activation in the pathogenesis of early radiation-induced intestinal injury. Pharmacologic PAR{sub 2} antagonists might have the potential to reduce the intestinal side effects of radiotherapy and/or as countermeasures in radiologic accidents or terrorism scenarios.

  17. Interleukin-18 delays neutrophil apoptosis following alcohol intoxication and burn injury.

    PubMed

    Akhtar, Suhail; Li, Xiaoling; Kovacs, Elizabeth J; Gamelli, Richard L; Choudhry, Mashkoor A

    2011-01-01

    Studies have shown that burn patients who are intoxicated at the time of injury are more susceptible to infection and have a higher incidence of mortality. A major cause of death in burn and trauma patients regardless of their alcohol (EtOH) exposure is multiple organ dysfunction, which is driven in part by the systemic inflammatory response and activated neutrophils. Neutrophils are short lived and undergo apoptosis to maintain homeostasis and resolution of inflammation. A delay in apoptosis of neutrophils is one important mechanism which allows for their prolonged presence and the release of potentially harmful enzymes. The purpose of this study was to examine whether EtOH intoxication combined with burn injury influences neutrophil apoptosis and whether IL-18 plays any role in this setting. To accomplish this investigation, rats were gavaged with EtOH (3.2 g/kg) 4 h before being subjected to sham or burn injury of ~12.5% of the total body surface area, and then killed on d 1 after injury. Peripheral blood neutrophils were isolated and lysed. The lysates were analyzed for pro- and antiapoptotic proteins. We found that EtOH combined with burn injury prolonged neutrophil survival. This prolonged neutrophil survival was accompanied by a decrease in the levels of the neutrophil proapoptotic protein Bax, and an increase in antiapoptotic proteins Mcl-1 and Bcl-xl. Administration of IL-18 antibody following burn injury normalized the levels of Bax, Mcl-1 and Bcl-xl. The decrease in caspase-3 and DNA fragmentation observed following EtOH and burn injury was also normalized in rats treated with anti-IL-18 antibody. These findings suggest that IL-18 delays neutrophil apoptosis following EtOH and burn injury by modulating the pro- and antiapoptotic proteins.

  18. Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    Key words: Cerebrovascular Acute Radiation Syndrome (Cv ARS), Radiation Neurotoxins (RNT), Neurotransmitters, Radiation Countermeasures, Antiradiation Vaccine (ArV), Antiradiation Blocking Antibodies, Antiradiation Antidote. Psychoneuroimmunology, Neurotoxicity. ABSTRACT: To review the role of Radiation Neurotoxins in triggering, developing of radiation induced central nervous system injury. Radiation Neurotoxins - rapidly acting blood toxic lethal agent, which activated after irradiation and concentrated, circulated in interstitial fluid, lymph, blood with interactions with cell membranes, receptors and cell compartments. Radiation Neurotoxins - biological molecules with high enzymatic activity and/or specific lipids and activated or modified after irradiation. The Radiation Neurotoxins induce increased permeability of blood vessels, disruption of the blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier and developing severe disorder of blood macro- and micro-circulation. Principles of Radiation Psychoneuro-immunology and Psychoneuro-allergology were applied for determination of pathological processes developed after irradiation or selective administration of Radiation Neurotoxins to radiation naïve mammals. Effects of radiation and exposure to radiation can develop severe irreversible abnormalities of Central Nervous System, brain structures and functions. Antiradiation Vaccine - most effective, advanced methods of protection, prevention, mitigation and treatment and was used for of Acute Radiation Syndromes and elaboration of new technology for immune-prophylaxis and immune-protection against ϒ, Heavy Ion, Neutron irradiation. Results of experiments suggested that blocking, antitoxic, antiradiation antibodies can significantly reduce toxicity of Radiation Toxins. New advanced technology include active immune-prophylaxis with Antiradiation Vaccine and Antiradiation therapy that included specific blocking antibodies to Radiation Neurotoxins

  19. Vascular hyper-reactivity following arterial balloon injury: distant and delayed effects.

    PubMed

    Wilson, Andrew J

    2004-05-01

    The adverse functional effects of balloon angioplasty include simple procedure failure, compromise of vessel lumen (rupture), and restenosis. A much less well-defined repercussion of balloon injury to arteries is a paradoxical alteration in vascular reactivity at an anatomically distant site. The paper by Accorsi-Mendonça in the current issue presents new data showing that, following balloon injury to the rat left common carotid artery, there is a delayed hyperreactivity to both phenylephrine and angiotensin II in the contralateral artery. The pharmacological basis of these effects is unknown, although the authors demonstrate that products of cyclooxygenase (COX) 1 or 2 are responsible for the hyperreactivity to angiotensin II and phenylephrine, respectively. The absence of delayed hyperreactivity to these agents in the aorta of injured rats would suggest that a humoral factor is not involved.

  20. Ureteral Injury with Delayed Massive Hematuria after Transvaginal Ultrasound-Guided Oocyte Retrieval.

    PubMed

    Burnik Papler, Tanja; Vrtačnik Bokal, Eda; Šalamun, Vesna; Galič, Dejan; Smrkolj, Tomaž; Jančar, Nina

    2015-01-01

    We report a case of ureteral injury with delayed hematuria after transvaginal oocyte retrieval. A 28-year-old infertile patient with a history of previous laparoscopic resection of endometriotic nodes of both sacrouterine ligaments presented with abdominal pain one day after oocyte retrieval. Four days after oocyte retrieval, she presented with massive hematuria that reappeared 6 days after oocyte retrieval. Monopolar coagulation with wire electrode and insertion of a double-J-stent was performed during operative cystoscopy. The patient recovered completely after transfusion and had no signs of renal impairment after ureteric stent removal. This is the first report of ureteral injury after oocyte retrieval presenting itself with delayed massive hematuria and no signs of renal dysfunction or urinary leakage into retroperitoneal space. PMID:26146577

  1. Ureteral Injury with Delayed Massive Hematuria after Transvaginal Ultrasound-Guided Oocyte Retrieval

    PubMed Central

    Burnik Papler, Tanja; Vrtačnik Bokal, Eda; Šalamun, Vesna; Galič, Dejan; Smrkolj, Tomaž; Jančar, Nina

    2015-01-01

    We report a case of ureteral injury with delayed hematuria after transvaginal oocyte retrieval. A 28-year-old infertile patient with a history of previous laparoscopic resection of endometriotic nodes of both sacrouterine ligaments presented with abdominal pain one day after oocyte retrieval. Four days after oocyte retrieval, she presented with massive hematuria that reappeared 6 days after oocyte retrieval. Monopolar coagulation with wire electrode and insertion of a double-J-stent was performed during operative cystoscopy. The patient recovered completely after transfusion and had no signs of renal impairment after ureteric stent removal. This is the first report of ureteral injury after oocyte retrieval presenting itself with delayed massive hematuria and no signs of renal dysfunction or urinary leakage into retroperitoneal space. PMID:26146577

  2. Effect of caffeine on radiation-induced mitotic delay: delayed expression of G/sub 2/ arrest

    SciTech Connect

    Rowley, R.; Zorch, M.; Leeper, D.B.

    1984-01-01

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G/sub 2/ cells progressed to mitosis in register and without arrest in G/sub 2/. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G/sub 2/ arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G/sub 2/ phases.

  3. Mechanisms of cardiac radiation injury and potential preventive approaches.

    PubMed

    Slezak, Jan; Kura, Branislav; Ravingerová, Táňa; Tribulova, Narcisa; Okruhlicova, Ludmila; Barancik, Miroslav

    2015-09-01

    In addition to cytostatic treatment and surgery, the most common cancer treatment is gamma radiation. Despite sophisticated radiological techniques however, in addition to irradiation of the tumor, irradiation of the surrounding healthy tissue also takes place, which results in various side-effects, depending on the absorbed dose of radiation. Radiation either damages the cell DNA directly, or indirectly via the formation of oxygen radicals that in addition to the DNA damage, react with all cell organelles and interfere with their molecular mechanisms. The main features of radiation injury besides DNA damage is inflammation and increased expression of pro-inflammatory genes and cytokines. Endothelial damage and dysfunction of capillaries and small blood vessels plays a particularly important role in radiation injury. This review is focused on summarizing the currently available data concerning the mechanisms of radiation injury, as well as the effectiveness of various antioxidants, anti-inflammatory cytokines, and cytoprotective substances that may be utilized in preventing, mitigating, or treating the toxic effects of ionizing radiation on the heart. PMID:26030720

  4. Telomerase deficiency delays renal recovery in mice after ischemia reperfusion injury by impairing autophagy

    PubMed Central

    Cheng, Huifang; Fan, Xiaofeng; Lawson, William E.; Paueksakon, Paisit; Harris, Raymond C.

    2015-01-01

    The aged population suffers increased morbidity and higher mortality in response to episodes of acute kidney injury (AKI). Aging is associated with telomere shortening, and both telomerase reverse transcriptase (TerT) and RNA (TerC) are essential to maintain telomere length. To define a role of telomerase deficiency in susceptibility to AKI, we used ischemia/reperfusion injury in wild type mice or mice with either TerC or TerT deletion. Injury induced similar renal impairment at day 1 in each genotype, as assessed by azotemia, proteinuria, acute tubular injury score and apoptotic tubular epithelial cell index. However, either TerC or TerT knockout significantly delayed recovery compared to wild type mice. Electron microscopy showed increased autophagosome formation in renal tubular epithelial cells in wild type mice but a significant delay of their development in TerC and TerT knockout mice. There were also impeded increases in the expression of the autophagosome marker LC3 II, prolonged accumulation of the autophagosome protein P62, an increase of the cell cycle regulator p16, and greater activation of the mTOR pathway. The mTORC1 inhibitor, rapamycin, partially restored the ischemia/reperfusion-induced autophagy response, without a significant effect on either p16 induction or tubule epithelial cell proliferation. Thus, muting the maintenance of normal telomere length in mice impaired recovery from AKI, due to an increase in tubule cell senescence and impairment of mTOR-mediated autophagy. PMID:25760322

  5. Radiation combined with thermal injury induces immature myeloid cells.

    PubMed

    Mendoza, April Elizabeth; Neely, Crystal Judith; Charles, Anthony G; Kartchner, Laurel Briane; Brickey, Willie June; Khoury, Amal Lina; Sempowski, Gregory D; Ting, Jenny P Y; Cairns, Bruce A; Maile, Robert

    2012-11-01

    The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sublethal ionization radiation exposure combined with a full-thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a full-thickness contact burn of 20% total body surface area or sham procedure followed by a single whole-body dose of 5-Gy radiation. Serum, spleen, and peripheral lymph nodes were harvested at 3 and 14 days after injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated proinflammatory and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but were significantly elevated after burn alone and RCI at 14 days after injury. In contrast to the T-cell-suppressive nature of myeloid-derived suppressor cells found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in interferon γ and a decrease in interleukin 10. This is consistent with previous work in burn injury indicating that a myeloid-derived suppressor cell-like population increases innate immunity. Radiation combined injury results in the increase in distinct populations of Gr-1CD11b cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host.

  6. Electrical delay line multiplexing for pulsed mode radiation detectors

    NASA Astrophysics Data System (ADS)

    Vinke, Ruud; Yeom, Jung Yeol; Levin, Craig S.

    2015-04-01

    Medical imaging systems are composed of a large number of position sensitive radiation detectors to provide high resolution imaging. For example, whole-body Positron Emission Tomography (PET) systems are typically composed of thousands of scintillation crystal elements, which are coupled to photosensors. Thus, PET systems greatly benefit from methods to reduce the number of data acquisition channels, in order to reduce the system development cost and complexity. In this paper we present an electrical delay line multiplexing scheme that can significantly reduce the number of readout channels, while preserving the signal integrity required for good time resolution performance. We experimented with two 4 × 4 LYSO crystal arrays, with crystal elements having 3 mm × 3 mm × 5 mm and 3 mm × 3 mm × 20 mm dimensions, coupled to 16 Hamamatsu MPPC S10931-050P SiPM elements. Results show that each crystal could be accurately identified, even in the presence of scintillation light sharing and inter-crystal Compton scatter among neighboring crystal elements. The multiplexing configuration degraded the coincidence timing resolution from ∼243 ps FWHM to ∼272 ps FWHM when 16 SiPM signals were combined into a single channel for the 4 × 4 LYSO crystal array with 3 mm × 3 mm × 20 mm crystal element dimensions, in coincidence with a 3 mm × 3 mm × 5 mm LYSO crystal pixel. The method is flexible to allow multiplexing configurations across different block detectors, and is scalable to an entire ring of detectors.

  7. Delayed gamma radiation from lightning induced nuclear reactions

    NASA Astrophysics Data System (ADS)

    Greenfield, M. B.; Sakuma, K.; Ikeda, Y.; Kubo, K.

    2004-03-01

    An increase in atmospheric gamma radiation observed with NaI and Ge detectors positioned about 15 m above ground was observed following natural lightning near Tokyo, Japan [1]. Background subtracted gamma ray rates GRR following numerous lightning strokes observed since 2001 persisted for a few hours and subsequently decayed with a half-life of about 50 minutes. Using a 3x3 Ge detector, with 2 KeV resolution, positioned about 2 m from one of the NaI detectors increases in GRR were observed minutes after the onset of lightning with a delayed 50 min exponential decay. Although most of the increase in activity occured at less than a few 100 KeV, on July 11, 2003 a 1267 +/-2 KeV line was observed. Although the statistics of this event were poor, the appearance of this line with an exponential decay of 50 min half-life suggests the possibility that it may be due to 39Cl (1267 MeV; half-life = 55.5 min) via the 40Ar(gamma,p)39Cl, 40Ar(p,2p)39Cl and/or 40Ar(n,d)39Cl reactions. Observations of > 10 MeV gamma rays observed in NaI detectors within 10s of meters from and coincident with rocket-triggered lightning at the International Center for Lightning Research and Testing suggest that charged particles accelerated in intense electric fields associated with lightning give rise to photons with sufficient energy to initiate nuclear reactions [2]. Further work to explain the cause of this anomalous activity is underway using natural and triggered lightning. 1. M. B. Greenfield et al., Journal of Applied Physics 93 no. 3 (2003) pp 1839-184. 2. J. R. Dwyer et al., Science 299, (2003), pp 694-697 and recent communications

  8. Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

    SciTech Connect

    Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

    2010-08-01

    Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-{alpha}, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-{alpha}, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

  9. Early radiographic changes in radiation bone injury

    SciTech Connect

    Fujita, M.; Tanimoto, K.; Wada, T.

    1986-06-01

    A chronologic series of periapical radiographs was evaluated for the purpose of detecting damage to bone and tooth-supporting tissues in a patient receiving radiation therapy for a basal cell carcinoma of the mandibular gingiva. Widening of the periodontal space was one of the early radiographic changes observed. It is suggested, from the sequence of radiographic changes, that radiation-induced changed in the circulatory system of the bone might be primarily responsible for the resulting changes.

  10. Antioxidant mechanisms in radiation injury and radioprotection

    SciTech Connect

    Weiss, J.F.; Kumar, K.S.

    1988-01-01

    Oxygen is a very important factor in determining radiosensitivity because it enhances the damage to cellular components caused by ionizing radiation, although mechanisms involved in UV irradiation damage may overlap ionizing radiation effects. This paper emphasizes chemical protection against damage by ionizing radiation and predominantly against the effects of photons (and gamma radiation). It is possible that free radicals and their products induced by ionizing radiation can interact with reactive oxygen species formed during normal processes, such as superoxide and hydrogen peroxide produced by phagocytic cells or during enzymatic processes (xanthine oxidase activity; enzymes involved in eicosanoid metabolism). Metals such as iron can promote free radical damage, whereas some bound metals have radioprotectant potential, e.g., metallothionein and ceruloplasmin. There is increasing evidence that maintenance of the proper oxidation-reduction state of cells by the interconversion of the peptide sulfhydryl glutathione (GSH), and its disulfide form (GSSG) is a factor in the modulation of cellular radiosensitivity. Other protein and nonprotein sulfhydryls may also play a role both as targets of radiation damage and as protectors. Other physiological antioxidants (vitamin E) and antioxidant enzymes are interrelated in their function of controlling oxidative processes. This review concentrates on the role of oxygen, glutathione, and antioxidant enzymes in radiosensitivity and how exogenous chemicals interact with these endogenous factors.

  11. Reduced functional recovery by delaying motor training after spinal cord injury.

    PubMed

    Norrie, B A; Nevett-Duchcherer, J M; Gorassini, M A

    2005-07-01

    The purpose of this study was to examine if a delay in rehabilitative motor training after spinal cord injury affects functional motor recovery. We studied a skilled motor task in which rats traversed a raised horizontal ladder and we quantified errors in accurate stepping, i.e., foot slips between rungs. After lesions to the dorsal quadrant of the thoracic (T8) spinal cord that aimed to unilaterally sever the corticospinal and rubrospinal tracts, rats were re-trained to walk across the ladder, either immediately after injury or after a 3-mo delay. Before training, the error rate in accurate stepping of the affected hindlimb was similar in the immediately (69.4 +/- 5.3%) and delay (62.7 +/- 4.1%; means +/- SE)-trained animals (not significantly different), suggesting that accurate stepping did not improve spontaneously if rats were not exposed to the ladder. After a 3-wk course of training (30 runs across the ladder per day, 5 day/wk), improvements in accurate stepping performance were greater if training was implemented immediately after injury. On average, immediately trained animals improved stepping performance by 61.5 +/- 28.2%, whereas the delay trained group improved by only 34.9 +/- 28.8% (significantly different). The degree of damage to the corticospinal and rubrospinal tracts was very similar in the two groups of animals, indicating that differences in lesion size did not contribute to the differences in performance improvement. Animals with large lesions to the corticospinal and rubrospinal tracts (>70%) displayed poor recovery from training (especially for delay-trained animals), suggesting that these two pathways were important in mediating improvements in accurate stepping. In addition, recovery of stepping-like reflexes appeared not to contribute to the recovery of accurate stepping given that the time course of reflex recovery was not related to the time course of recovery of accurate stepping. We conclude that training of a skilled motor task that

  12. Delayed Presentation of Sciatic Nerve Injury after Total Hip Arthroplasty: Neurosurgical Considerations, Diagnosis, and Management

    PubMed Central

    Xu, Linda W.; Veeravagu, Anand; Azad, Tej D.; Harraher, Ciara; Ratliff, John K.

    2016-01-01

    Background  Total hip arthroplasty (THA) is an established treatment for end-stage arthritis, congenital deformity, and trauma with good long-term clinical and functional outcomes. Delayed sciatic nerve injury is a rare complication after THA that requires prompt diagnosis and management. Methods  We present a case of sciatic nerve motor and sensory deficit in a 52-year-old patient 2 years after index left THA. Electromyography (EMG) results and imaging with radiographs and CT of the affected hip demonstrated an aberrant acetabular cup screw in the posterior-inferior quadrant adjacent to the sciatic nerve. Case Description  The patient underwent surgical exploration that revealed injury to the peroneal division of the sciatic nerve due to direct injury from screw impingement. A literature review identified 11 patients with late-onset neuropathy after THA. Ten patients underwent surgical exploration and pain often resolved after surgery with 56% of patients recovering sensory function and 25% experiencing full recovery of motor function. Conclusions  Delayed neuropathy of the sciatic nerve is a rare complication after THA that is most often due to hardware irritation, component failure, or wear-related pseudotumor formation. Operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function. PMID:27602309

  13. Delayed Presentation of Sciatic Nerve Injury after Total Hip Arthroplasty: Neurosurgical Considerations, Diagnosis, and Management

    PubMed Central

    Xu, Linda W.; Veeravagu, Anand; Azad, Tej D.; Harraher, Ciara; Ratliff, John K.

    2016-01-01

    Background  Total hip arthroplasty (THA) is an established treatment for end-stage arthritis, congenital deformity, and trauma with good long-term clinical and functional outcomes. Delayed sciatic nerve injury is a rare complication after THA that requires prompt diagnosis and management. Methods  We present a case of sciatic nerve motor and sensory deficit in a 52-year-old patient 2 years after index left THA. Electromyography (EMG) results and imaging with radiographs and CT of the affected hip demonstrated an aberrant acetabular cup screw in the posterior-inferior quadrant adjacent to the sciatic nerve. Case Description  The patient underwent surgical exploration that revealed injury to the peroneal division of the sciatic nerve due to direct injury from screw impingement. A literature review identified 11 patients with late-onset neuropathy after THA. Ten patients underwent surgical exploration and pain often resolved after surgery with 56% of patients recovering sensory function and 25% experiencing full recovery of motor function. Conclusions  Delayed neuropathy of the sciatic nerve is a rare complication after THA that is most often due to hardware irritation, component failure, or wear-related pseudotumor formation. Operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function.

  14. Radiation injury to the temporal bone

    SciTech Connect

    Guida, R.A.; Finn, D.G.; Buchalter, I.H.; Brookler, K.H.; Kimmelman, C.P. )

    1990-01-01

    Osteoradionecrosis of the temporal bone is an unusual sequela of radiation therapy to the head and neck. Symptoms occur many years after the radiation is administered, and progression of the disease is insidious. Hearing loss (sensorineural, conductive, or mixed), otalgia, otorrhea, and even gross tissue extrusion herald this condition. Later, intracranial complications such as meningitis, temporal lobe or cerebellar abscess, and cranial neuropathies may occur. Reported here are five cases of this rare malady representing varying degrees of the disease process. They include a case of radiation-induced necrosis of the tympanic ring with persistent squamous debris in the external auditory canal and middle ear. Another case demonstrates the progression of radiation otitis media to mastoiditis with bony sequestration. Further progression of the disease process is seen in a third case that evolved into multiple cranial neuropathies from skull base destruction. Treatment includes systemic antibiotics, local wound care, and debridement in cases of localized tissue involvement. More extensive debridement with removal of sequestrations, abscess drainage, reconstruction with vascularized tissue from regional flaps, and mastoid obliteration may be warranted for severe cases. Hyperbaric oxygen therapy has provided limited benefit.

  15. Photosynthetically active radiation (PAR) x ultraviolet radiation (UV) interact to initiate solar injury in apple

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sunburn or solar injury (SI) in apple is associated with high temperature, high visible light and ultraviolet radiation (UV). Fruit surface temperature (FST) thresholds for SI related disorders have been developed but there are no thresholds established for solar radiation. The objectives of the s...

  16. Radiation-induced lung injury: a hypersensitivity pneumonitis

    SciTech Connect

    Gibson, P.G.; Bryant, D.H.; Morgan, G.W.; Yeates, M.; Fernandez, V.; Penny, R.; Breit, S.N.

    1988-08-15

    Radiation pneumonitis occurs 6 to 12 weeks after thoracic irradiation, and is thought to be due to direct radiation-induced lung injury. Four patients who developed pneumonitis after unilateral thoracic irradiation for carcinoma of the breast were studied with bronchoalveolar lavage, gallium scan of the lung, and respiratory function tests. On the irradiated side of the chest, all four patients showed an increase in total cells recovered from the lavage fluid and a marked increase in the percentage of lymphocytes. When results for the unirradiated lung were compared with results for the irradiated lung, there was a comparable increase in total cells and percentage of lymphocytes. Gallium scans showed increases for both irradiated and unirradiated lungs. Prompt improvement was seen after corticosteroid therapy in all patients. The fact that abnormal findings occur equally in irradiated and unirradiated lung is inconsistent with simple direct radiation-induced injury and suggests an immunologically mediated mechanism such as a hypersensitivity pneumonitis.

  17. [Ultrasonic diagnosis of radiation injuries of the urinary system].

    PubMed

    Mukhamedzhanov, I Kh; Kiseleva, M V; Kurpesheva, A K; Poltorakov, A M

    1991-01-01

    The paper is concerned with the results of ultrasound investigation of the kidneys and bladder in 78 patients with radiation injuries of pelvic tissues and organs. Comparison of the results of USI, isotope renography and excretory urography has shown that with an increase in the gravity of injury of the urinary system, the frequency of ultrasound findings rises from 60.8% in renal dysfunction of a mean gravity up to 91.2% in severe disorders. Echography data on the presence of hydronephrosis, pyelocaliectasis, a granular kidney, pyelonephritis, and nephroptosis usually coincided with the results of excretory urography in these patients. A combined use of echography and renography permits obtaining in most cases necessary data on structural and functional disorders of the urinary tracts. Echographic semiotics of radiation cystitis was studied in detail versus cystoscopy data. The informative value of ultrasound scanning of the bladder was observed in patients with radiation cystitis.

  18. Delayed Post-Injury Administration of Riluzole Is Neuroprotective in a Preclinical Rodent Model of Cervical Spinal Cord Injury

    PubMed Central

    Wu, Yongchao; Satkunendrarajah, Kajana; Teng, Yang; Chow, Diana S.-L.; Buttigieg, Josef

    2013-01-01

    Abstract Riluzole, a sodium/glutamate antagonist has shown promise as a neuroprotective agent. It is licensed for amyotrophic lateral sclerosis and is in clinical trial development for spinal cord injury (SCI). This study investigated the therapeutic time-window and pharmacokinetics of riluzole in a rodent model of cervical SCI. Rats were treated with riluzole (8 mg/kg) at 1 hour (P1) and 3 hours (P3) after injury or with vehicle. Afterward, P1 and P3 groups received riluzole (6 (mg/kg) every 12 hours for 7 days. Both P1 and P3 animals had significant improvements in locomotor recovery as measured by open field locomotion (BBB score, BBB subscore). Von Frey stimuli did not reveal an increase in at level or below level mechanical allodynia. Sensory-evoked potential recordings and quantification of axonal cytoskeleton demonstrated a riluzole-mediated improvement in axonal integrity and function. Histopathological and retrograde tracing studies demonstrated that delayed administration leads to tissue preservation and reduces apoptosis and inflammation. High performance liquid chromatography (HPLC) was undertaken to examine the pharmacokinetics of riluzole. Riluzole penetrates the spinal cord in 15 min, and SCI slowed elimination of riluzole from the spinal cord, resulting in a longer half-life and higher drug concentration in spinal cord and plasma. Initiation of riluzole treatment 1 and 3 hours post-SCI led to functional, histological, and molecular benefits. While extrapolation of post-injury time windows from rat to man is challenging, evidence from SCI-related biomarker studies would suggest that the post-injury time window is likely to be at least 12 hours in man. PMID:23517137

  19. Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation

    PubMed Central

    Liu, Yang; Wang, Jiazhong; Yang, Peng; Lu, Hongwei; Lu, Le; Wang, Jinlong; Li, Hua; Duan, Yanxia; Wang, Jun; Li, Yiming

    2015-01-01

    Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-β expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT. PMID:25406364

  20. Radiation Combined with Thermal Injury Induces Immature Myeloid Cells

    PubMed Central

    Mendoza, April Elizabeth; Neely, Crystal Judith; Charles, Anthony G.; Kartchner, Laurel Briane; Brickey, Willie June; Khoury, Amal Lina; Sempowski, Gregory D.; Ting, Jenny P.Y.; Cairns, Bruce A.; Maile, Robert

    2012-01-01

    The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sub-lethal ionization radiation exposure combined with a full thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a 20% total body surface area (TBSA) full-thickness contact burn or sham procedure followed by a single whole body dose of 5-Gy radiation. Serum, spleen and peripheral lymph nodes were harvested at 3 and 14 days post-injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated pro- and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but was significantly elevated after burn alone and RCI at 14 days post-injury. In contrast to the T-cell suppressive nature of myeloid-derived suppressor cells (MDSC) found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in IFN-γ and a decrease in IL-10. This is consistent with previous work in burn injury indicating that a MDSC-like population increases innate immunity. RCI results in the increase of distinct populations of Gr-1+ CD11b+cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host. PMID:23042190

  1. Delayed hepatobiliary injury in a decompression sickness patient after scuba diving: case report.

    PubMed

    Kim, Hee Duck; Lee, Sang Hwan; Eom, Huisu; Kang, Young Joong

    2016-01-01

    We report here the first case of liver injury in a 51-year-old man following a dive to a depth of 40 meters. He presented with typical neurological symptoms affecting the lower limbs. Five days later, he experienced delayed abdominal pain, followed by rapidly progressive liver and adjacent organ injury due to air emboli in the intrahepatic portal vein. He received supportive care and hyperbaric therapy with a U.S. Navy Treatment Table 6 and recovered. Decompression sickness is a disease of protean manifestations. More information about venous gas emboli may be useful for better assessing decompression sickness. In this case, radiologic evaluation of the abdomen and the presentation of air bubbles in the portal vein in computed tomography played an essential role in diagnosing induced venous gas emboli in the liver and adjacent organs.

  2. Delayed hepatobiliary injury in a decompression sickness patient after scuba diving: case report.

    PubMed

    Kim, Hee Duck; Lee, Sang Hwan; Eom, Huisu; Kang, Young Joong

    2016-01-01

    We report here the first case of liver injury in a 51-year-old man following a dive to a depth of 40 meters. He presented with typical neurological symptoms affecting the lower limbs. Five days later, he experienced delayed abdominal pain, followed by rapidly progressive liver and adjacent organ injury due to air emboli in the intrahepatic portal vein. He received supportive care and hyperbaric therapy with a U.S. Navy Treatment Table 6 and recovered. Decompression sickness is a disease of protean manifestations. More information about venous gas emboli may be useful for better assessing decompression sickness. In this case, radiologic evaluation of the abdomen and the presentation of air bubbles in the portal vein in computed tomography played an essential role in diagnosing induced venous gas emboli in the liver and adjacent organs. PMID:27416694

  3. Radiation-Related Injuries and Their Management: An Update

    PubMed Central

    Wunderle, Kevin; Gill, Amanjit S.

    2015-01-01

    Ionizing radiation (in the form of X-rays) is used for the majority of procedures in interventional radiology. This review article aimed at promoting safer use of this tool through a better understanding of radiation dose and radiation effects, and by providing guidance for setting up a quality assurance program. To this end, the authors describe different radiation descriptive quantities and their individual strengths and challenges, as well as the biologic effects of ionizing radiation, including patient-related effects such as tissue reactions (previously known as deterministic effects) and stochastic effects. In this article, the clinical presentation, immediate management, and clinical follow-up of these injuries are also discussed. Tissue reactions are important primarily from the patients' perspective, whereas stochastic effects are most relevant for pediatric patients and from an occupational viewpoint. The factors affecting the likelihood of skin reaction (the most common tissue reaction) are described, and how this condition should be managed is discussed. Setting up a robust quality assurance program around radiation dose is imperative for effective monitoring and reduction of radiation exposure to patients and operators. Recommendations for the pre-, peri-, and postprocedure periods are given, including recommendations for follow-up of high-dose cases. Special conditions such as pregnancy and radiation recall are also discussed. PMID:26038622

  4. Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

    SciTech Connect

    Oldfield, E.H.; Friedman, R.; Kinsella, T.; Moquin, R.; Olson, J.J.; Orr, K.; DeLuca, A.M. )

    1990-05-01

    To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms.

  5. Delayed and disorganised brain activation detected with magnetoencephalography after mild traumatic brain injury

    PubMed Central

    da Costa, Leodante; Robertson, Amanda; Bethune, Allison; MacDonald, Matt J; Shek, Pang N; Taylor, Margot J; Pang, Elizabeth W

    2015-01-01

    Background Awareness to neurocognitive issues after mild traumatic brain injury (mTBI) is increasing, but currently no imaging markers are available for mTBI. Advanced structural imaging recently showed microstructural tissue changes and axonal injury, mild but likely sufficient to lead to functional deficits. Magnetoencephalography (MEG) has high temporal and spatial resolution, combining structural and electrophysiological information, and can be used to examine brain activation patterns of regions involved with specific tasks. Methods 16 adults with mTBI and 16 matched controls were submitted to neuropsychological testing (Wechsler Abbreviated Scale of Intelligence (WASI); Conners; Alcohol Use Disorders Identification Test (AUDIT); Generalised Anxiety Disorder Seven-item Scale (GAD-7); Patient Health Questionnaire (PHQ-9); Symptom Checklist and Symptom Severity Score (SCAT2)) and MEG while tested for mental flexibility (Intra-Extra Dimensional set-shifting tasks). Three-dimensional maps were generated using synthetic aperture magnetometry beamforming analyses to identify differences in regional activation and activation times. Reaction times and accuracy between groups were compared using 2×2 mixed analysis of variance. Findings While accuracy was similar, patients with mTBI reaction time was delayed and sequence of activation of brain regions disorganised, with involvement of extra regions such as the occipital lobes, not used by controls. Examination of activation time showed significant delays in the right insula and left posterior parietal cortex in patients with mTBI. Conclusions Patients with mTBI showed significant delays in the activation of important areas involved in executive function. Also, more regions of the brain are involved in an apparent compensatory effort. Our study suggests that MEG can detect subtle neural changes associated with cognitive dysfunction and thus, may eventually be useful for capturing and tracking the onset and course of

  6. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.

    PubMed

    Detappe, Alexandre; Kunjachan, Sijumon; Sancey, Lucie; Motto-Ros, Vincent; Biancur, Douglas; Drane, Pascal; Guieze, Romain; Makrigiorgos, G Mike; Tillement, Olivier; Langer, Robert; Berbeco, Ross

    2016-09-28

    Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment. PMID:27423325

  7. Delayed regaining of gait ability in a patient with brain injury

    PubMed Central

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2016-01-01

    Abstract Background: Little is known about delay in regaining gait ability at a chronic stage after brain injury. In this study, we report on a single patient who regained the gait ability during 2 months of intensive rehabilitation starting 2 years after a brain injury. Methods and results: A 40-year-old male patient diagnosed with viral encephalitis underwent comprehensive rehabilitation until 2 years after onset. However, he could not even sit independently and presented with severe physical deconditioning and severe ataxia. To understand his neurological state, 4 neural tracts related to gait function were reconstructed, and based on the state of these neural tracts, we decided that the patient had the neurological potential to walk independently. Therefore, we assumed that the main reasons for gait inability in this patient were severe physical deconditioning and truncal ataxia. Consequently, the patient underwent the following intensive rehabilitative therapy: administration of drugs for control of ataxia (topiramate, clonazepam, and propranolol) and movement therapy for physical conditioning and gait training. As a result, after 2 months of rehabilitation, he was able to walk independently on an even floor, with improvement of severe physical deconditioning and truncal ataxia. Conclusion: We described the rehabilitation program in a single patient who regained the gait ability during 2 months of intensive rehabilitation starting 2 years after a brain injury. PMID:27661035

  8. Popliteal artery injuries in an urban trauma center with a rural catchment area: do delays in definitive treatment affect amputation?

    PubMed

    Simmons, Jon D; Gunter, Joseph W; Schmieg, Robert E; Manley, Justin D; Rushton, Fred W; Porter, John M; Mitchell, Marc E

    2011-11-01

    Extended length of time from injury to definitive vascular repair is considered to be a predictor of amputation in patients with popliteal artery injuries. In an urban trauma center with a rural catchment area, logistical issues frequently result in treatment delays, which may affect limb salvage after vascular trauma. We examined how known risk factors for amputation after popliteal trauma are affected in a more rural environment, where patients often experience delays in definitive surgical treatment. All adult patients admitted to the Level I trauma center, the University of Mississippi Medical Center, with a popliteal artery injury between January 2000 and December of 2007 were identified. Demographic information management and outcome data were collected. Body mass index, mangled extremity severity score (MESS), Guistilo open fracture score, injury severity score, and time from injury to vascular repair were examined. Fifty-one patients with popliteal artery injuries (53% blunt and 47% penetrating) were identified, all undergoing operative repair. There were nine amputations (17.6%) and one death. Patients requiring amputation had a higher MESS, 7.8 versus 5.3 (P < 0.01), and length of stay, 43 versus 15 days (P < 0.01), compared with those with successful limb salvage. Body mass index, injury severity score, Guistilo open fracture score, or time from injury to repair were not different between the two groups. Patients with a blunt mechanism of injury had a slightly higher amputation rate compared with those with penetrating trauma, 25.9 per cent versus 8.3 per cent (P = non significant). MESS, though not perfect, is the best predictor of amputation in patients with popliteal artery injuries. Morbid obesity is not a significant predictor for amputation in patients with popliteal artery injuries. Time from injury to repair of greater than 6 hours was not predictive of amputation. This study further demonstrates that a single scoring system should be used with

  9. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

    PubMed

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-12-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts.

  10. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation

    PubMed Central

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-01-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  11. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

    PubMed

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-12-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  12. Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015

    PubMed Central

    Satyamitra, Merriline M.; DiCarlo, Andrea L.; Taliaferro, Lanyn

    2016-01-01

    After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop. PMID:27387859

  13. Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015.

    PubMed

    Satyamitra, Merriline M; DiCarlo, Andrea L; Taliaferro, Lanyn

    2016-08-01

    After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop. PMID:27387859

  14. Sublethal radiation injury uncovers a functional transition during erythroid maturation

    PubMed Central

    Peslak, Scott A.; Wenger, Jesse; Bemis, Jeffrey C.; Kingsley, Paul D.; Frame, Jenna M.; Koniski, Anne D.; Chen, Yuhchyau; Williams, Jacqueline P.; McGrath, Kathleen E.; Dertinger, Stephen D.; Palis, James

    2012-01-01

    Objective Clastogenic injury of the erythroid lineage results in anemia, reticulocytopenia, and transient appearance of micronucleated reticulocytes (MN-RET). However, the MN-RET dose-response in murine models is only linear to 2 Gy total body irradiation (TBI) and paradoxically decreases at higher exposures, suggesting complex radiation effects on erythroid intermediates. To better understand this phenomenon, we investigated the kinetics and apoptotic response of the erythron to sublethal radiation injury. Materials and Methods We analyzed the response to 1 and 4 Gy TBI of erythroid progenitors and precursors using colony assays and imaging flow cytometry (IFC), respectively. We also investigated cell cycling and apoptotic gene expression of the steady-state erythron. Results Following 1 Gy TBI, erythroid progenitors and precursors were partially depleted. In contrast, essentially all bone marrow erythroid progenitors and precursors were lost within two days following 4 Gy irradiation. IFC analysis revealed preferential loss of phenotypic erythroid colony-forming units (CFU-E) and proerythroblasts immediately following sublethal irradiation. Furthermore, these populations underwent radiation-induced apoptosis, without changes in steady-state cellular proliferation, at much higher frequencies than later-stage erythroid precursors. Primary erythroid precursor maturation is associated with marked Bcl-xL upregulation and Bax and Bid down-regulation. Conclusions MN-RET loss following higher sublethal radiation exposures results from rapid depletion of erythroid progenitors and precursors. This injury reveals that CFU-E and proerythroblasts constitute a particularly proapoptotic compartment within the erythron. We conclude that the functional transition of primary proerythroblasts to later-stage erythroid precursors is characterized by a shift from a pro-apoptotic to an anti-apoptotic phenotype. PMID:21291953

  15. The Role of Proinflammatory Cytokine Interleukin-18 in Radiation Injury

    PubMed Central

    Xiao, Mang

    2016-01-01

    Abstract Massive radiation-induced inflammatory factors released from injured cells may cause innate and acquired immune reactions that can further result in stress response signal activity-induced local and systemic damage. IL‐1 family members IL‐1β, IL‐18, and IL‐33 play key roles in inflammatory and immune responses and have been recognized to have significant influences on the pathogenesis of diseases. IL‐1β, IL‐18, and IL‐33 share similarities of cytokine biology, but differences exist in signaling pathways. A key component of the inflammatory reaction is the inflammasome, which is a caspase‐1‐containing multiprotein oligomer. Pathological stimuli such as radiation can induce inflammasome and caspase‐1 activation, and subsequently cause maturation (activation) of pro-forms of IL‐1 and IL‐18 upon caspase‐1 cleavage. This caspase‐1 dependent and IL‐1 and IL‐18 associated cell damage is defined as pyroptosis. Activated IL‐1 and IL‐18 as proinflammatory cytokines drive pathology at different immune and inflammatory disorders through Toll-like receptor (TLR) signaling. While the mechanisms of IL‐1β-induced pathophysiology of diseases have been well studied, IL‐18 has received less attention. The author recently reported that gamma radiation highly increased IL‐1β, IL‐18 and IL‐33 expression in mouse thymus, spleen and/or bone marrow cells; also circulating IL‐18 can be used as a radiation biomarker to track radiation injury in mice, minipigs, and nonhuman primates. This mini-review focuses on the role of IL‐18 in response to gamma radiation-induced injury. PMID:27356067

  16. The Role of Proinflammatory Cytokine Interleukin-18 in Radiation Injury.

    PubMed

    Xiao, Mang

    2016-08-01

    Massive radiation-induced inflammatory factors released from injured cells may cause innate and acquired immune reactions that can further result in stress response signal activity-induced local and systemic damage. IL-1 family members IL-1β, IL-18, and IL-33 play key roles in inflammatory and immune responses and have been recognized to have significant influences on the pathogenesis of diseases. IL-1β, IL-18, and IL-33 share similarities of cytokine biology, but differences exist in signaling pathways. A key component of the inflammatory reaction is the inflammasome, which is a caspase-1-containing multiprotein oligomer. Pathological stimuli such as radiation can induce inflammasome and caspase-1 activation, and subsequently cause maturation (activation) of pro-forms of IL-1 and IL-18 upon caspase-1 cleavage. This caspase-1 dependent and IL-1 and IL-18 associated cell damage is defined as pyroptosis. Activated IL-1 and IL-18 as proinflammatory cytokines drive pathology at different immune and inflammatory disorders through Toll-like receptor (TLR) signaling. While the mechanisms of IL-1β-induced pathophysiology of diseases have been well studied, IL-18 has received less attention. The author recently reported that gamma radiation highly increased IL-1β, IL-18 and IL-33 expression in mouse thymus, spleen and/or bone marrow cells; also circulating IL-18 can be used as a radiation biomarker to track radiation injury in mice, minipigs, and nonhuman primates. This mini-review focuses on the role of IL-18 in response to gamma radiation-induced injury.

  17. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    SciTech Connect

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-04-01

    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 {beta} 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.

  18. Radiation injury of the rectum: evaluation of surgical treatment

    SciTech Connect

    Anseline, P.F.; Lavery, I.C.; Fazio, V.W.; Jagelman, D.G.; Weakley, F.L.

    1981-12-01

    One hundred four patients, 80 women and 24 men, with radiation injury of the rectum following treatment for gynecologic and urologic malignancy were studied. In 50 patients, the rectal injury was treated surgically; 54 patients were treated conservatively. The age and sex distributions were the same in each group. In 63 patients, symptoms developed one month to one year after radiotherapy. The longest latent interval was 17 years. Of the 50 surgical patients, 23 had associated small bowel injury. The indications for surgery for the rectal injury were 1) proctitis unresponsive to conservative measures in 14 patients, 2) rectal stricture or fistula or both in 32, and 3) rectosigmoid perforation in four. Forty-one patients had external diversions. Eleven had intestinal continuity restored; six of the 11 had required the stoma for proctitis unresponsive to medical measures. Nineteen patients did not undergo colostomy closure, although symptoms wer greatly improved. Diversion alone was insufficient treatment in the remaining 11 patients. Twenty-six patients died. The 12 deaths in the surgical group comprised four due to residual malignancy, four from postoperative complications, and four from unrelated causes. Of the 14 deaths in the nonsurgical group, 11 died of the primary malignancy and three of unrelated causes. Diversion is considered the safest form of treatment for rectovaginal fistulae, rectal strictures, and proctitis unresponsive to medical measures. Intestinal resection resulted in sharp rise in the morbidity and mortality rates.

  19. Radiation injury of the rectum: Evaluation of surgical treatment

    SciTech Connect

    Anseline, P.F.; Lavery, I.C.; Fazio, V.W.; Jagelman, D.G.; Weakley, F.L.

    1981-12-01

    One hundred four patients, 80 women and 24 men, with radiation injury of the rectum following treatment for gynecologic and urologic malignancy were studied. In 50 patients, the rectal injury was treated surgically; 54 patients were treated conservatively. The age and sex distributions were the same in each group. In 63 patients, symptoms developed one month to one year after radiotherapy. The longest latent interval was 17 years. Of the 50 surgical patients, 23 had associated small bowel injury. The indications for surgery for the rectal injury were 1) proctitis unresponsive to conservative measures in 14 patients, 2) rectal stricture or fistula or both in 32, and 3) rectosigmoid perforation in four. Forty-one patients had external diversions. Eleven had intestinal continuity restored; six of the 11 had required the stoma for proctitis unresponsive to medical measures. Nineteen patients did not undergo colostomy closure, although symptoms were greatly improved. Diversion alone was insufficient treatment in the remaining 11 patients. Twenty-six patients died. The 12 deaths in the surgical group comprised four due to residual malignancy, four from post-operative complications, and four from unrelated causes. Of the 14 deaths in the nonsurgical group, 11 died of the primary malignancy and three of unrelated causes. Diversion is considered the safest form of treatment for rectovaginal fistulae, rectal strictures, and proctitis unresponsive to medical measures. Intestinal resection resulted in a sharp rise in the morbidity and mortality rates.

  20. Radiation-induced cell cycle delay measured in two mouse tumors in vivo using bromodeoxyuridine

    SciTech Connect

    Wilson, G.D.; Martindale, C.A.; Soranson, J.A.; Bourhis, J.; Carl, U.M.; McNally, N.J. )

    1994-02-01

    The magnitude of the delay of cells in the phases of the cell cycle after irradiation may be related to the radioresponsiveness of tumor cell populations. In this study we have quantified division delay in two mouse tumors in vivo after single and fractionated doses of X rays and single doses of neutrons. The incorporation of bromodeoxyuridine and flow cytometry provided a sensitive and quantitative method to detect cell cycle perturbations after radiation treatment. The more rapidly growing SAF tumor showed less G[sub 2]-phase delay per gray than a more slowly proliferating tumor, the Rh (0.9 vs 1.8 h). In addition, the SAF tumor failed to show any G[sub 1]/S-phase delay while the Rh tumor experienced a longer G[sub 1]-phase delay while the Rh tumor experienced a longer G[sub 1]-phase delay than that measured for G[sub 2] phase (3.1 vs 1.8 h). There was a trend in both tumors for lower doses to be more effective in producing cell cycle delays. Neutrons caused longer G[sub 2]-phase delays on a unit dose basis, 2.5 and 5.4 h for the SAF and Rh tumors, respectively. The RBE for neutrons for division delay was found to be 2.9 and 2.8 for the SAF and Rh tumors, while the RBE for growth delay was 3.4 and 3.5. Fractionation of the X-ray dose caused a reduction in division delay at higher total doses (10 or 12 Gy) but was without effect at the lower dose studied (6 Gy). These studies show the feasibility of measuring cell cycle delays in vivo, and future developments are suggested for a possible predictive test in patients receiving radiotherapy. 17 refs., 6 figs., 2 tabs.

  1. Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

    PubMed Central

    Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

    2012-01-01

    Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

  2. Extracellular Vesicles and Vascular Injury: New Insights for Radiation Exposure.

    PubMed

    Flamant, Stéphane; Tamarat, Radia

    2016-08-01

    This article reviews our current knowledge about cell-derived extracellular vesicles (EVs), including microparticles and exosomes, and their emergence as mediators of a new important mechanism of cell-to-cell communication. Particular emphasis has been given to the increasing involvement of EVs in the field of radiation-induced vascular injury. Although EVs have been considered for a long time as cell "dust", they in fact precisely reflect the physiological state of the cells. The role of microparticles and exosomes in mediating vascular dysfunction suggests that they may represent novel pathways in short- or long-distance paracrine intercellular signaling in vascular environment. In this article, the mechanisms involved in the biogenesis of microparticles and exosomes, their composition and participation in the pathogenesis of vascular dysfunction are discussed. Furthermore, this article highlights the concept of EVs as potent vectors of biological information and protagonists of an intercellular communication network. Special emphasis is made on EV-mediated microRNA transfer and on the principal consequences of such signal exchange on vascular injury and radiation-induced nontargeted effect. The recent progress in elucidating the biology of EVs has provided new insights for the field of radiation, advancing their use as diagnostic biomarkers or in therapeutic interventions. PMID:27459703

  3. Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation.

    PubMed

    Malyszko, Jolanta; Lukaszyk, Ewelina; Glowinska, Irena; Durlik, Magdalena

    2015-01-01

    Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness. PMID:26175216

  4. Space radiation-associated lung injury in a murine model.

    PubMed

    Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Schweitzer, Kelly S; Berdyshev, Evgeny V; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S; Yu, Yongjia; Globus, Ruth K; Solomides, Charalambos C; Ullrich, Robert L; Petrache, Irina

    2015-03-01

    Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions. PMID:25526737

  5. Space radiation-associated lung injury in a murine model

    PubMed Central

    Pietrofesa, Ralph A.; Arguiri, Evguenia; Schweitzer, Kelly S.; Berdyshev, Evgeny V.; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S.; Yu, Yongjia; Globus, Ruth K.; Solomides, Charalambos C.; Ullrich, Robert L.; Petrache, Irina

    2014-01-01

    Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to 137Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u 56Fe ions, or 350 MeV/u 28Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy 56Fe or 28Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions. PMID:25526737

  6. Space radiation-associated lung injury in a murine model.

    PubMed

    Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Schweitzer, Kelly S; Berdyshev, Evgeny V; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S; Yu, Yongjia; Globus, Ruth K; Solomides, Charalambos C; Ullrich, Robert L; Petrache, Irina

    2015-03-01

    Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions.

  7. Delayed neurological deterioration after surgery for intraspinal meningiomas: Ischemia-reperfusion injury in a rat model

    PubMed Central

    WU, LIANG; YANG, TAO; YANG, CHENLONG; YAO, NING; WANG, HUILIANG; FANG, JINGYI; XU, YULUN

    2015-01-01

    Delayed neurological deterioration in the absence of direct cord insult following surgical removal and cord decompression is a rare but severe postoperative complication in a small subset of patients with intraspinal meningiomas. To date, the underlying pathophysiology of such a finding remains unclear and ischemia-reperfusion injury (IRI) is considered as the potential etiology in the literature. However, no experimental research has been reported to prove this hypothesis. The present study investigated whether IRI occurs following decompression surgery using an experimental rat model of chronic compressive spinal cord injury (SCI). A chronic spinal cord compression model was developed with various sizes of polymer sheets (mild and severe compression) that were microsurgically implanted underneath the T8-9 laminae, and occurrence of IRI in the spinal cord following decompression was determined by measuring superoxide dismutase (SOD) level and malondialdehyde (MDA) concentration. In the mild compression groups, after decompression SOD activities significantly increased along with a reduction in MDA content compared with the non-decompression group (P<0.05), which exhibited diminishment of lipid peroxidation and relief of the secondary injury. These findings indicated that decompression is effective to improve neurological recovery and may deliver improved outcomes for chronic mild compression of the spinal cord. However, in severe compression groups, after decompression, SOD activities markedly reduced further along with a significant increase in MDA content compared with non-decompression group (P<0.05). The results indicated that lipid peroxidation increased immediately after decompression surgery which resulted from reperfusion of the spinal cord. These findings demonstrated IRI may occur as a result of chronic severe compression of the spinal cord. In clinical practice, sudden cord expansion and reperfusion may have lead to disruption in the blood spinal cord

  8. Management of ionizing radiation injuries and illnesses, Part 3: Radiobiology and health effects of ionizing radiation.

    PubMed

    Christensen, Doran M; Livingston, Gordon K; Sugarman, Stephen L; Parillo, Steven J; Glassman, Erik S

    2014-07-01

    Ionizing radiation exposure can induce profound changes in intracellular components, potentially leading to diverse health effects in exposed individuals. Any cellular component can be damaged by radiation, but some components affect cellular viability more profoundly than others. The ionization caused by radiation lasts longer than the initial inciting incident, continuing as 1 ionization incident causes another. In some cases, damage to DNA can lead to cellular death at mitosis. In other cases, activation of the genetic machinery can lead to a genetic cascade potentially leading to mutations or cell death by apoptosis. In the third of 5 articles on the management of injuries and illnesses caused by ionizing radiation, the authors provide a clinically relevant overview of the pathophysiologic process associated with potential exposure to ionizing radiation.

  9. Influence of the circadian rhythm in cell division on radiation-induced mitotic delay in vivo

    SciTech Connect

    Rubin, N.H.

    1982-01-01

    Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study demonstrated a dose-response effect on length of mitotic delay and, to a lesser extent, degree of recovery.

  10. Radiation injury is a potentially serious complication to fluoroscopically-guided complex interventions

    PubMed Central

    Wagner, LK

    2007-01-01

    Radiation-induced injury to skin is an infrequent but potentially serious complication to complex fluoroscopically-guided interventional procedures. Due to a lack of experience with such injuries, the medical community has found fluoroscopically-induced injuries difficult to diagnose. Injuries have occurred globally in many countries. Serious injuries most frequently occur on the back but have also occurred on the neck, buttocks and anterior of the chest. Severities of injuries range from skin rashes and epilation to necrosis of the skin and its underlying structures. This article reviews the characteristics of these injuries and some actions that can be taken to reduce their likelihood or seriousness. PMID:21614271

  11. The Evolving Mcart Multimodal Imaging Core: Establishing a Protocol for Computed Tomography and Echocardiography in the Rhesus Macaque to Perform Longitudinal Analysis of Radiation-Induced Organ Injury.

    PubMed

    de Faria, Eduardo B; Barrow, Kory R; Ruehle, Bradley T; Parker, Jordan T; Swartz, Elisa; Taylor-Howell, Cheryl; Kieta, Kaitlyn M; Lees, Cynthia J; Sleeper, Meg M; Dobbin, Travis; Baron, Adam D; Mohindra, Pranshu; MacVittie, Thomas J

    2015-11-01

    Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities that produce critical longitudinal data that can be analyzed for radiation-induced organ-specific injury to the lung and heart. The Medical Countermeasures Against Radiological Threats (MCART) consortium has a well established animal model research platform that includes nonhuman primate (NHP) models of the acute radiation syndrome and the delayed effects of acute radiation exposure. These models call for a definition of the latency, incidence, severity, duration, and resolution of different organ-specific radiation-induced subsyndromes. The pulmonary subsyndromes and cardiac effects are a pair of interdependent syndromes impacted by exposure to potentially lethal doses of radiation. Establishing a connection between these will reveal important information about their interaction and progression of injury and recovery. Herein, the authors demonstrate the use of CT and EC data in the rhesus macaque models to define delayed organ injury, thereby establishing: a) consistent and reliable methodology to assess radiation-induced damage to the lung and heart; b) an extensive database in normal age-matched NHP for key primary and secondary endpoints; c) identified problematic variables in imaging techniques and proposed solutions to maintain data integrity; and d) initiated longitudinal analysis of potentially lethal radiation-induced damage to the lung and heart.

  12. Delayed protective effect of telmisartan on lung ischemia/reperfusion injury in valve replacement operations

    PubMed Central

    Fan, Yongfeng; Zhang, Daguo; Xiang, Daokang

    2016-01-01

    The present study aimed to investigate the delayed protective effect of telmisartan on lung ischemic/reperfusion injury in patients undergoing heart valve replacement operations. In total, 180 patients diagnosed with rheumatic valve diseases were randomly divided into the telmisartan (T), captopril (C) and placebo (P) groups. In the telmisartan group, the patients were pretreated with telmisartan (1 mg/kg/day), at the time period 96–48 h before the operation, whereas in the C group, the patients were treated with captopril (1 mg/kg/day) at the time period 96–48 h prior to the operation control group. Each drug treatment group included a corresponding placebo treatment. The variables pulmonary vascular resistance (PVR) and A-aDO2 were measured prior to CPB and at 1, 3, 6 and 12 h after CPB. Pulmonary neutrophil (PMN) count in the left and right atrium blood as well as SOD malondialdehyde (MDA), NO, angiotensin II (AngII) value in the left atrium blood, were measured 30 min prior to and after CPB. The PVR parameters of the telmisartan and captopril groups were significantly lower than those of the placebo group (P<0.05). The A-aDO2 values in the telmisartan and captopril groups were significantly lower than those in the placebo group at 1, 3 and 6 h following CPB treatment. The difference between the right and left atrium blood PMN was significantly lower in the telmisartan and captopril intervention groups compared to that in the placebo group 30 min following CPB treatment. The left atrium blood SOD and NO values were significantly higher, whereas the MDA value was significantly lower in the telmisartan group compared to the control group 30 min following CPB treatment. As for AngII, there was no difference between the C and T groups, compared with the P group. In the two groups 30 min after treatment with CPB, 24 patients experienced varying degrees of cough, with the telmisartan group showing a significant difference (P<0.05). The hospitalization time was

  13. Fever Is Associated with Delayed Ventilator Liberation in Acute Lung Injury

    PubMed Central

    Dowdy, David W.; Harrington, Thelma; Chandolu, Satish; Dinglas, Victor D.; Shah, Nirav G.; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Shanholtz, Carl; Hasday, Jeffrey D.; Needham, Dale M.

    2013-01-01

    Background: Acute lung injury (ALI) is characterized by inflammation, leukocyte activation, neutrophil recruitment, endothelial dysfunction, and epithelial injury, which are all affected by fever. Fever is common in the intensive care unit, but the relationship between fever and outcomes in ALI has not yet been studied. We evaluated the association of temperature dysregulation with time to ventilator liberation, ventilator-free days, and in-hospital mortality. Methods: Analysis of a prospective cohort study, which recruited consecutive patients with ALI from 13 intensive care units at four hospitals in Baltimore, Maryland. The relationship of fever and hypothermia with ventilator liberation was assessed with a Cox proportional hazards model. We evaluated the association of temperature during the first 3 days after ALI with ventilator-free days, using multivariable linear regression models, and the association with mortality was evaluated by robust Poisson regression. Measurements and Main Results: Of 450 patients, only 12% were normothermic during the first 3 days after ALI onset. During the first week post-ALI, each additional day of fever resulted in a 33% reduction in the likelihood of successful ventilator liberation (95% confidence interval [CI] for adjusted hazard ratio, 0.57 to 0.78; P < 0.001). Hypothermia was independently associated with decreased ventilator-free days (hypothermia during each of the first 3 d: reduction of 5.58 d, 95% CI: –9.04 to –2.13; P = 0.002) and increased mortality (hypothermia during each of the first 3 d: relative risk, 1.68; 95% CI, 1.06 to 2.66; P = 0.03). Conclusions: Fever and hypothermia are associated with worse clinical outcomes in ALI, with fever being independently associated with delayed ventilator liberation. PMID:24024608

  14. Protective effects of ulinastatin and methylprednisolone against radiation-induced lung injury in mice

    PubMed Central

    Sun, Yu; Du, Yu-Jun; Zhao, Hui; Zhang, Guo-Xing; Sun, Ni; Li, Xiu-Jiang

    2016-01-01

    The effectiveness of ulinastatin and methylprednisolone in treating pathological changes in mice with radiation-induced lung injury (RILI) was evaluated. Forty C57BL/6 female mice received whole-chest radiation (1.5 Gy/min for 12 min) and were randomly allocated into Group R (single radiation, n = 10), Group U (ulinastatin treatment, n = 10), Group M (methylprednisolone treatment, n = 10), or Group UM (ulinastatin and methylprednisolone treatment, n = 10). Another 10 untreated mice served as controls (Group C). Pathological changes in lung tissue, pulmonary interstitial area density (PIAD) and expression levels of transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in lung tissue, serum and bronchoalveolar lavage fluid were determined. Alleviation of pathological changes in lung tissue was observed in Groups U, M and UM. Treatment with ulinastatin, methylprednisolone or both effectively delayed the development of fibrosis at 12 weeks after radiation. Ulinastatin, methylprednisolone or both could alleviate the radiation-induced increase in the PIAD (P < 0.05 or P < 0.01). Treatment with ulinastatin, methylprednisolone or both significantly reduced the expression of TNF-α, but not TGF-β1, at 9 weeks after radiation compared with Group R (P < 0.01). Ulinastatin and/or methylprednisolone effectively decreased the level of TNF-α in lung tissue after RILI and inhibited both the inflammatory response and the development of fibrosis. PMID:27342837

  15. Effects of Podophyllum hexandrum on radiation induced delay of postnatal appearance of reflexes and physiological markers in rats irradiated in utero.

    PubMed

    Goel, H C; Sajikumar, S; Sharma, Ashok

    2002-07-01

    Effect of 2.0 Gy gamma-dose delivered to rats in utero on 17th day of gestation was studied to monitor the radiation induced retardation of neurophysiological development in postnatal young ones. Rhizome of Podophyllum hexandrum which has been well documented for mitigating radiation injuries in adult mice was attempted for modifying radiation damage. Rats were observed from postnatal day 1 to 25 for the age of the appearance of physiological markers (pinna detachment, inscisor's eruption, eye opening) and acquisition of reflexes (surface righting, visual placing, reflex suspension, negative geotaxis). In irradiated groups there was a significant weight reduction in mother rats and offsprings throughout the experimental period. There was radiation-induced delay in the appearance of pinna detachment but not in eye opening and inscisor's eruption. Appearance of the reflexes were also delayed due to irradiation. Preirradiation administration of the extract of Podophyllum hexandrum (i.p., 200 mg/kg/b.w.) mitigated radiation induced postnatal physiological alterations. These studies have implications in protection against damage (in utero) due to planned radiation exposure.

  16. [A Case of Delayed Vascular Injury as a Complication Related to Implanted Central Venous Port Catheter].

    PubMed

    Sumiyoshi, Tetsuya; Kondo, Tomohiro; Fujii, Ryoji; Minagawa, Takeyoshi; Fujie, Shinya; Kimura, Tomohiro; Ihara, Hideyuki; Yoshizaki, Naohito; Kondo, Hitoshi; Kitayama, Hiromitsu; Sugiyama, Junko; Hirayama, Michiaki; Tsuji, Yasushi; Yamamoto, Kazuyuki; Kawarada, You; Okushiba, Shunichi; Nishioka, Noriko; Shimizu, Tadashi

    2015-12-01

    A 74-year-old woman with advanced gastric cancer was admitted to our hospital. A central venous (CV) port catheter was implanted into the right subclavian vein for preoperative chemotherapy and parenteral nutritional management. On the 35th day after implantation, she complained of diarrhea, fever and dyspnea. The chest radiograph showed a right-sided massive pleural effusion. As the patient progressively fell into severe respiratory distress, endotracheal intubation was performed for management of respiration by mechanical ventilation. Initially, given the patient's symptoms, she was diagnosed with septic shock. Therefore, after placement of a CV catheter through the right femoral vein, in consideration of the possibility of a port infection, she was treated with thoracentesis and infusion of antibiotics. The patient gradually recovered, and again received parenteral nutrition through the CV port catheter. After the infusion was administered, she complained of dyspnea. A CT scan of the chest revealed a right pleural effusion and displacement of the tip of the CV port catheter out of the wall of the superior vena cava. We diagnosed delayed vascular injury (DVI), and the CV port catheter was removed. She soon recovered with conservative treatment. We speculated that the initial respiratory symptoms such as the pleural effusion were caused by DVI. DVI should therefore be recognized as a complication related to implanted CV port catheters. PMID:26809313

  17. Blast injury in a civilian trauma setting is associated with a delay in diagnosis of traumatic brain injury.

    PubMed

    Bochicchio, Grant V; Lumpkins, Kimberly; O'Connor, James; Simard, Marc; Schaub, Stacey; Conway, Anne; Bochicchio, Kelly; Scalea, Thomas M

    2008-03-01

    High-pressure waves (blast) account for the majority of combat injuries and are becoming increasingly common in terrorist attacks. To our knowledge, there are no data evaluating the epidemiology of blast injury in a domestic nonterrorist setting. Data were analyzed retrospectively on patients admitted with any type of blast injury over a 10-year period at a busy urban trauma center. Injuries were classified by etiology of explosion and anatomical location. Eighty-nine cases of blast injury were identified in 57,392 patients (0.2%) treated over the study period. The majority of patients were male (78%) with a mean age of 40 +/- 17 years. The mean Injury Severity Score was 13 +/- 11 with an admission Trauma and Injury Severity Score of 0.9 +/- 0.2 and Revised Trauma Score of 7.5 +/- 0.8. The mean intensive care unit and hospital length of stay was 2 +/- 7 days and 4.6 +/- 10 days, respectively, with an overall mortality rate of 4.5 per cent. Private dwelling explosion [n = 31 (35%)] was the most common etiology followed by industrial pressure blast [n = 20 (22%)], industrial gas explosion [n = 16 (18%)], military training-related explosion [n = 15 (17%)], home explosive device [n = 8 (9%)], and fireworks explosion [n = 1 (1%)]. Maxillofacial injuries were the most common injury (n = 78) followed by upper extremity orthopedic (n = 29), head injury (n = 32), abdominal (n = 30), lower extremity orthopedic (n = 29), and thoracic (n = 19). The majority of patients with head injury [28 of 32 (88%)] presented with a Glasgow Coma Scale score of 15. CT scans on admission were initially positive for brain injury in 14 of 28 patients (50%). Seven patients (25%) who did not have a CT scan on admission had a CT performed later in their hospital course as a result of mental status change and were positive for traumatic brain injury (TBI). Three patients (11%) had a negative admission CT with a subsequently positive CT for TBI over the next 48 hours. The remaining four patients (14

  18. Reversal of Established Traumatic Brain Injury-Induced, Anxiety-Like Behavior in Rats after Delayed, Post-Injury Neuroimmune Suppression

    PubMed Central

    Rodgers, Krista M.; Deming, Yuetiva K.; Bercum, Florencia M.; Chumachenko, Serhiy Y.; Wieseler, Julie L.; Johnson, Kirk W.; Watkins, Linda R.

    2014-01-01

    Abstract Traumatic brain injury (TBI) increases the risk of neuropsychiatric disorders, particularly anxiety disorders. Yet, there are presently no therapeutic interventions to prevent the development of post-traumatic anxiety or effective treatments once it has developed. This is because, in large part, of a lack of understanding of the underlying pathophysiology. Recent research suggests that chronic neuroinflammatory responses to injury may play a role in the development of post-traumatic anxiety in rodent models. Acute peri-injury administration of immunosuppressive compounds, such as Ibudilast (MN166), have been shown to prevent reactive gliosis associated with immune responses to injury and also prevent lateral fluid percussion injury (LFPI)-induced anxiety-like behavior in rats. There is evidence in both human and rodent studies that post-traumatic anxiety, once developed, is a chronic, persistent, and drug-refractory condition. In the present study, we sought to determine whether neuroinflammation is associated with the long-term maintenance of post-traumatic anxiety. We examined the efficacy of an anti-inflammatory treatment in decreasing anxiety-like behavior and reactive gliosis when introduced at 1 month after injury. Delayed treatment substantially reduced established LFPI-induced freezing behavior and reactive gliosis in brain regions associated with anxiety and continued neuroprotective effects were evidenced 6 months post-treatment. These results support the conclusion that neuroinflammation may be involved in the development and maintenance of anxiety-like behaviors after TBI. PMID:24041015

  19. Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

    PubMed Central

    Shao, Lijian; Luo, Yi

    2014-01-01

    Abstract Significance: Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Recent Advances: Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Critical Issues: Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. Future Directions: In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression. Antioxid. Redox Signal. 20, 1447–1462. PMID:24124731

  20. Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury

    PubMed Central

    Zachman, Derek K.; Leon, Ronald P.; Das, Prerna; Goldman, Devorah C.; Hamlin, Kimberly L.; Guha, Chandan; Fleming, William H.

    2014-01-01

    Endothelial cells (ECs) are an essential component of the hematopoietic microenvironment, which maintains and regulates hematopoietic stem cells (HSCs). Although ECs can support the regeneration of otherwise lethally-irradiated HSCs, the mechanisms are not well understood. To further understand this phenomenon, we studied HSC regeneration from irradiated bone marrow using co-culture with human aortic endothelial cells (HAECs). Co-culture with HAECs induced a 24-fold expansion of long-term HSCs (CD150+, lineagelo, Sca-1+, c-Kit+; CD150+LSK cells) in vitro. These cells gave rise to functional hematopoietic stem and progenitor cells (HSPCs) with colony-forming activity, multilineage reconstitution and serial transplantation potential. Furthermore, HAECs significantly reduced DNA damage in irradiated LSK cells within 24 hours. Remarkably, we were able to delay the exposure of irradiated bone marrow to the regenerative, HAEC-derived signals for up to 48 hours and still rescue functional HSCs. G-CSF is the gold standard for promoting hematopoietic regeneration in vivo. However, when compared to HAECs, in vitro G-CSF treatment promoted lineage differentiation and regenerated 5-fold fewer CD150+LSK cells. Together, our results show that HAECs are powerful, direct mitigators of HSC injury and DNA damage. Identification of the HAEC-derived factors that rescue HSCs may lead to improved therapies for hematopoietic regeneration after radiation injury. PMID:23939266

  1. Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury.

    PubMed

    Zachman, Derek K; Leon, Ronald P; Das, Prerna; Goldman, Devorah C; Hamlin, Kimberly L; Guha, Chandan; Fleming, William H

    2013-11-01

    Endothelial cells (ECs) are an essential component of the hematopoietic microenvironment, which maintains and regulates hematopoietic stem cells (HSCs). Although ECs can support the regeneration of otherwise lethally-irradiated HSCs, the mechanisms are not well understood. To further understand this phenomenon, we studied HSC regeneration from irradiated bone marrow using co-culture with human aortic ECs (HAECs). Co-culture with HAECs induced a 24-fold expansion of long-term HSCs (CD150(+), lineage(lo), Sca-1(+), c-Kit(+); CD150(+)LSK cells) in vitro. These cells gave rise to functional hematopoietic stem and progenitor cells (HSPCs) with colony-forming activity, multilineage reconstitution and serial transplantation potential. Furthermore, HAECs significantly reduced DNA damage in irradiated LSK cells within 24h. Remarkably, we were able to delay the exposure of irradiated bone marrow to the regenerative, HAEC-derived signals for up to 48h and still rescue functional HSCs. G-CSF is the gold standard for promoting hematopoietic regeneration in vivo. However, when compared to HAECs, in vitro G-CSF treatment promoted lineage differentiation and regenerated 5-fold fewer CD150(+)LSK cells. Together, our results show that HAECs are powerful, direct mitigators of HSC injury and DNA damage. Identification of the HAEC-derived factors that rescue HSCs may lead to improved therapies for hematopoietic regeneration after radiation injury. PMID:23939266

  2. Combined radiation and burn injury results in exaggerated early pulmonary inflammation

    PubMed Central

    Palmer, Jessica L.; Deburghgraeve, Cory R.; Bird, Melanie D.; Hauer-Jensen, Martin; Chen, Michael M.; Yong, Sherri; Kovacs, Elizabeth J.

    2014-01-01

    Events such as a nuclear meltdown accident or nuclear attack have potential for severe radiation injuries. Radiation injury frequently occurs in combination with other forms of trauma, most often burns. Thus far, combined injury studies have focused mainly on skin wound healing and damage to the gut. Since both radiation exposure and remote burn have pulmonary consequences, we examined the early effects of combined injury on the lung. C57BL/6 male mice were subjected to 5 Gy of total body irradiation followed by a 15% total body surface area scald burn. Lungs from surviving animals were examined for evidence of inflammation and pneumonitis. At 48 hours post-injury, pathology of the lungs from combined injury mice showed greater inflammation compared to all other treatment groups, with marked red blood cell and leukocyte congestion of the pulmonary vasculature. There was excessive leukocyte accumulation, primarily neutrophils, in the vasculature and interstitium, with occasional cells in the alveolar space. At 24 and 48 hours post-injury, myeloperoxidase levels in lungs of mice given combined injury were elevated compared to all other treatment groups (p<0.01), confirming histological evidence of neutrophil accumulation. Pulmonary levels of the neutrophil chemoattractant KC (CXCL1) were 3 times above that of either injury alone (p<0.05). Further, monocyte chemotactic protein-1 (MCP-1, CCL2) was increased 2-fold and 3-fold compared to burn injury or radiation injury, respectively (p<0.05). Together, these data suggest that combined radiation and burn injury augments early pulmonary congestion and inflammation.. Currently, countermeasures for this unique type of injury are extremely limited. Further research is needed to elucidate the mechanisms behind the synergistic effects of combined injury in order to develop appropriate treatments. PMID:23899376

  3. Laminin 332 Deposition is Diminished in Irradiated Skin in an Animal Model of Combined Radiation and Wound Skin Injury

    PubMed Central

    Jourdan, M. M.; Lopez, A.; Olasz, E. B.; Duncan, N. E.; Demara, M.; Kittipongdaja, W.; Fish, B. L.; Mäder, M.; Schock, A.; Morrow, N. V.; Semenenko, V. A.; Baker, J. E.; Moulder, J. E.; Lazarova, Z.

    2011-01-01

    Skin exposure to ionizing radiation affects the normal wound healing process and greatly impacts the prognosis of affected individuals. We investigated the effect of ionizing radiation on wound healing in a rat model of combined radiation and wound skin injury. Using a soft X-ray beam, a single dose of ionizing radiation (10–40 Gy) was delivered to the skin without significant exposure to internal organs. At 1 h postirradiation, two skin wounds were made on the back of each rat. Control and experimental animals were euthanized at 3, 7, 14, 21 and 30 days postirradiation. The wound areas were measured, and tissue samples were evaluated for laminin 332 and matrix metalloproteinase (MMP) 2 expression. Our results clearly demonstrate that radiation exposure significantly delayed wound healing in a dose-related manner. Evaluation of irradiated and wounded skin showed decreased deposition of laminin 332 protein in the epidermal basement membrane together with an elevated expression of all three laminin 332 genes within 3 days postirradiation. The elevated laminin 332 gene expression was paralleled by an elevated gene and protein expression of MMP2, suggesting that the reduced amount of laminin 332 in irradiated skin is due to an imbalance between laminin 332 secretion and its accelerated processing by elevated tissue metalloproteinases. Western blot analysis of cultured rat keratinocytes showed decreased laminin 332 deposition by irradiated cells, and incubation of irradiated keratinocytes with MMP inhibitor significantly increased the amount of deposited laminin 332. Furthermore, irradiated keratinocytes exhibited a longer time to close an artificial wound, and this delay was partially corrected by seeding keratinocytes on laminin 332-coated plates. These data strongly suggest that laminin 332 deposition is inhibited by ionizing radiation and, in combination with slower keratinocyte migration, can contribute to the delayed wound healing of irradiated skin. PMID

  4. Vascular response to radiation injury in the rat lung.

    PubMed

    Peterson, L M; Evans, M L; Graham, M M; Eary, J F; Dahlen, D D

    1992-02-01

    Changes in relative left-to-right lung blood flow ratios were followed as an index of vascular radiation injury in left-hemithorax-irradiated Sprague-Dawley rats. Single doses of 11 to 21 Gy gamma radiation resulted in a dose-dependent decrease in relative blood flow to the irradiated lung from 3 to 5 weeks after exposure during the development of pneumonitis. Blood flow returned to near normal by 5 weeks after lower doses (11-13.5 Gy). After a single dose of 15 Gy the left-to-right blood flow ratio recovered to 75% of normal at 12 weeks and leveled off. Following 18 Gy irradiation a second period of reduced flow began 16 weeks after exposure. After 21 Gy irradiation flow to the irradiated side remained low for 1 year after exposure. Rats that received a single dose of 18 Gy to the left hemithorax were also treated with one or two of the following drugs: captopril, cyproheptadine, dexamethasone, diethylcarbamazine, penicillamine, or theophylline. Dexamethasone was most effective at preventing the decrease in blood flow to the irradiated lung when treatment was continued through the pneumonitis period and dose was not tapered until 8 weeks after radiation exposure. All other drugs and drug combinations were, for the most part, virtually ineffective after the pneumonitis period. There was a relatively poor correlation with earlier vascular permeability surface area product studies. This suggests that endothelial damage, as well as damage to other cell types, contributes to the development of post-irradiation fibrosis in the lung. PMID:1734443

  5. Radiation combined injury models to study the effects of interventions and wound biomechanics.

    PubMed

    Zawaski, Janice A; Yates, Charles R; Miller, Duane D; Kaffes, Caterina C; Sabek, Omaima M; Afshar, Solmaz F; Young, Daniel A; Yang, Yunzhi; Gaber, M Waleed

    2014-12-01

    In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and burn and/or wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize wound closure. The first was an open wound model in mice to study the effect of wound size in combination with whole-body 6 Gy irradiation on the rate of wound closure, animal weight and survival (morbidity). In this model the addition of interventions, wound closure, subcutaneous vehicle injection, topical antiseptic and topical antibiotics were studied to measure their effect on healing and survival. The second was a rat closed wound model to study the biomechanical properties of a healed wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and wound pathology by staining with hematoxylin and eosin, trichrome, CD68 and Ki67. In the mouse open wound model, we found that wound size and morbidity were positively correlated, while wound size and survival were negatively correlated. Regardless of the wound size, the addition of radiation exposure delayed the healing of the wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ∼9 days. In the rat closed wound model we found that radiation exposure significantly decreased all wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of collagen/epithelial hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing wound size in combination with radiation

  6. UV radiation induces delayed hyperrecombination associated with hypermutation in human cells.

    PubMed

    Durant, Stephen T; Paffett, Kimberly S; Shrivastav, Meena; Timmins, Graham S; Morgan, William F; Nickoloff, Jac A

    2006-08-01

    Ionizing radiation induces delayed genomic instability in human cells, including chromosomal abnormalities and hyperrecombination. Here, we investigate delayed genome instability of cells exposed to UV radiation. We examined homologous recombination-mediated reactivation of a green fluorescent protein (GFP) gene in p53-proficient human cells. We observed an approximately 5-fold enhancement of delayed hyperrecombination (DHR) among cells surviving a low dose of UV-C (5 J/m2), revealed as mixed GFP+/- colonies. UV-B did not induce DHR at an equitoxic (75 J/m2) dose or a higher dose (150 J/m2). UV is known to induce delayed hypermutation associated with increased oxidative stress. We found that hypoxanthine phosphoribosyltransferase (HPRT) mutation frequencies were approximately 5-fold higher in strains derived from GFP+/- (DHR) colonies than in strains in which recombination was directly induced by UV (GFP+ colonies). To determine whether hypermutation was directly caused by hyperrecombination, we analyzed hprt mutation spectra. Large-scale alterations reflecting large deletions and insertions were observed in 25% of GFP+ strains, and most mutants had a single change in HPRT. In striking contrast, all mutations arising in the hypermutable GFP+/- strains were small (1- to 2-base) changes, including substitutions, deletions, and insertions (reminiscent of mutagenesis from oxidative damage), and the majority were compound, with an average of four hprt mutations per mutant. The absence of large hprt deletions in DHR strains indicates that DHR does not cause hypermutation. We propose that UV-induced DHR and hypermutation result from a common source, namely, increased oxidative stress. These two forms of delayed genome instability may collaborate in skin cancer initiation and progression. PMID:16880516

  7. Use of biomarkers for assessing radiation injury and efficacy of countermeasures

    PubMed Central

    Singh, Vijay K; Newman, Victoria L; Romaine, Patricia LP; Hauer-Jensen, Martin; Pollard, Harvey B

    2016-01-01

    Several candidate drugs for acute radiation syndrome (ARS) have been identified that have low toxicity and significant radioprotective and radiomitigative efficacy. Inasmuch as exposing healthy human volunteers to injurious levels of radiation is unethical, development and approval of new radiation countermeasures for ARS are therefore presently based on animal studies and Phase I safety study in healthy volunteers. The Animal Efficacy Rule, which underlies the Food and Drug Administration approval pathway, requires a sound understanding of the mechanisms of injury, drug efficacy, and efficacy biomarkers. In this context, it is important to identify biomarkers for radiation injury and drug efficacy that can extrapolate animal efficacy results, and can be used to convert drug doses deduced from animal studies to those that can be efficacious when used in humans. Here, we summarize the progress of studies to identify candidate biomarkers for the extent of radiation injury and for evaluation of countermeasure efficacy. PMID:26568096

  8. Cu, Fe, Mn, and Zn chelates offer a medicinal chemistry approach to overcoming radiation injury.

    PubMed

    Sorenson, John R J

    2002-03-01

    This review points out that treatment with essential metalloelement (Cu, Fe, Mn, and Zn) chelates facilitate tissue repair processes required for recovery from radiation injury including survival of lethally irradiated mice and rats. Results of studies pertaining to successful uses of bioavailable essential metalloelement chelates and combinations of them as well as aminothiols, Ca-channel blockers, acyl Melatonin homologs, substituted anilines, and curcumin radioprotectants are included in this review to suggest their use as chelates in overcoming radiation injury. Additional reports document that non-toxic doses of essential metalloelement chelates are effective in increasing survival and repairing radiation injury when administered before irradiation, in the radiation protection paradigm, and effective in increasing survival when used to treat after irradiation, in the radiorecovery paradigm. There are no other agents known to be effective in increasing survival when they are used to treat after irradiation. These approaches to radioprotection and radiorecovery offer promising approaches to facilitating recovery from radiation-induced injury experienced by patients undergoing radiation therapy for their neoplastic disease and by individuals who experience environmental, occupational, or accidental exposure to ionizing radiation. These individuals include those exposed to radiation resulting from nuclear accidents, the use of depleted uranium missiles, and astronauts undertaking space travel. Since there are no existing safe and effective treatments of radiation injury, studies of essential metalloelement chelates and combinations of them, as well as combinations of them with existing radioprotectant aminothiols, Ca-channel blockers, acyl Melatonin homologs, substituted anilines, and curcumin as radioprotectants seem worthwhile.

  9. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    PubMed

    Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  10. Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

    PubMed Central

    Jung, Enjae; Perrone, Erin E.; Brahmamdan, Pavan; McDonough, Jacquelyn S.; Leathersich, Ann M.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Hotchkiss, Richard S.; Coopersmith, Craig M.

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  11. Biophysical modelling of early and delayed radiation damage at chromosome level

    NASA Astrophysics Data System (ADS)

    Andreev, S.; Eidelman, Y.

    Exposure by ionising radiation increases cancer risk in human population Cancer is thought to originate from an altered expression of certain number of specific genes It is now widely recognised that chromosome aberrations CA are involved in stable change in expression of genes by gain or loss of their functions Thus CA can contribute to initiation or progression of cancer Therefore understanding mechanisms of CA formation in the course of cancer development might be valuable tool for quantification and prognosis of different stages of radiation carcinogenesis Early CA are defined as aberrations induced in first post-irradiation mitotic cycle The present work describes the original biophysical technique for early CA modelling It includes the following simulation steps the ionising particle track structure the structural organisation of all chromosomes in G 0 G 1 cell nucleus spatial distribution of radiation induced DNA double-strand breaks dsb within chromosomes dsb rejoining and misrejoining modelling cell cycle taking into account mitotic delay which results in complex time dependence of aberrant cells in first mitosis The results on prediction of dose-response curves for simple and complex CA measured in cells undergoing first division cycle are presented in comparison with recent experimental data There is increasing evidence that CA are also observed in descendents of irradiated cells many generations after direct DNA damage These delayed CA or chromosome instability CI are thought to be a manifestation of genome

  12. Reconstruction of radiation-induced injuries of the lower urinary tract.

    PubMed

    Ballek, Nathaniel K; Gonzalez, Christopher M

    2013-08-01

    This article presents an overview of reconstruction of lower urinary tract injury caused by radiation therapy for prostate cancer. Discussions include cause, patient evaluation, reconstructive techniques, and outcomes following repair.

  13. Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats

    PubMed Central

    Mahmood, J.; Jelveh, S.; Zaidi, A.; Doctrow, S. R.; Hill, R. P.

    2013-01-01

    Exposure of civilian populations to radiation due to accident, war or terrorist act is an increasing concern. The lung is one of the more radiosensitive organs that may be affected in people receiving partial-body irradiation and radiation injury in lung is thought to be associated with the development of a prolonged inflammatory response. Here we examined how effectively damage to the lung can be mitigated by administration of drugs initiated at different times after radiation exposure and examined response in adolescent animals for comparison with the young adult animals that we had studied previously. We studied the mitigation efficacy of the isoflavone genistein (50 mg/kg) and the salen-Mn superoxide dismutase-catalase mimetic EUK-207 (8 mg/kg), both of which have been reported to scavenge reactive oxygen species and reduce activity of the NFkB pathway. The drugs were given by subcutaneous injection to 6- to 7-week-old Fisher rats daily starting either immediately or 2 weeks after irradiation with 12 Gy to the whole thorax. The treatment was stopped at 28 weeks post irradiation and the animals were assessed for levels of inflammatory cytokines, activated macrophages, oxidative damage and fibrosis at 48 weeks post irradiation. We demonstrated that both genistein and EUK-207 delayed and suppressed the increased breathing rate associated with pneumonitis. These agents also reduced levels of oxidative damage (50–100%), levels of TGF-β1 expression (75–100%), activated macrophages (20–60%) and fibrosis (60–80%). The adolescent rats developed pneumonitis earlier following irradiation of the lung than did the adult rats leading to greater severe morbidity requiring euthanasia (~37% in adolescents vs. ~10% in young adults) but the extent of the mitigation of the damage was similar or slightly greater. PMID:23237541

  14. [Experimental model of severe local radiation injuries of the skin after X-rays].

    PubMed

    Kotenko, K V; Moroz, B B; Nasonova, T A; Dobrynina, O A; LIpengolz, A A; Gimadova, T I; Deshevoy, Yu B; Lebedev, V G; Lyrschikova, A V; Eremin, I I

    2013-01-01

    The experimental model of severe local radiation injuries skin under the influence of a relatively soft X-rays on a modified device RAP 100-10 produced by "Diagnostica-M" (Russia) was proposed. The model can be used as pre-clinical studies in small experimental animals in order to improve the treatment of local radiation injuries, especially in the conditions of application of cellular therapy.

  15. Nuclear terrorism: triage and medical management of radiation and combined-injury casualties.

    PubMed

    Flynn, Daniel F; Goans, Ronald E

    2006-06-01

    This article addresses the medical effects of nuclear explosions and other forms of radiation exposure, assessment of radiation dose, triage of victims, definitive treatment of radiation and combined-injury casualties, and planning for emergency services after a terrorist attack involving a nuclear device. It reviews historical events of mass radiation-induced casualties and fatalities at Hiroshima, Chernobyl, and Goiania, and discusses various scenarios for nuclear terrorism.

  16. Seat belt syndrome: Delayed or missed intestinal injuries, a case report and review of literature

    PubMed Central

    Al-Ozaibi, Labib; Adnan, Judy; Hassan, Batool; Al-Mazroui, Alya; Al-Badri, Faisal

    2016-01-01

    Introduction Seat belt injuries are not uncommon. The use of seat belts is associated with a unique injury profile collectively termed “the seat belt syndrome”. The aim is to aid in the early diagnosis of seat belt injuries. Case presentation Two different patients presented to the emergency after sustaining a motor vehicle accident. Both were the drivers, restrained and had a frontal impact. On presentation they were hemodynamically stable with mild tenderness on the abdomen and the abdominal computed tomography (CT) did not show any signs of bowel or mesenteric injuries. The signs of peritonitis became obvious after 24 h in one case and after 3 days in the other. Discussion Early diagnosis provides better outcomes for patients with seat belt injuries, but this remains a challenge to trauma surgeons. The typical findings of peritonitis might not be present initially. The presence of abdominal wall ecchymosis (seat belt sign) increases the chance of intraabdominal injuries by eight folds. Conclusion Clinical signs of intestinal injuries might not be obvious on presentation. In the presence of seat belt sign the possibility of bowl injury must be suspected. Admit the patient for observation even if no clinical or radiological findings are present at presentation. PMID:26826929

  17. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  18. Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats.

    PubMed

    Watanabe, Sadahiro; Fujita, Masanori; Ishihara, Masayuki; Tachibana, Shoichi; Yamamoto, Yoritsuna; Kaji, Tatsumi; Kawauchi, Toshio; Kanatani, Yasuhiro

    2014-11-01

    The effect of inhalation of hydrogen-containing gas (1.3% hydrogen + 20.8% oxygen + 77.9% nitrogen) (HCG) on radiation-induced dermatitis and on the healing of healing-impaired skin wounds in rats was examined using a rat model of radiation-induced skin injury. An X-ray dose of 20 Gy was irradiated onto the lower part of the back through two holes in a lead shield. Irradiation was performed before or after inhalation of HCG for 2 h. Inhalation of HCG significantly reduced the severity of radiodermatitis and accelerated healing-impaired wound repair. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and 8-hydroxy-2(')-deoxyguanosine (8-OHdG) showed that the proportion of apoptotic keratinocytes and the level of staining in the X-irradiated skin of rats that pre-inhaled HCG were significantly lower than that of rats which did not pre-inhale HCG. Cutaneous full-thickness wounds were then created in the X-irradiated area to examine the time-course of wound healing. X-irradiation significantly increased the time required for wound healing, but the inhalation of HCG prior to the irradiation significantly decreased the delay in wound healing compared with the control and post-inhalation of HCG groups. Therefore, radiation-induced skin injury can potentially be alleviated by the pre-inhalation of HCG.

  19. Delaying the onset of treadmill exercise following peripheral nerve injury has different effects on axon regeneration and motoneuron synaptic plasticity.

    PubMed

    Brandt, Jaclyn; Evans, Jonathan T; Mildenhall, Taylor; Mulligan, Amanda; Konieczny, Aimee; Rose, Samuel J; English, Arthur W

    2015-04-01

    Transection of a peripheral nerve results in withdrawal of synapses from motoneurons. Some of the withdrawn synapses are restored spontaneously, but those containing the vesicular glutamate transporter 1 (VGLUT1), and arising mainly from primary afferent neurons, are withdrawn permanently. If animals are exercised immediately after nerve injury, regeneration of the damaged axons is enhanced and no withdrawal of synapses from injured motoneurons can be detected. We investigated whether delaying the onset of exercise until after synapse withdrawal had occurred would yield similar results. In Lewis rats, the right sciatic nerve was cut and repaired. Reinnervation of the soleus muscle was monitored until a direct muscle (M) response was observed to stimulation of the tibial nerve. At that time, rats began 2 wk of daily treadmill exercise using an interval training protocol. Both M responses and electrically-evoked H reflexes were monitored weekly for an additional seven wk. Contacts made by structures containing VGLUT1 or glutamic acid decarboxylase (GAD67) with motoneurons were studied from confocal images of retrogradely labeled cells. Timing of full muscle reinnervation was similar in both delayed and immediately exercised rats. H reflex amplitude in delayed exercised rats was only half that found in immediately exercised animals. Unlike immediately exercised animals, motoneuron contacts containing VGLUT1 in delayed exercised rats were reduced significantly, relative to intact rats. The therapeutic window for application of exercise as a treatment to promote restoration of synaptic inputs onto motoneurons following peripheral nerve injury is different from that for promoting axon regeneration in the periphery. PMID:25632080

  20. Capabilities for Clinical Management of Radiation Injuries of the Nikiforov Russian Center of Emergency and Radiation Medicine (EMERCOM of Russia).

    PubMed

    Aleksanin, S

    2016-09-01

    This article presents an overview of the capabilities for clinical management of radiation injuries available at the Nikiforov Russian Center of Emergency and Radiation Medicine (NRCERM) of the Ministry of the Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters (EMERCOM). NRCERM is a federal state budgetary institution and the Russian Federation's head organization for providing medical assistance for persons overexposed to ionizing radiation, responders to radiation emergencies and people evacuated from radiation contaminated areas. As the WHO Collaborating Center for Treatment and Rehabilitation of Accident Recovery Workers of Nuclear and Other Disasters and a member of the WHO Radiation Emergency Medical Preparedness and Assistance Network (REMPAN), NRCERM is prepared to provide assistance and technical support in case of a radiation accident. For this purpose, NRCERM hospitals are equipped with technologically advanced facilities and possess well-trained specialist staff.

  1. Capabilities for Clinical Management of Radiation Injuries of the Nikiforov Russian Center of Emergency and Radiation Medicine (EMERCOM of Russia).

    PubMed

    Aleksanin, S

    2016-09-01

    This article presents an overview of the capabilities for clinical management of radiation injuries available at the Nikiforov Russian Center of Emergency and Radiation Medicine (NRCERM) of the Ministry of the Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters (EMERCOM). NRCERM is a federal state budgetary institution and the Russian Federation's head organization for providing medical assistance for persons overexposed to ionizing radiation, responders to radiation emergencies and people evacuated from radiation contaminated areas. As the WHO Collaborating Center for Treatment and Rehabilitation of Accident Recovery Workers of Nuclear and Other Disasters and a member of the WHO Radiation Emergency Medical Preparedness and Assistance Network (REMPAN), NRCERM is prepared to provide assistance and technical support in case of a radiation accident. For this purpose, NRCERM hospitals are equipped with technologically advanced facilities and possess well-trained specialist staff. PMID:27664998

  2. Radiation injury after a nuclear detonation: medical consequences and the need for scarce resources allocation.

    PubMed

    DiCarlo, Andrea L; Maher, Carmen; Hick, John L; Hanfling, Dan; Dainiak, Nicholas; Chao, Nelson; Bader, Judith L; Coleman, C Norman; Weinstock, David M

    2011-03-01

    A 10-kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network. PMID:21402810

  3. Radiation Injury After a Nuclear Detonation: Medical Consequences and the Need for Scarce Resources Allocation

    PubMed Central

    DiCarlo, Andrea L.; Maher, Carmen; Hick, John L.; Hanfling, Dan; Dainiak, Nicholas; Chao, Nelson; Bader, Judith L.; Coleman, C. Norman; Weinstock, David M.

    2013-01-01

    A 10-kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network. PMID:21402810

  4. Three-phase radionuclide bone scanning in evaluation of local radiation injury. A case report

    SciTech Connect

    Mettler, F.A. Jr.; Monsein, L.; Davis, M.; Rosenberg, R.; Kelsey, C.; Listrom, M.

    1987-10-01

    The management of local radiation injuries is influenced by the degree of vascular compromise within the skin and underlying tissues. Other authors have used thermography and angiography in assessing the blood flow to radiation damaged tissues. This report describes the use of radionuclide imaging in the evaluation of a patient who developed necrosis of his distal digits following a radiation accident. In addition to determining the vascular status of the hands, imaging helped indicate an appropriate level for amputation.

  5. Delayed Workforce Entry and High Emigration Rates for Recent Canadian Radiation Oncology Graduates

    SciTech Connect

    Loewen, Shaun K.; Halperin, Ross; Lefresne, Shilo; Trotter, Theresa; Stuckless, Teri; Brundage, Michael

    2015-10-01

    Purpose: To determine the employment status and location of recent Canadian radiation oncology (RO) graduates and to identify current workforce entry trends. Methods and Materials: A fill-in-the-blank spreadsheet was distributed to all RO program directors in December 2013 and June 2014, requesting the employment status and location of their graduates over the last 3 years. Visa trainee graduates were excluded. Results: Response rate from program directors was 100% for both survey administrations. Of 101 graduates identified, 99 (98%) had known employment status and location. In the December survey, 5 2013 graduates (16%), 17 2012 graduates (59%), and 18 2011 graduates (75%) had permanent staff employment. Six months later, 5 2014 graduates (29%), 15 2013 graduates (48%), 24 2012 graduates (83%), and 21 2011 graduates (88%) had secured staff positions. Fellowships and temporary locums were common for those without staff employment. The proportion of graduates with staff positions abroad increased from 22% to 26% 6 months later. Conclusions: Workforce entry for most RO graduates was delayed but showed steady improvement with longer time after graduation. High emigration rates for jobs abroad signify domestic employment challenges for newly certified, Canadian-trained radiation oncologists. Coordination on a national level is required to address and regulate radiation oncologist supply and demand disequilibrium in Canada.

  6. Thermal Injury Lowers the Threshold for Radiation-Induced Neuroinflammation and Cognitive Dysfunction

    PubMed Central

    Cherry, Jonathan D.; Williams, Jacqueline P.; O’Banion, M. Kerry; Olschowka, John A.

    2013-01-01

    The consequences of radiation exposure alone are relatively well understood, but in the wake of events such as the World War II nuclear detonations and accidents such as Chernobyl, other critical factors have emerged that can substantially affect patient outcome. For example, ~70% of radiation victims from Hiroshima and Nagasaki received some sort of additional traumatic injury, the most common being thermal burn. Animal data has shown that the addition of thermal insult to radiation results in increased morbidity and mortality. To explore possible synergism between thermal injury and radiation on brain, C57BL/6J female mice were exposed to either 0 or 5 Gy whole-body gamma irradiation. Irradiation was immediately followed by a 10% total-body surface area full thickness thermal burn. Mice were sacrificed 6 h, 1 week or 6 month post-injury and brains and plasma were harvested for histology, mRNA analysis and cytokine ELISA. Plasma analysis revealed that combined injury synergistically upregulates IL-6 at acute time points. Additionally, at 6 h, combined injury resulted in a greater upregulation of the vascular marker, ICAM-1 and TNF-α mRNA. Enhanced activation of glial cells was also observed by CD68 and Iba1 immunohistochemistry at all time points. Additionally, doublecortin staining at 6 months showed reduced neurogenesis in all injury conditions. Finally, using a novel object recognition test, we observed that only mice with combined injury had significant learning and memory deficits. These results demonstrate that thermal injury lowers the threshold for radiation-induced neuroinflammation and long-term cognitive dysfunction. PMID:24059681

  7. New strategies for the prevention of radiation injury: possible implications for countering radiation hazards of long-term space travel.

    PubMed

    Seed, Thomas; Kumar, Sree; Whitnall, Mark; Srinivasan, Venkataraman; Singh, Vijay; Elliott, Thomas; Landauer, Michael; Miller, Alexandra; Chang, Cheng-Min; Inal, Cyndi; Deen, Jason; Gehlhaus, Martin; Jackson, William; Hilyard, Edward; Pendergrass, James; Toles, Raymond; Villa, Vilmar; Miner, Venita; Stewart, Michael; Benjack, James; Danilenko, Dimitry; Farrell, Ckatherine

    2002-12-01

    New strategies for the prevention of radiation injuries are currently being explored with the ultimate aim of developing globally radioprotective, nontoxic pharmacologics. The prophylactic treatments under review encompass such diverse pharmacologic classes as novel immunomodulators, nutritional antioxidants, and cytokines. An immunomodulator that shows promise is 5-androstenediol (AED), a well-tolerated, long-acting androstene steroid with broad-spectrum radioprotective attributes that include not only protection against acute tissue injury, but also reduced susceptibility to infectious agents, as well as reduced rates of neoplastic transformation. Other potentially useful radioprotectants currently under study include the nutraceutical vitamin E and analogs, a chemically-engineered cytokine, interleukin-1beta, and a sustained-release formulation of an aminothiol, amifostine. Results suggest that a new paradigm is evolving for the prophylaxes of radiation injuries, based on use of newly identified, nontoxic, broad-spectrum prophylactic agents whose protective action may be leveraged by subsequent postexposure use of cytokines with organ-specific reparative functions.

  8. Preference for Progressive Delays and Concurrent Physical Therapy Exercise in an Adult with Acquired Brain Injury

    ERIC Educational Resources Information Center

    Dixon, Mark R.; Falcomata, Terry S.

    2004-01-01

    The purpose of this study was to increase self-control and engagement in a physical therapy task (head holding) for a man with acquired traumatic brain injury. Once impulsivity was observed (i.e., repeated impulsive choices), an experimental condition was introduced that consisted of choices between a small immediate reinforcer, a large…

  9. Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice

    PubMed Central

    Li, Ming; Du, Aonan; Xu, Jing; Ma, Yanchao; Cao, Han; Yang, Chao; Yang, Xiao-Dong; Xing, Chun-Gen; Chen, Ming; Zhu, Wei; Zhang, Shuyu; Cao, Jianping

    2016-01-01

    The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation, and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein, and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis, and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury, and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure. PMID:27436572

  10. Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

    PubMed Central

    Acharya, Sanket S.; Fendler, Wojciech; Watson, Jacqueline; Hamilton, Abigail; Pan, Yunfeng; Gaudiano, Emily; Moskwa, Patryk; Bhanja, Payel; Saha, Subhrajit; Guha, Chandan; Parmar, Kalindi; Chowdhury, Dipanjan

    2015-01-01

    Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation. PMID:25972001

  11. Protection from radiation injury by elemental diet: does added glutamine change the effect?

    PubMed

    McArdle, A H

    1994-01-01

    The feeding of a protein hydrolysate based 'elemental' diet supplemented with added glutamine did not provide superior protection to the small intestine of dogs subjected to therapeutic pelvic irradiation. Comparison of diets with and without the added glutamine showed significant protection of the intestine from radiation injury. Both histological examination and electron microscopy showed lack of tissue injury with both diets. The activity of the free radical generating enzymes, scavengers, and antioxidants were similar in the intestinal mucosa of dogs fed either diet. After radiation, however, the activity of xanthine oxidase, superoxide dismutase, and glutathione peroxidase were significantly (p < 0.002) higher in the intestine of dogs fed elemental diet without the added glutamine. If the activities of these enzymes are important in the protection of the intestine from radiation injury, then the addition of extra glutamine may provide no benefit.

  12. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

  13. Radiation Dose-Volume Effects in Radiation-Induced Rectal Injury

    SciTech Connect

    Michalski, Jeff M.; Gay, Hiram; Jackson, Andrew; Tucker, Susan L.; Deasy, Joseph O.

    2010-03-01

    The available dose/volume/outcome data for rectal injury were reviewed. The volume of rectum receiving >=60Gy is consistently associated with the risk of Grade >=2 rectal toxicity or rectal bleeding. Parameters for the Lyman-Kutcher-Burman normal tissue complication probability model from four clinical series are remarkably consistent, suggesting that high doses are predominant in determining the risk of toxicity. The best overall estimates (95% confidence interval) of the Lyman-Kutcher-Burman model parameters are n = 0.09 (0.04-0.14); m = 0.13 (0.10-0.17); and TD{sub 50} = 76.9 (73.7-80.1) Gy. Most of the models of late radiation toxicity come from three-dimensional conformal radiotherapy dose-escalation studies of early-stage prostate cancer. It is possible that intensity-modulated radiotherapy or proton beam dose distributions require modification of these models because of the inherent differences in low and intermediate dose distributions.

  14. Blood brain barrier dysfunction and delayed neurological deficits in mild traumatic brain injury induced by blast shock waves

    PubMed Central

    Shetty, Ashok K.; Mishra, Vikas; Kodali, Maheedhar; Hattiangady, Bharathi

    2014-01-01

    Mild traumatic brain injury (mTBI) resulting from exposure to blast shock waves (BSWs) is one of the most predominant causes of illnesses among veterans who served in the recent Iraq and Afghanistan wars. Such mTBI can also happen to civilians if exposed to shock waves of bomb attacks by terrorists. While cognitive problems, memory dysfunction, depression, anxiety and diffuse white matter injury have been observed at both early and/or delayed time-points, an initial brain pathology resulting from exposure to BSWs appears to be the dysfunction or disruption of the blood-brain barrier (BBB). Studies in animal models suggest that exposure to relatively milder BSWs (123 kPa) initially induces free radical generating enzymes in and around brain capillaries, which enhances oxidative stress resulting in loss of tight junction (TJ) proteins, edema formation, and leakiness of BBB with disruption or loss of its components pericytes and astrocyte end-feet. On the other hand, exposure to more intense BSWs (145–323 kPa) causes acute disruption of the BBB with vascular lesions in the brain. Both of these scenarios lead to apoptosis of endothelial and neural cells and neuroinflammation in and around capillaries, which may progress into chronic traumatic encephalopathy (CTE) and/or a variety of neurological impairments, depending on brain regions that are afflicted with such lesions. This review discusses studies that examined alterations in the brain milieu causing dysfunction or disruption of the BBB and neuroinflammation following exposure to different intensities of BSWs. Furthermore, potential of early intervention strategies capable of easing oxidative stress, repairing the BBB or blocking inflammation for minimizing delayed neurological deficits resulting from exposure to BSWs is conferred. PMID:25165433

  15. Blood brain barrier dysfunction and delayed neurological deficits in mild traumatic brain injury induced by blast shock waves.

    PubMed

    Shetty, Ashok K; Mishra, Vikas; Kodali, Maheedhar; Hattiangady, Bharathi

    2014-01-01

    Mild traumatic brain injury (mTBI) resulting from exposure to blast shock waves (BSWs) is one of the most predominant causes of illnesses among veterans who served in the recent Iraq and Afghanistan wars. Such mTBI can also happen to civilians if exposed to shock waves of bomb attacks by terrorists. While cognitive problems, memory dysfunction, depression, anxiety and diffuse white matter injury have been observed at both early and/or delayed time-points, an initial brain pathology resulting from exposure to BSWs appears to be the dysfunction or disruption of the blood-brain barrier (BBB). Studies in animal models suggest that exposure to relatively milder BSWs (123 kPa) initially induces free radical generating enzymes in and around brain capillaries, which enhances oxidative stress resulting in loss of tight junction (TJ) proteins, edema formation, and leakiness of BBB with disruption or loss of its components pericytes and astrocyte end-feet. On the other hand, exposure to more intense BSWs (145-323 kPa) causes acute disruption of the BBB with vascular lesions in the brain. Both of these scenarios lead to apoptosis of endothelial and neural cells and neuroinflammation in and around capillaries, which may progress into chronic traumatic encephalopathy (CTE) and/or a variety of neurological impairments, depending on brain regions that are afflicted with such lesions. This review discusses studies that examined alterations in the brain milieu causing dysfunction or disruption of the BBB and neuroinflammation following exposure to different intensities of BSWs. Furthermore, potential of early intervention strategies capable of easing oxidative stress, repairing the BBB or blocking inflammation for minimizing delayed neurological deficits resulting from exposure to BSWs is conferred. PMID:25165433

  16. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats.

    PubMed

    Bakkal, B H; Gultekin, F A; Guven, B; Turkcu, U O; Bektas, S; Can, M

    2013-09-01

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  17. The biological effect of prolonged radiation and ways of selecting new anti-radiation drugs effective in this kind of radiation injury

    NASA Technical Reports Server (NTRS)

    Rogozkin, V. D.; Chertkov, K. S.; Nikolov, I.

    1974-01-01

    The basic characteristics of prolonged radiation - increased tolerance of radiation injury - are attributed to cellular kinetics; as dose rate is reduced, the population rate is not disturbed, particularly that of stem cells which makes it possible for the organism to tolerate higher radiation loads. It is concluded that this effect makes approved radio protectors, whose effect contains an established cytostatic component, unsuitable for prolonged radiation. It is better to correct the stem pool formation process by either accelerating the proliferation of cells or limiting the effect of stimuli causing cells to lose colony forming properties.

  18. Relief of delayed oxidative stress by ascorbic acid can suppress radiation-induced cellular senescence in mammalian fibroblast cells.

    PubMed

    Kobashigawa, Shinko; Kashino, Genro; Mori, Hiromu; Watanabe, Masami

    2015-03-01

    Ionizing radiation-induced cellular senescence is thought to be caused by nuclear DNA damage that cannot be repaired. However, here we found that radiation induces delayed increase of intracellular oxidative stress after irradiation. We investigated whether the relief of delayed oxidative stress by ascorbic acid would suppress the radiation-induced cellular senescence in Syrian golden hamster embryo (SHE) cells. We observed that the level of oxidative stress was drastically increased soon after irradiation, then declined to the level in non-irradiated cells, and increased again with a peak on day 3 after irradiation. We found that the inductions of cellular senescence after X-irradiation were reduced along with suppression of the delayed induction of oxidative stress by treatment with ascorbic acid, but not when oxidative stress occurred immediately after irradiation. Moreover, treatment of ascorbic acid inhibited p53 accumulation at 3 days after irradiation. Our data suggested a delayed increase of intracellular oxidative stress levels plays an important role in the process of radiation-induced cellular senescence by p53 accumulation.

  19. Complement Modulation of Anti-Aging Factor Klotho in Ischemia/Reperfusion Injury and Delayed Graft Function.

    PubMed

    Castellano, G; Intini, A; Stasi, A; Divella, C; Gigante, M; Pontrelli, P; Franzin, R; Accetturo, M; Zito, A; Fiorentino, M; Montinaro, V; Lucarelli, G; Ditonno, P; Battaglia, M; Crovace, A; Staffieri, F; Oortwijn, B; van Amersfoort, E; Pertosa, G; Grandaliano, G; Gesualdo, L

    2016-01-01

    Klotho is an anti-aging factor mainly produced by renal tubular epithelial cells (TEC) with pleiotropic functions. Klotho is down-regulated in acute kidney injury in native kidney; however, the modulation of Klotho in kidney transplantation has not been investigated. In a swine model of ischemia/reperfusion injury (IRI), we observed a remarkable reduction of renal Klotho by 24 h from IRI. Complement inhibition by C1-inhibitor preserved Klotho expression in vivo by abrogating nuclear factor kappa B (NF-kB) signaling. In accordance, complement anaphylotoxin C5a led to a significant down-regulation of Klotho in TEC in vitro that was NF-kB mediated. Analysis of Klotho in kidneys from cadaveric donors demonstrated a significant expression of Klotho in pre-implantation biopsies; however, patients affected by delayed graft function (DGF) showed a profound down-regulation of Klotho compared with patients with early graft function. Quantification of serum Klotho after 2 years from transplantation demonstrated significant lower levels in DGF patients. Our data demonstrated that complement might be pivotal in the down-regulation of Klotho in IRI leading to a permanent deficiency after years from transplantation. Considering the anti-senescence and anti-fibrotic effects of Klotho at renal levels, we hypothesize that this acquired deficiency of Klotho might contribute to DGF-associated chronic allograft dysfunction.

  20. Complement Modulation of Anti-Aging Factor Klotho in Ischemia/Reperfusion Injury and Delayed Graft Function.

    PubMed

    Castellano, G; Intini, A; Stasi, A; Divella, C; Gigante, M; Pontrelli, P; Franzin, R; Accetturo, M; Zito, A; Fiorentino, M; Montinaro, V; Lucarelli, G; Ditonno, P; Battaglia, M; Crovace, A; Staffieri, F; Oortwijn, B; van Amersfoort, E; Pertosa, G; Grandaliano, G; Gesualdo, L

    2016-01-01

    Klotho is an anti-aging factor mainly produced by renal tubular epithelial cells (TEC) with pleiotropic functions. Klotho is down-regulated in acute kidney injury in native kidney; however, the modulation of Klotho in kidney transplantation has not been investigated. In a swine model of ischemia/reperfusion injury (IRI), we observed a remarkable reduction of renal Klotho by 24 h from IRI. Complement inhibition by C1-inhibitor preserved Klotho expression in vivo by abrogating nuclear factor kappa B (NF-kB) signaling. In accordance, complement anaphylotoxin C5a led to a significant down-regulation of Klotho in TEC in vitro that was NF-kB mediated. Analysis of Klotho in kidneys from cadaveric donors demonstrated a significant expression of Klotho in pre-implantation biopsies; however, patients affected by delayed graft function (DGF) showed a profound down-regulation of Klotho compared with patients with early graft function. Quantification of serum Klotho after 2 years from transplantation demonstrated significant lower levels in DGF patients. Our data demonstrated that complement might be pivotal in the down-regulation of Klotho in IRI leading to a permanent deficiency after years from transplantation. Considering the anti-senescence and anti-fibrotic effects of Klotho at renal levels, we hypothesize that this acquired deficiency of Klotho might contribute to DGF-associated chronic allograft dysfunction. PMID:26280899

  1. Electromechanical delay of the hamstrings during eccentric muscle actions in males and females: Implications for non-contact ACL injuries.

    PubMed

    De Ste Croix, Mark B A; ElNagar, Youssif O; Iga, John; James, David; Ayala, Francisco

    2015-12-01

    Sex differences in neuromuscular functioning has been proposed as one of the factors behind an increased relative risk of non-contact anterior cruciate ligament (ACL) injury in females. The aim of this study was to explore sex differences in electromechanical delay (EMD) of the hamstring muscles during eccentric muscle actions and during a range of movement velocities. This study recruited 110 participants (55 males, 55 females) and electromyography of the semitendinosus, semimembranosus and biceps femoris was determined during eccentric actions at 60, 120 and 240°/s. No significant sex differences were observed irrespective of muscle examined or movement velocity. Irrespective of sex EMD significantly increased with increasing movement velocity (P < 0.01). There was no significant difference in the EMD of the 3 muscles examined. Our findings suggest that during eccentric actions of the hamstrings that there are no sex differences, irrespective of movement velocity. This would suggest that other factors are probably responsible for the increased relative risk of non-contact ACL injury in females compared to males. PMID:26522999

  2. Delayed rehabilitation lessens brain injury and improves recovery after intracerebral hemorrhage in rats.

    PubMed

    Auriat, Angela M; Colbourne, Frederick

    2009-01-28

    Rehabilitation improves recovery after intracerebral hemorrhage (ICH) in rats. In some cases, brain damage is attenuated. In this study, we tested whether environmental enrichment (EE) combined with skilled reach training improves recovery and lessens brain injury after ICH in rats. Collagenase was injected stereotaxically to produce a moderate-sized striatal ICH. One week after ICH rats were either placed into a rehabilitation (REHAB) or control (CONT) condition. The REHAB rats received 15 h of EE and four 15-minute reach-training sessions daily over 5 days a week for 2 weeks. The CONT rats stayed in standard group cages. Skilled reaching (staircase test), walking (horizontal ladder) and forelimb use bias (cylinder test) were assessed at 4 and 6 weeks after ICH. Lesion volume, corpus callosum volume and cortical thickness were calculated 46 days after ICH. The REHAB treatment reduced lesion volume by 28% (p=0.019) without affecting the corpus callosum volume (p=0.405) or cortical thickness (p=0.300), thus indicating that protection was due to lessening striatal injury. As well, REHAB significantly improved skilled reaching ability in the staircase apparatus at 4 (p=0.002) and 6 weeks (p<0.001) post-ICH. Transient benefit was obtained in the ladder test at 4 weeks (p=0.021). Unexpectedly, REHAB treatment lessened spontaneous use of the contralateral-to-ICH limb at 4 (p=0.045) and 6 weeks (p=0.041). In summary, the combination of EE and reach training significantly attenuates lesion volume (striatal injury) while improving skilled reaching and walking ability. These findings encourage the use of early rehabilitation therapies in patients suffering from basal ganglia hemorrhaging. PMID:19059222

  3. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    SciTech Connect

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro; and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  4. A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain.

    PubMed

    Dabjan, Mohamad B; Buck, Carolyn Ms; Jackson, Isabel L; Vujaskovic, Zeljko; Marples, Brian; Down, Julian D

    2016-09-01

    Within this millennium there has been resurgence in funding and research dealing with animal models of radiation-induced lung injury to identify and establish predictive biomarkers and effective mitigating agents that are applicable to humans. Most have been performed on mice but there needs to be assurance that the emphasis on such models is not misplaced. We therefore considered it timely to perform a comprehensive appraisal of the literature dealing with radiation lung injury of mice and to critically evaluate the validity and clinical relevance of the research. A total of 357 research papers covering the period of 1970-2015 were extensively reviewed. Whole thorax irradiation (WTI) has become the most common treatment for studying lung injury in mice and distinct trends were seen with regard to the murine strain, radiation dose, intended pathology investigated, length of study, and assays. Recently, the C57BL/6 strain has been increasingly used in the majority of these studies with the notion that they are susceptible to pulmonary fibrosis. Nonetheless, many of these investigations depend on animal survival as the primary end point and neglect the importance of radiation pneumonitis and the anomaly of lethal pleural effusions. A relatively large variation in survival times of C5BL/6 mice is also seen among different institutions pointing to the need for standardization of radiation treatments and environmental conditions. An analysis of mitigating drug treatments is complicated by the fact that the majority of studies are limited to the C57BL/6 strain with a premature termination of the experiments and do not establish whether the treatment actually prevents or simply delays the progression of radiation injury. This survey of the literature has pointed to several improvements that need to be considered in establishing a reliable preclinical murine model of radiation lung injury. The lethality end point should also be used cautiously and with greater emphasis on

  5. Optical Spectroscopy and Multivariate Analysis for Biodosimetry and Monitoring of Radiation Injury to the Skin

    SciTech Connect

    Levitskaia, Tatiana G.; Bryan, Samuel A.; Creim, Jeffrey A.; Curry, Terry L.; Luders, Teresa; Thrall, Karla D.; Peterson, James M.

    2012-08-01

    In the event of an intentional or accidental release of ionizing radiation in a densely populated area, timely assessment and triage of the general population for the radiation exposure is critical. In particular, a significant number of the victims may sustain cutaneous radiation injury, which increases the mortality and worsens the overall prognosis of the victims suffered from combined thermal/mechanical and radiation trauma. Diagnosis of the cutaneous radiation injury is challenging, and established methods largely rely on visual manifestations, presence of the skin contamination, and a high degree of recall by the victim. Availability of a high throughput non-invasive in vivo biodosimetry tool for assessment of the radiation exposure of the skin is of particular importance for the timely diagnosis of the cutaneous injury. In the reported investigation, we have tested the potential of an optical reflectance spectroscopy for the evaluation of the radiation injury to the skin. This is technically attractive because optical spectroscopy relies on well-established and routinely used for various applications instrumentation, one example being pulse oximetry which uses selected wavelengths for the quantification of the blood oxygenation. Our method relies on a broad spectral region ranging from the locally absorbed, shallow-penetrating ultraviolet and visible (250 to 800 nm) to more deeply penetrating near-Infrared (800 – 1600 nm) light for the monitoring of multiple physiological changes in the skin upon irradiation. Chemometrics is a multivariate methodology that allows the information from entire spectral region to be used to generate predictive regression models. In this report we demonstrate that simple spectroscopic method, such as the optical reflectance spectroscopy, in combination with multivariate data analysis, offers the promise of rapid and non-invasive in vivo diagnosis and monitoring of the cutaneous radiation exposure, and is able accurately predict

  6. Oxidative Stress Mediates Radiation Lung Injury by Inducing Apoptosis

    SciTech Connect

    Zhang Yu; Zhang Xiuwu; Rabbani, Zahid N.; Jackson, Isabel L.; Vujaskovic, Zeljko

    2012-06-01

    Purpose: Apoptosis in irradiated normal lung tissue has been observed several weeks after radiation. However, the signaling pathway propagating cell death after radiation remains unknown. Methods and Materials: C57BL/6J mice were irradiated with 15 Gy to the whole thorax. Pro-apoptotic signaling was evaluated 6 weeks after radiation with or without administration of AEOL10150, a potent catalytic scavenger of reactive oxygen and nitrogen species. Results: Apoptosis was observed primarily in type I and type II pneumocytes and endothelium. Apoptosis correlated with increased PTEN expression, inhibition of downstream PI3K/AKT signaling, and increased p53 and Bax protein levels. Transforming growth factor-{beta}1, Nox4, and oxidative stress were also increased 6 weeks after radiation. Therapeutic administration of AEOL10150 suppressed pro-apoptotic signaling and dramatically reduced the number of apoptotic cells. Conclusion: Increased PTEN signaling after radiation results in apoptosis of lung parenchymal cells. We hypothesize that upregulation of PTEN is influenced by Nox4-derived oxidative stress. To our knowledge, this is the first study to highlight the role of PTEN in radiation-induced pulmonary toxicity.

  7. Intestinal Microbiota Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    PubMed Central

    Broin, Pilib Ó; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I.; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J.; Guha, Chandan; Golden, Aaron

    2014-01-01

    Purpose Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials Groups of C57BL/6 mice (n=12 per group) were exposed to 0 Gy, 2 Gy, 4 Gy, 8 Gy, and 10.4 Gy of whole-body γ-radiation. At 24 hours post treatment all animals were euthanized and both plasma and liver biopsies obtained - the latter being used to deconvolve a distinct hepatic radiation injury response within plasma. A semi-quantitative untargeted metabolites/lipid profiling using both GC/MS and LC/MS/MS platforms was performed and identified 354 biochemicals. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence to indicate that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusion Plasma profiling of specific metabolites related to the pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites in particular represent an attractive marker for radiation injury within blood plasma. PMID:25636760

  8. Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    SciTech Connect

    Ó Broin, Pilib; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I.; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J.; Guha, Chandan; Golden, Aaron

    2015-02-01

    Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.

  9. Radiation Injury Treatment Network (RITN): Healthcare professionals preparing for a mass casualty radiological or nuclear incident

    PubMed Central

    ROSS, JOEL R.; CASE, CULLEN; CONFER, DENNIS; WEISDORF, DANIEL J.; WEINSTOCK, DAVID; KRAWISZ, ROBERT; CHUTE, JOHN; WILHAUK, JULIE; NAVARRO, WILLIS; HARTZMAN, ROBERT; COLEMAN, C. NORMAN; HATCHETT, RICHARD; CHAO, NELSON

    2011-01-01

    Purpose To describe the history, composition, and activities of the Radiation Injury Treatment Network (RITN). The Radiation Injury Treatment Network® is a cooperative effort of the National Marrow Donor Program and the American Society for Blood and Marrow Transplantation. The goals of RITN are to educate hematologists, oncologists, and stem cell transplant practitioners about their potential involvement in the response to a radiation incident and provide treatment expertise. Injuries to the marrow system readily occur when a victim is exposed to ionising radiation. This focus therefore leverages the expertise of these specialists who are accustomed to providing the intensive supportive care required by patients with a suppressed marrow function. Following a radiological incident, RITN centres may be asked to: Accept patient transfers to their institutions; provide treatment expertise to practitioners caring for victims at other centres; travel to other centres to provide medical expertise; or provide data on victims treated at their centres. Moving forward, it is crucial that we develop a coordinated interdisciplinary approach in planning for and responding to radiological and nuclear incidents. The ongoing efforts of radiation biologists, radiation oncologists, and health physicists can and should complement the efforts of RITN and government agencies. Conclusion RITN serves as a vital partner in preparedness and response efforts for potential radiological and nuclear incidents. PMID:21801106

  10. Time delays in the nonthermal radiation of solar flares according to observations of the CORONAS-F satellite

    NASA Astrophysics Data System (ADS)

    Tsap, Yu. T.; Stepanov, A. V.; Kashapova, L. K.; Myagkova, I. N.; Bogomolov, A. V.; Kopylova, Yu. G.; Goldvarg, T. B.

    2016-07-01

    In 2001-2003, the X-ray and microwave observations of ten solar flares of M- and X-classes were carried out by the CORONAS-F orbital station, the RSTN Sun service, and Nobeyama radio polarimeters. Based on these observations, a correlation analysis of time profiles of nonthermal radiation was performed. On average, hard X-ray radiation outstrips the microwave radiation in 9 events, i.e., time delays are positive. The appearance of negative delays is associated with effective scattering of accelerated electrons in pitch angles, where the length of the free path of a particle is less than the half-length of a flare loop. The additional indications are obtained in favor of the need to account for the effect of magnetic mirrors on the dynamics of energetic particles in the coronal arches.

  11. Use of iron colloid-enhanced MRI for study of acute radiation-induced hepatic injury

    SciTech Connect

    Suto, Yuji; Ametani, Masaki; Kato, Takashi; Hashimoto, Masayuki; Kamba, Masayuki; Sugihara, Syuji; Ohta, Yoshio

    1996-03-01

    We present a case with acute radiation-induced hepatic injury using chondroitin sulfate iron colloid (CSIC)-enhanced MRI. Uptake of CSIC was decreased in the irradiated portion of the liver. CSIC-enhanced MRI is useful for obtaining information on the function of the reticuloendothelial system and demarcates between irradiated and nonirradiated zones. 18 refs., 3 figs

  12. Good outcome after delayed surgery for orbitocranial non-missile penetrating brain injury.

    PubMed

    Caporlingua, Alessandro; Caporlingua, Federico; Lenzi, Jacopo

    2016-01-01

    Nonmissile orbitocranial penetrating brain injuries are uncommonly dealt with in a civilian context. Surgical management is controversial, due to the lack of widely accepted guidelines. A 52-year-old man was hit in his left eye by a metallic foreign body (FB). Head computed tomography (CT) scan showed a left subcortical parietal FB with a considerable hemorrhagic trail originating from the left orbital roof. Surgical treatment was staged; an exenteratio oculi and a left parietal craniotomy to extract the FB under intraoperative CT guidance were performed at post trauma day third and sixth, respectively. A postoperative infectious complication was treated conservatively. The patient retained a right hemiparesis (3/5) and was transferred to rehabilitation in good clinical conditions at day 49(th). He had suspended antiepilectic therapy at that time. A case-by-case tailored approach is mandatory to achieve the best outcome in such a heterogeneous nosological entity. Case reporting is crucial to further understand its mechanism and dynamics.

  13. Modulation with cytokines of radiation injury: suggested mechanisms of action.

    PubMed Central

    Neta, R

    1997-01-01

    Cytokines, hormonelike proteins, produced by stimulated cells and tissues, were found to protect mice against lethal hematopoietic failure caused by ionizing radiation. Radioprotection was achieved by pretreatment with interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-12, or stem cell factor (SCF) at 18 to 24 hr before irradiation. Pretreatment with antibodies to these cytokines rendered the mice more susceptible to radiation lethality, indicating that these cytokines play a role in innate resistance to radiation. In contrast, treatment with tumor growth factor beta (TGF-beta), a cytokine that inhibits cycling of primitive hematopoietic progenitors, sensitized mice to radiation lethality. The schedule of IL-1 administration was critical to its radioprotective effect. Evidence was obtained that this may be based on the induction of additional cytokines by IL-1. The radioprotective effects of cytokines can be based on induction of cycling of primitive progenitor cells (IL-1, SCF), prevention of apoptosis (SCF), and induction of scavenging proteins and enzymes (IL-1, TNF) that reduce oxidative damage. In contrast, radiosensitizing effects may be due to inhibition of progenitor cycling (TGF-beta) or enhanced progenitor cell apoptosis (TGF-beta). Thus, the insights gained from such studies at the whole-animal level promise a better understanding of the membrane and intracellular events associated with radiation damage and repair of such damage. PMID:9467064

  14. Future directions in therapy of whole body radiation injury

    SciTech Connect

    Cronkite, E.P.

    1989-01-01

    Clinicians have long known that marked granulocytopenia predisposed patients to bacterial infections either from pathogens or commensal organisms with which an individual usually lives in harmony. Evidence that infection was of major importance derives from several observations: (a) clinical observations of bacterial infection in human beings exposed to atomic bomb radiation in Hiroshima and Nagasaki, in reactor accidents, and in large animals dying from radiation exposure, (b) correlative studies on mortality rate, time of death, and incidence of positive culture in animals, (c) challenge of irradiated animals with normally non-virulent organisms, (d) studies of germ free mice and rats, and (e) studies of the effectiveness of antibiotics in reducing mortality rate. General knowledge and sound experimental data on animals and man clearly demonstrated that the sequelae of pancytopenia (bacterial infection, thrombopenic hemorrhage, and anemia) are the lethal factors. A lot of research was required to demonstrate that there were no mysterious radiations toxins, that hyperheparinemia was not a cause of radiation hemorrhage and that radiation hemorrhage could be prevented by fresh platelet transfusions.

  15. Radiation injury and acute death in Armadillidium vulgare (terrestrial isopod, Crustacea) subjected to ionizing radiation. [/sup 137/Cs

    SciTech Connect

    Nakatsuchi, Y.; Egami, N.

    1981-01-01

    From whole- and partial-body irradiation experiments with adult Armadillidium vulgare, the following conclusions were drawn: the LD/sub 50/-30 days for this animal when subjected to ..gamma.. radiation at 25 +- 2/sup 0/C was about 30 kR. Radiosensitivity of the animal changed during the molt cycle. Ionizing radiation increased mortality at ecdysis and during intermolt stages. Anatomical and histological observations indicated that (1) gastrointestinal injury as the major cause of acute death does not apply to this animal because the intestine is not a cell-proliferative organ: (2) the epidermis may be the critical target organ.

  16. Detection of microvasculature alterations by synchrotron radiation in murine with delayed jellyfish envenomation syndrome.

    PubMed

    Wang, Beilei; Zhang, Bo; Huo, Hua; Wang, Tao; Wang, Qianqian; Wu, Yuanlin; Xiao, Liang; Ren, Yuqi; Zhang, Liming

    2014-04-01

    Using the tentacle extract (TE) from the jellyfish Cyanea capillata, we have previously established a delayed jellyfish envenomation syndrome (DJES) model, which is meaningful for clinical interventions against jellyfish stings. However, the mechanism of DJES still remains unclear. Thus, this study aimed to explore its potential mechanism by detecting TE-induced microvasculature alterations in vivo and ex vivo. Using a third-generation synchrotron radiation facility, we, for the first time, directly observed the blood vessel alterations induced by jellyfish venom in vivo and ex vivo. Firstly, microvasculature imaging of whole-body mouse in vivo indicated that the small blood vessel branches in the liver and kidney in the TE-treated group, seemed much thinner than those in the control group. Secondly, 3D imaging of kidney ex vivo showed that the kidneys in the TE-treated group had incomplete vascular trees where distal vessel branches were partly missing and disorderly disturbed. Finally, histopathological analysis found that obvious morphological changes, especially hemorrhagic effects, were also present in the TE-treated kidney. Thus, TE-induced microvasculature changes might be one of the important mechanisms of multiple organ dysfunctions in DJES. In addition, the methods we employed here will probably facilitate further studies on developing effective intervention strategies against DJES.

  17. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

    PubMed Central

    Singh, Vijay K.; Wise, Stephen Y.; Fatanmi, Oluseyi O.; Beattie, Lindsay A.; Ducey, Elizabeth J.; Seed, Thomas M.

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. PMID:23814114

  18. In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

    NASA Technical Reports Server (NTRS)

    Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

    2003-01-01

    Understanding the radiation risks involved in spaceflight is of considerable importance, especially with the long-term occupation of ISS and the planned crewed exploration missions. Several independent causes may contribute to the overall risk to astronauts exposed to the complex space environment, such as exposure to GCR as well as SPES. Protons and high-Z energetic particles comprise the GCR spectrum and may exert considerable biological effects even at low fluence. There are also considerable uncertainties associated with secondary particle effects (e.g. HZE fragments, neutrons etc.). The interaction of protons and high-LET particles with biological materials at all levels of biological organization needs to be investigated fully in order to establish a scientific basis for risk assessment. The results of these types of investigation will foster the development of appropriately directed countermeasures. In this study, we compared the biological responses to proton irradiation presented to the target cells as a monoenergetic beam of particles of complex composition delivered to cells outside or inside a tissue phantom head placed in the United States EVA space suit helmet. Measurements of chromosome aberrations, apoptosis, and the induction of key proteins were made in bone marrow from CBA/CaJ and C57BL/6 mice at early and late times post exposure to radiation at 0, 0.5, 1 and 2 Gy while inside or outside of the helmet. The data showed that proton irradiation induced transmissible chromosomal/genomic instability in haematopoietic stem cells in both strains of mice under both irradiation conditions and especially at low doses. Although differences were noted between the mouse strains in the degree and kinetics of transforming growth factor-beta 1 and tumor necrosis factor-alpha secretion, there were no significant differences observed in the level of the induced instability under either radiation condition, or for both strains of mice. Consequently, when

  19. Administration of a Sigma Receptor Agonist Delays MCAO-Induced Neurodegeneration and White Matter Injury

    PubMed Central

    Leonardo, Christopher C.; Hall, Aaron A.; Collier, Lisa A.; Green, Suzanne M.; Willing, Alison E.; Pennypacker, Keith R.

    2010-01-01

    Many pharmacological treatments for stroke have afforded protection in rodent models but failed to show efficacy in clinical trials. This discrepancy may be due to the lack of long-term functional studies. Previously, delayed administration of the sigma receptor agonist 1,3-di-o-tolylguanidine (DTG) reduced infarct volume after middle cerebral artery occlusion (MCAO) in rats. The present study was conducted to determine whether the protective effects of DTG lead to improvements in behavioral functioning. Rats were subjected to MCAO and administered 7.5, 1.5, or 0.75 mg/kg DTG beginning 24 h post-surgery. Histological outcomes (96 h, 2 weeks, and 5 weeks) were compared with performance on a series of behavioral tests (2 and 4 weeks). Fluoro-Jade staining and immunohistochemistry were used to assess infarct volume and immune cell recruitment. All doses significantly reduced infarct volume and perturbation of striatal white matter tracts at 96 h. These reductions were associated with decreased numbers of CD11b-positive amoeboid microglia/macrophages. Despite short-term efficacy, DTG failed to improve behavioral outcomes or reduce infarct volumes after 96 h. While DTG may prove beneficial as a short-term therapy, these data highlight the importance of long-term functional recovery when evaluating novel therapies to treat stroke. PMID:20563232

  20. Good outcome after delayed surgery for orbitocranial non-missile penetrating brain injury

    PubMed Central

    Caporlingua, Alessandro; Caporlingua, Federico; Lenzi, Jacopo

    2016-01-01

    Nonmissile orbitocranial penetrating brain injuries are uncommonly dealt with in a civilian context. Surgical management is controversial, due to the lack of widely accepted guidelines. A 52-year-old man was hit in his left eye by a metallic foreign body (FB). Head computed tomography (CT) scan showed a left subcortical parietal FB with a considerable hemorrhagic trail originating from the left orbital roof. Surgical treatment was staged; an exenteratio oculi and a left parietal craniotomy to extract the FB under intraoperative CT guidance were performed at post trauma day third and sixth, respectively. A postoperative infectious complication was treated conservatively. The patient retained a right hemiparesis (3/5) and was transferred to rehabilitation in good clinical conditions at day 49th. He had suspended antiepilectic therapy at that time. A case-by-case tailored approach is mandatory to achieve the best outcome in such a heterogeneous nosological entity. Case reporting is crucial to further understand its mechanism and dynamics. PMID:27366265

  1. Assessment of Cell-Cycle Arrest Biomarkers to Predict Early and Delayed Acute Kidney Injury

    PubMed Central

    Bell, Max; Larsson, Anders; Venge, Per; Bellomo, Rinaldo; Mårtensson, Johan

    2015-01-01

    Purpose. To assess urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein 7 ([TIMP-2]·[IGFBP7]), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney injury predictors (AKI) exploring the association of nonrenal factors with elevated biomarker levels. Methods. We studied 94 patients with urine collected within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Predictive performance was assessed by the area under the receiver operating characteristics (ROC) curve. Associations between biomarkers and clinical factors were assessed by multivariate linear regression. Results. Overall, 19 patients (20%) developed AKI within 48 hours. [TIMP-2]·[IGFBP7], NGAL, or cystatin-C admission levels did not differ between patients without AKI and patients developing AKI. [TIMP-2]·[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34–0.51). Diabetes was independently associated with higher [TIMP-2]·[IGFBP7] levels (P = 0.02) but AKI was not (P = 0.24). Sepsis was independently associated with higher NGAL (P < 0.001) and cystatin-C (P = 0.003) levels. Conclusions. Urinary [TIMP-2]·[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in general ICU patients since urine levels of these biomarkers are affected by factors other than AKI and their performance can be poor. PMID:25866432

  2. Development and Characterization of a High Throughput Screen to investigate the delayed Effects of Radiations Commonly Encountered in Space

    NASA Astrophysics Data System (ADS)

    Morgan, W. F.

    Astronauts based on the space station or on long-term space missions will be exposed to high Z radiations in the cosmic environment In order to evaluate the potentially deleterious effects of exposure to radiations commonly encountered in space we have developed and characterized a high throughput assay to detect mutation deletion events and or hyperrecombination in the progeny of exposed cells This assay is based on a plasmid vector containing a green fluorescence protein reporter construct We have shown that after stable transfection of the vector into human or hamster cells this construct can identify mutations specifically base changes and deletions as well as recombination events e g gene conversion or homologous recombination occurring as a result of exposure to ionizing radiation Our focus has been on those events occurring in the progeny of an irradiated cell that are potentially associated with radiation induced genomic instability rather than the more conventional assays that evaluate the direct immediate effects of radiation exposure Considerable time has been spent automating analysis of surviving colonies as a function of time after irradiation in order to determine when delayed instability is induced and the consequences of this delayed instability The assay is now automated permitting the evaluation of potentially rare events associated with low dose low dose rate radiations commonly encountered in space

  3. Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats.

    PubMed

    Liu, Shiyao; Yang, Yanwei; Jin, Mu; Hou, Siyu; Dong, Xiuhua; Lu, Jiakai; Cheng, Weiping

    2016-09-15

    Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling

  4. Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats.

    PubMed

    Liu, Shiyao; Yang, Yanwei; Jin, Mu; Hou, Siyu; Dong, Xiuhua; Lu, Jiakai; Cheng, Weiping

    2016-09-15

    Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling

  5. Variable ultrasound trigger delay for improved magnetic resonance acoustic radiation force imaging

    NASA Astrophysics Data System (ADS)

    Mougenot, Charles; Waspe, Adam; Looi, Thomas; Drake, James M.

    2016-01-01

    Magnetic resonance acoustic radiation force imaging (MR-ARFI) allows the quantification of microscopic displacements induced by ultrasound pulses, which are proportional to the local acoustic intensity. This study describes a new method to acquire MR-ARFI maps, which reduces the measurement noise in the quantification of displacement as well as improving its robustness in the presence of motion. Two MR-ARFI sequences were compared in this study. The first sequence ‘variable MSG’ involves switching the polarity of the motion sensitive gradient (MSG) between odd and even image frames. The second sequence named ‘static MSG’ involves a variable ultrasound trigger delay to sonicate during the first or second MSG for odd and even image frames, respectively. As previously published, the data acquired with a variable MSG required the use of reference data acquired prior to any sonication to process displacement maps. In contrary, data acquired with a static MSG were converted to displacement maps without using reference data acquired prior to the sonication. Displacement maps acquired with both sequences were compared by performing sonications for three different conditions: in a polyacrylamide phantom, in the leg muscle of a freely breathing pig and in the leg muscle of pig under apnea. The comparison of images acquired at even image frames and odd image frames indicates that the sequence with a static MSG provides a significantly better steady state (p  <  0.001 based on a Student’s t-test) than the images acquired with a variable MSG. In addition no reference data prior to sonication were required to process displacement maps for data acquired with a static MSG. The absence of reference data prior to sonication provided a 41% reduction of the spatial distribution of noise (p  <  0.001 based on a Student’s t-test) and reduced the sensitivity to motion for displacements acquired with a static MSG. No significant differences were expected and

  6. Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

    SciTech Connect

    Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won; Oh, Sang Ho; Lee, Yun-Sil; Lee, Eun-Jung; Cho, Jaeho

    2015-05-08

    Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.

  7. Ramipril-induced delayed myocardial protection against free radical injury involves bradykinin B2 receptor-NO pathway and protein synthesis

    PubMed Central

    Jin, Zhu-Qiu; Chen, Xiu

    1998-01-01

    The aim of the present study was to examine whether ramipril induces delayed myocardial protection against free radical injuries ex vivo and to determine the possible role of the bradykinin B2–nitric oxide (NO) pathway, prostaglandins(PGs) and protein synthesis in this delayed adaptive response.Rats were pretreated with ramipril (10 or 50 μg kg−1, i.v.) and hearts were isolated after 24, 48 and 72 h. Langendorff hearts were subjected to 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical-induced injury.Left ventricular developed pressure (LVDP) and its maximal increase velocity (+dP/dtmax), coronary flow (CF), heart rate (HR), lactate dehydrogenase (LDH) in coronary effluent and thiobarbituric acid reactive substances (TBARS) in the myocardium were measured.The results showed that in the DPPH control group, 20 min after free radical-induced injury, LVDP, +dP/dtmax, CF, HR declined, whereas TBARS and LDH increased significantly. The above cardiac function parameters were significantly improved in RAM-pretreated rats after 24 and 48 h.Pretreatment with HOE 140, the selective bradykinin B2 receptor antagonist, NG-nitro-L-arginine, the NO synthase inhibitor, and actinomycin D, the RNA transcription inhibitor, prior to ramipril injection abolished the beneficial effects of ramipril at 24 h while indomethacin, a cyclooxygenase inhibitor, pretreatment had no effect on ramipril-induced delayed protection.In conclusion, ramipril induces delayed myocardial protection against free radical injury in the rat heart. This delayed protection was sustained for 48 h, is associated with the bradykinin B2 receptor–NO pathway and depends on protein but not prostaglandin synthesis. PMID:9806340

  8. Comparison of the protective action of glutathione and cysteamine on radiation-induced mitotic delay in cultured S-5 cells.

    PubMed

    Kawasaki, S; Kobayashi, M; Hashimoto, H; Nakanishi, T

    1979-06-01

    The protective effect of glutathione (GSH) and cysteamine (MEA) on radiation-induced mitotic delay in cultured mammalian L-5 cells was studied. Cells treated with 20 mM of GSH during irradiation with 2 Gy (200 rad) showed faster recovery of the mitotic index than control cells irradiated without chemical treatment; however, GSH had no effect on mitotic delay time. Inhibition of mitosis was observed with 80, 100, and 120 mM of GSH. Cells treated with 5 mM of MEA during irradiation also showed faster recovery of the mitotic index than the controls, but in addition the delay time was shortened. Progression of G2-phase cells treated with 5-fluorouracil to mitosis after irradiation was protected by MEA but not by GSH. Progression of S-phase cells labeled with 3H-thymidine to mitosis was accelerated by both agents during irradiation.

  9. Moderate elevations in international normalized ratio should not lead to delays in neurosurgical intervention in patients with traumatic brain injury

    PubMed Central

    Rowell, Susan E.; Barbosa, Ronald R.; Lennox, Tori C.; Fair, Kelly A.; Rao, Abigail J.; Underwood, Samantha J.; Schreiber, Martin A.

    2015-01-01

    BACKGROUND The management of severe traumatic brain injury (TBI) frequently involves invasive intracranial monitoring or cranial surgery. In our institution, intracranial procedures are often deferred until an international normalized ratio (INR) of less than 1.4 is achieved. There is no evidence that a moderately elevated INR is associated with increased risk of bleeding in patients undergoing neurosurgical intervention (NI). Thrombelastography (TEG) provides a functional assessment of clotting and has been shown to better predict clinically relevant coagulopathy compared with INR. We hypothesized that in patients with TBI, an elevated INR would result in increased time to NI and would not be associated with coagulation abnormalities based on TEG. METHODS A secondary analysis of prospectively collected data was performed in trauma patients with intracranial hemorrhage that underwent NI (defined as cranial surgery or intracranial pressure monitoring) within 24 hours of arrival. Time from admission to NI was recorded. TEG and routine coagulation assays were obtained at admission. Patients were considered hypocoagulable based on INR if their admission INR was greater than 1.4 (high INR). Manufacturer-specified values were used to determine hypocoagulability for each TEG variable. RESULTS Sixty-one patients (median head Abbreviated Injury Scale [AIS] score, 5) met entry criteria, of whom 16% had high INR. Demographic, physiologic, and injury scoring data were similar between groups. The median time to NI was longer in patients with high INR (358 minutes vs. 184 minutes, p = 0.027). High-INR patients were transfused more plasma than patients with an INR of 1.4 or less (2 U vs. 0 U, p = 0.01). There was no association between an elevated INR and hypocoagulability based on TEG. CONCLUSION TBI patients with an admission INR of greater than 1.4 had a longer time to NI. The use of plasma transfusion to decrease the INR may have contributed to this delay. A moderately

  10. Optically-switched submillimeter-wave oscillator and radiator having a switch-to-switch propagation delay

    NASA Technical Reports Server (NTRS)

    Spencer, Michael G. (Inventor); Maserjian, Joseph (Inventor)

    1995-01-01

    A submillimeter wave-generating integrated circuit includes an array of N photoconductive switches biased across a common voltage source and an optical path difference from a common optical pulse of repetition rate f sub 0 providing a different optical delay to each of the switches. In one embodiment, each incoming pulse is applied to successive ones of the N switches with successive delays. The N switches are spaced apart with a suitable switch-to-switch spacing so as to generate at the output load or antenna radiation of a submillimeter wave frequency f on the order of N f sub 0. Preferably, the optical pulse has a repetition rate of at least 10 GHz and N is of the order of 100, so that the circuit generates radiation of frequency of the order of or greater than 1 Terahertz.

  11. Mesenchymal stem cells stimulate intestinal stem cells to repair radiation-induced intestinal injury

    PubMed Central

    Gong, Wei; Guo, Mengzheng; Han, Zhibo; Wang, Yan; Yang, Ping; Xu, Chang; Wang, Qin; Du, Liqing; Li, Qian; Zhao, Hui; Fan, Feiyue; Liu, Qiang

    2016-01-01

    The loss of stem cells residing in the base of the intestinal crypt has a key role in radiation-induced intestinal injury. In particular, Lgr5+ intestinal stem cells (ISCs) are indispensable for intestinal regeneration following exposure to radiation. Mesenchymal stem cells (MSCs) have previously been shown to improve intestinal epithelial repair in a mouse model of radiation injury, and, therefore, it was hypothesized that this protective effect is related to Lgr5+ ISCs. In this study, it was found that, following exposure to radiation, transplantation of MSCs improved the survival of the mice, ameliorated intestinal injury and increased the number of regenerating crypts. Furthermore, there was a significant increase in Lgr5+ ISCs and their daughter cells, including Ki67+ transient amplifying cells, Vil1+ enterocytes and lysozyme+ Paneth cells, in response to treatment with MSCs. Crypts isolated from mice treated with MSCs formed a higher number of and larger enteroids than those from the PBS group. MSC transplantation also reduced the number of apoptotic cells within the small intestine at 6 h post-radiation. Interestingly, Wnt3a and active β-catenin protein levels were increased in the small intestines of MSC-treated mice. In addition, intravenous delivery of recombinant mouse Wnt3a after radiation reduced damage in the small intestine and was radioprotective, although not to the same degree as MSC treatment. Our results show that MSCs support the growth of endogenous Lgr5+ ISCs, thus promoting repair of the small intestine following exposure to radiation. The molecular mechanism of action mediating this was found to be related to increased activation of the Wnt/β-catenin signaling pathway. PMID:27685631

  12. Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation. Final report

    SciTech Connect

    Baulch, Janet

    2013-09-11

    This is a 'glue grant' that was part of a DOE Low Dose project entitled 'Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation'. This collaborative program has involved Drs. David L. Springer from Pacific Northwest National Laboratory (PNNL), John H. Miller from Washington State University, Tri-cities (WSU) and William F. Morgan then from the University of Maryland, Baltimore (UMB). In July 2008, Dr. Morgan moved to PNNL and Dr. Janet E. Baulch became PI for this project at University of Maryland. In November of 2008, a one year extension with no new funds was requested to complete the proteomic analyses. The project stemmed from studies in the Morgan laboratory demonstrating that genomically unstable cells secret a soluble factor or factors into the culture medium, that cause cytogenetic aberrations and apoptosis in normal parental GM10115 cells. The purpose of this project was to identify the death inducing effect (DIE) factor or factors, estimate their relative abundance, identify the cell signaling pathways involved and finally recapitulate DIE in normal cells by exogenous manipulation of putative DIE factors in culture medium. As reported in detail in the previous progress report, analysis of culture medium from the parental cell line, and stable and unstable clones demonstrated inconsistent proteomic profiles as relate to candidate DIE factors. While the proposed proteomic analyses did not provide information that would allow DIE factors to be identified, the analyses provided another important set of observations. Proteomic analysis suggested that proteins associated with the cellular response to oxidative stress and mitochondrial function were elevated in the medium from unstable clones in a manner consistent with mitochondrial dysfunction. These findings correlate with previous studies of these clones that demonstrated functional differences between the mitochondria of stable and unstable clones. These

  13. Delayed voluntary exercise does not enhance cognitive performance after hippocampal injury: an investigation of differentially distributed exercise protocols

    PubMed Central

    Wogensen, Elise; Gram, Marie Gajhede; Sommer, Jens Bak; Vilsen, Christina Rytter; Mogensen, Jesper; Malá, Hana

    2016-01-01

    Voluntary exercise has previously been shown to enhance cognitive recovery after acquired brain injury (ABI). The present study evaluated effects of two differentially distributed protocols of delayed, voluntary exercise on cognitive recovery using an allocentric place learning task in an 8-arm radial maze. Fifty-four Wistar rats were subjected to either bilateral transection of the fimbria-fornix (FF) or to sham surgery. Twenty-one days postinjury, the animals started exercising in running wheels either for 14 consecutive days (FF/exercise daily [ExD], sham/ExD) or every other day for 14 days (FF/exercise every second day [ExS], sham/ExS). Additional groups were given no exercise treatment (FF/not exercise [NE], sham/NE). Regardless of how exercise was distributed, we found no cognitively enhancing effects of exercise in the brain injured animals. Design and protocol factors possibly affecting the efficacy of post-ABI exercise are discussed. PMID:27807517

  14. Pulmonary Injury after Combined Exposures to Low-Dose Low-LET Radiation and Fungal Spores

    PubMed Central

    Marples, B.; Downing, L.; Sawarynski, K. E.; Finkelstein, J. N.; Williams, J. P.; Martinez, A. A.; Wilson, G. D.; Sims, M. D.

    2013-01-01

    Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury. PMID:21275606

  15. High-Precision Time Delay Control with Continuous Phase Shifter for Pump-Probe Experiments Using Synchrotron Radiation Pulses

    SciTech Connect

    Tanaka, Yoshihito; Ohshima, Takashi; Moritomo, Yutaka; Tanaka, Hitoshi; Takata, Masaki

    2010-06-23

    Brilliant pulsed x-ray synchrotron radiation (SR) is useful for pump-probe experiment such as time-resolved x-ray diffraction, x-ray absorption fine structure, and x-ray spectroscopy. For laser pump-SR x-ray probe experiments, short pulsed lasers are generally synchronized to the SR master oscillator controlling the voltage for acceleration of electron bunches in an accelerator, and the interval between the laser and the SR pulses is changed around the time scale of target phenomenon. Ideal delay control produces any time delay as keeping the time-precision and pointing-stability of optical pulses at a sample position. We constructed the time delay control module using a continuous phase shifter of radio frequency signal and a frequency divider, which can produce the delayed trigger pulses to the laser without degradation of the time precision and the pointing stability. A picoseconds time-resolved x-ray diffraction experiment was demonstrated at SPring-8 storage ring for fast lattice response by femtosecond pulsed laser irradiation, and suggested the possibility of accurate sound velocity measurement. A delay control unit operating with subpicosecond precision has also been designed for femtosecond pump-probe experiments using a free electron laser at SPring-8 campus.

  16. Role of GADD45a in murine models of radiation- and bleomycin-induced lung injury.

    PubMed

    Mathew, Biji; Takekoshi, Daisuke; Sammani, Saad; Epshtein, Yulia; Sharma, Rajesh; Smith, Brett D; Mitra, Sumegha; Desai, Ankit A; Weichselbaum, Ralph R; Garcia, Joe G N; Jacobson, Jeffrey R

    2015-12-15

    We previously reported protective effects of GADD45a (growth arrest and DNA damage-inducible gene 45 alpha) in murine ventilator-induced lung injury (VILI) via effects on Akt-mediated endothelial cell signaling. In the present study we investigated the role of GADD45a in separate murine models of radiation- and bleomycin-induced lung injury. Initial studies of wild-type mice subjected to single-dose thoracic radiation (10 Gy) confirmed a significant increase in lung GADD45a expression within 24 h and persistent at 6 wk. Mice deficient in GADD45a (GADD45a(-/-)) demonstrated increased susceptibility to radiation-induced lung injury (RILI, 10 Gy) evidenced by increased bronchoalveolar lavage (BAL) fluid total cell counts, protein and albumin levels, and levels of inflammatory cytokines compared with RILI-challenged wild-type animals at 2 and 4 wk. Furthermore, GADD45a(-/-) mice had decreased total and phosphorylated lung Akt levels both at baseline and 6 wk after RILI challenge relative to wild-type mice while increased RILI susceptibility was observed in both Akt(+/-) mice and mice treated with an Akt inhibitor beginning 1 wk prior to irradiation. Additionally, overexpression of a constitutively active Akt1 transgene reversed RILI-susceptibility in GADD45a(-/-) mice. In separate studies, lung fibrotic changes 2 wk after treatment with bleomycin (0.25 U/kg IT) was significantly increased in GADD45a(-/-) mice compared with wild-type mice assessed by lung collagen content and histology. These data implicate GADD45a as an important modulator of lung inflammatory responses across different injury models and highlight GADD45a-mediated signaling as a novel target in inflammatory lung injury clinically.

  17. Pine polyphenols from Pinus koraiensis prevent injuries induced by gamma radiation in mice

    PubMed Central

    Li, Hui; Xu, Yier; Sun, Guicai

    2016-01-01

    Pine polyphenols (PPs) are bioactive dietary constituents that enhance health and help prevent diseases through antioxidants. Antioxidants reduce the level of oxidative damages caused by ionizing radiation (IR). The main purpose of this paper is to study the protective effect of PPs on peripheral blood, liver and spleen injuries in mice induced by IR. ICR (Institute of Cancer Research) male mice were administered orally with PPs (200 mg/kg b.wt.) once daily for 14 consecutive days prior to 7 Gy γ-radiations. PPs showed strong antioxidant activities. PPs significantly increased white blood cells, red blood cells and platelets counts. PPs also significantly reduced lipid peroxidation and increased the activities of superoxide dismutase, catalase and glutathione peroxidases, and the level of glutathione. PPs reduced the spleen morphologic injury. In addition, PPs inhibited mitochondria-dependent apoptosis pathways in splenocytes induced by IR. These results indicate that PPs are radioprotective promising reagents. PMID:27069807

  18. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway.

    PubMed

    Liu, Yunen; Tan, Dehong; Tong, Changci; Zhang, Yubiao; Xu, Ying; Liu, Xinwei; Gao, Yan; Hou, Mingxiao

    2015-12-01

    The purpose of this study was to explore the effect of blueberry anthocyanins (BA) on radiation-induced lung injury and investigate the mechanism of action. Seven days after BA(20 and 80 mg/kg/d)administration, 6 weeks old male Sprague-Dawley rats rats were irradiated by LEKTA precise linear accelerator at a single dose of 20 Gy only once. and the rats were continuously treated with BA for 4 weeks. Moreover, human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with either control-siRNA or siRNA targeting protein kinase R (PKR). Cells were then irradiated and treated with 75 μg/mL BA for 72 h. The results showed that BA significantly ameliorated radiation-induced lung inflammation, lung collagen deposition, apoptosis and PKR expression and activation. In vitro, BA significantly protected cells from radiation-induced cell death through modulating expression of Bcl-2, Bax and Caspase-3. Suppression of PKR by siRNA resulted in ablation of BA protection on radiation-induced cell death and modulation of anti-apoptotic and pro-apoptotic proteins, as well as Caspase-3 expression. These findings suggest that BA is effective in ameliorating radiation-induced lung injury, likely through the PKR signaling pathway. PMID:26551926

  19. An immunohistochemical panel to assess ultraviolet radiation-associated oxidative skin injury.

    PubMed

    Mamalis, Andrew; Fiadorchanka, Natallia; Adams, Lauren; Serravallo, Melissa; Heilman, Edward; Siegel, Daniel; Brody, Neil; Jagdeo, Jared

    2014-05-01

    Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years (DALYs), and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation.

  20. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway.

    PubMed

    Liu, Yunen; Tan, Dehong; Tong, Changci; Zhang, Yubiao; Xu, Ying; Liu, Xinwei; Gao, Yan; Hou, Mingxiao

    2015-12-01

    The purpose of this study was to explore the effect of blueberry anthocyanins (BA) on radiation-induced lung injury and investigate the mechanism of action. Seven days after BA(20 and 80 mg/kg/d)administration, 6 weeks old male Sprague-Dawley rats rats were irradiated by LEKTA precise linear accelerator at a single dose of 20 Gy only once. and the rats were continuously treated with BA for 4 weeks. Moreover, human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with either control-siRNA or siRNA targeting protein kinase R (PKR). Cells were then irradiated and treated with 75 μg/mL BA for 72 h. The results showed that BA significantly ameliorated radiation-induced lung inflammation, lung collagen deposition, apoptosis and PKR expression and activation. In vitro, BA significantly protected cells from radiation-induced cell death through modulating expression of Bcl-2, Bax and Caspase-3. Suppression of PKR by siRNA resulted in ablation of BA protection on radiation-induced cell death and modulation of anti-apoptotic and pro-apoptotic proteins, as well as Caspase-3 expression. These findings suggest that BA is effective in ameliorating radiation-induced lung injury, likely through the PKR signaling pathway.

  1. An Immunohistochemical Panel to Assess Ultraviolet Radiation Associated Oxidative Skin Injury

    PubMed Central

    Adams, L; Serravallo, M; Heilman, E; Siegel, D; Brody, N; Jagdeo, J

    2015-01-01

    Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years, and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation. PMID:24809881

  2. An immunohistochemical panel to assess ultraviolet radiation-associated oxidative skin injury.

    PubMed

    Mamalis, Andrew; Fiadorchanka, Natallia; Adams, Lauren; Serravallo, Melissa; Heilman, Edward; Siegel, Daniel; Brody, Neil; Jagdeo, Jared

    2014-05-01

    Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years (DALYs), and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation. PMID:24809881

  3. Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

    PubMed Central

    Balentova, Sona; Adamkov, Marian

    2015-01-01

    Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

  4. Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats

    PubMed Central

    Kim, Jin Hyun; Kim, Kyung Mi; Jung, Myeong Hee; Jung, Jung Hwa; Kang, Ki Mun; Jeong, Bae Kwon; Kim, Jin Pyeong; Park, Jung Je; Woo, Seung Hoon

    2016-01-01

    Purpose Radiation therapy is a treatment for patients with head and neck (HN) cancer. However, radiation exposure to the HN often induces salivary gland (SG) dysfunction. We investigated the effect of α-lipoic acid (ALA) on radiation-induced SG injury in rats. Results ALA preserved acinoductal integrity and acinar cell secretary function following irradiation. These results are related to the mechanisms by which ALA inhibits oxidative stress by inhibiting gp91 mRNA and 8-OHdG expression and apoptosis of acinar cells and ductal cells by inactivating MAPKs in the early period and expression of inflammation-related factors including NF-κB, IκB-α, and TGF-β1 and fibrosis in late irradiated SG. ALA effects began in the acute phase and persisted for at least 56 days after irradiation. Materials and Methods Rats were assigned to followings: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation. The neck area including the SG was evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were killed at 4, 7, 28, and 56 days after radiation. Conclusions Our results show that ALA could be used to ameliorate radiation-induced SG injury in patients with HN cancer. PMID:27072584

  5. Central Nervous System Injury – A Newly Observed Bystander Effect of Radiation

    PubMed Central

    Feiock, Caitlin; Yagi, Masashi; Maidman, Adam; Rendahl, Aaron; Hui, Susanta; Seelig, Davis

    2016-01-01

    The unintended side effects of cancer treatment are increasing recognized. Among these is a syndrome of long-term neurocognitive dysfunction called cancer/chemotherapy related cognitive impairment. To date, all studies examining the cognitive impact of cancer treatment have emphasized chemotherapy. Radiation-induced bystander effects have been described in cell culture and, to a limited extent, in rodent model systems. The purpose of this study was to examine, for the first time, the impact of non-brain directed radiation therapy on the brain in order to elucidate its potential relationship with cancer/chemotherapy related cognitive impairment. To address this objective, female BALB/c mice received either a single 16 gray fraction of ionizing radiation to the right hind limb or three doses of methotrexate, once per week for three consecutive weeks. Mice were sacrificed either 3 or 30 days post-treatment and brain injury was determined via quantification of activated astrocytes and microglia. To characterize the effects of non-brain directed radiation on brain glucose metabolism, mice were evaluated by fluorodeoxygluocose positron emission tomography. A single fraction of 16 gray radiation resulted in global decreases in brain glucose metabolism, a significant increase in the number of activated astrocytes and microglia, and increased TNF-α expression, all of which lasted up to 30 days post-treatment. This inflammatory response following radiation therapy was statistically indistinguishable from the neuroinflammation observed following methotrexate administration. In conclusion, non-brain directed radiation was sufficient to cause significant brain bystander injury as reflected by multifocal hypometabolism and persistent neuroinflammation. These findings suggest that radiation induces significant brain bystander effects distant from the irradiated cells and tissues. These effects may contribute to the development of cognitive dysfunction in treated human cancer

  6. Gating delays for two respiratory motion sensors in scanned particle radiation therapy

    NASA Astrophysics Data System (ADS)

    Steidl, P.; Haberer, T.; Durante, M.; Bert, C.

    2013-11-01

    Gating is one option for radiotherapy of tumours that move intrafractionally due to respiration. Delays of the motion monitoring system can lead to a shift of the gating window and thus slightly shifted dose distributions. We studied the delay of two motion monitoring systems which use the motion of the chest wall as surrogate for tumour motion. Delays and their dosimetric influence were determined against a precise motion acquisition system in a phantom study. The measurement data were supplemented by dedicated simulations of the experimental setup. Finally, the dosimetric influence for patient treatments was estimated for a lung tumour case using the extreme situation of a radiosurgery setting with a single field. We determined delays of 132 ± 18 ms and 103 ± 22 ms for the two systems. There was no significant difference between beam start and beam stop delay. Even for delays of 200 ms the dosimetric influence in a single-field radiosurgery setting is moderate (V95 = 96.5%, V107 = 8.5%, D5-D95 = 13%). We conclude, that the delay of the motion monitoring system should be part of the commissioning process for gated treatments. The dosimetric impact should be studied in detail prior treatments with a scanned ion beam.

  7. Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma.

    PubMed

    Gordon, Ira K; Lu, Jie; Graves, Christian A; Huntoon, Kristin; Frerich, Jason M; Hanson, Ryan H; Wang, Xiaoping; Hong, Christopher S; Ho, Winson; Feldman, Michael J; Ikejiri, Barbara; Bisht, Kheem; Chen, Xiaoyuan S; Tandle, Anita; Yang, Chunzhang; Arscott, W Tristram; Ye, Donald; Heiss, John D; Lonser, Russell R; Camphausen, Kevin; Zhuang, Zhengping

    2015-07-01

    Protein phosphatase 2A (PP2A) is a tumor suppressor whose function is lost in many cancers. An emerging, though counterintuitive, therapeutic approach is inhibition of PP2A to drive damaged cells through the cell cycle, sensitizing them to radiotherapy. We investigated the effects of PP2A inhibition on U251 glioblastoma cells following radiation treatment in vitro and in a xenograft mouse model in vivo. Radiotherapy alone augmented PP2A activity, though this was significantly attenuated with combination LB100 treatment. LB100 treatment yielded a radiation dose enhancement factor of 1.45 and increased the rate of postradiation mitotic catastrophe at 72 and 96 hours. Glioblastoma cells treated with combination LB100 and radiotherapy maintained increased γ-H2AX expression at 24 hours, diminishing cellular repair of radiation-induced DNA double-strand breaks. Combination therapy significantly enhanced tumor growth delay and mouse survival and decreased p53 expression 3.68-fold, compared with radiotherapy alone. LB100 treatment effectively inhibited PP2A activity and enhanced U251 glioblastoma radiosensitivity in vitro and in vivo. Combination treatment with LB100 and radiation significantly delayed tumor growth, prolonging survival. The mechanism of radiosensitization appears to be related to increased mitotic catastrophe, decreased capacity for repair of DNA double-strand breaks, and diminished p53 DNA-damage response pathway activity.

  8. Protection of normal tissue against late radiation injury by WR-2721. [/sup 60/Co; rats

    SciTech Connect

    Utley, J.F.; Quinn, C.A.; White, F.C.; Seaver, N.A.; Bloor, C.M.

    1981-02-01

    The ability of WR-2721 to protect against late radiation damage has been studied in skin, muscle, and vascular tissues of rats. Animals treated with and without WR-2721 received irradiation to the left hind limb; representative groups were killed at intervals ranging from 72 h to 6 months. Comparison of all drug-treated and non-drug-treated animals showed significant protection (P = less than or equal to 0.05). The time pattern of injury in non-drug-treated rats was biphasic, with significant damage occurring at 72 h and 1 week, returning to normal between 1 and 3 months, but showing significant late damage at 6 months (P = less than or equal to 0.001). Again, this injury pattern did not appear in WR-2721-treated rats. Thus the ability of WR-2721 to protect against acute and chronic radiation injury in vessels, skin, and muscle indicates that an increased therapeutic gain can be expected when this drug is used in clinical radiation therapy.

  9. Delayed Cerebral Radiation Necrosis after Neutron Beam Radiation of a Parotid Adenocarcinoma: A Case Report and Review of the Literature

    PubMed Central

    Hong, Christopher S.; Gokozan, Hamza N.; Otero, José J.; Guiou, Michael; Elder, J. Bradley

    2014-01-01

    Cerebral radiation necrosis (CRN) is a well described possible complication of radiation for treatment of intracranial pathology. However, CRN as sequelae of radiation to extracranial sites is rare. Neutron beam radiation is a highly potent form of radiotherapy that may be used to treat malignant tumors of the salivary glands. This report describes a patient who underwent neutron beam radiation for a parotid adenocarcinoma and who developed biopsy-confirmed temporal lobe radiation necrosis thirty months later. This represents the longest time interval described to date, from initial neutron radiation for extracranial pathology to development of CRN. Two other detailed case studies exist in the literature and are described in this report. These reports as well as our patient's case are reviewed, and additional recommendations are made to minimize the development of CRN after extracranial neutron beam radiation. Physicians should include the possible diagnosis of CRN in any patient with new neurologic signs or symptoms and a history of head and neck radiation that included planned fields extending to the base of the skull. Counseling of patients prior to neutron beam radiation should include potential neurologic complications associated with CRN and risks of treatment for CRN including neurosurgical intervention. PMID:25349750

  10. Delayed cerebral radiation necrosis after neutron beam radiation of a parotid adenocarcinoma: a case report and review of the literature.

    PubMed

    Hong, Christopher S; Gokozan, Hamza N; Otero, José J; Guiou, Michael; Elder, J Bradley

    2014-01-01

    Cerebral radiation necrosis (CRN) is a well described possible complication of radiation for treatment of intracranial pathology. However, CRN as sequelae of radiation to extracranial sites is rare. Neutron beam radiation is a highly potent form of radiotherapy that may be used to treat malignant tumors of the salivary glands. This report describes a patient who underwent neutron beam radiation for a parotid adenocarcinoma and who developed biopsy-confirmed temporal lobe radiation necrosis thirty months later. This represents the longest time interval described to date, from initial neutron radiation for extracranial pathology to development of CRN. Two other detailed case studies exist in the literature and are described in this report. These reports as well as our patient's case are reviewed, and additional recommendations are made to minimize the development of CRN after extracranial neutron beam radiation. Physicians should include the possible diagnosis of CRN in any patient with new neurologic signs or symptoms and a history of head and neck radiation that included planned fields extending to the base of the skull. Counseling of patients prior to neutron beam radiation should include potential neurologic complications associated with CRN and risks of treatment for CRN including neurosurgical intervention. PMID:25349750

  11. STUDIES IN WORKMEN'S COMPENSATION AND RADIATION INJURY. VOLUME III, A REPORT ON IONIZING RADIATION RECORD KEEPING.

    ERIC Educational Resources Information Center

    Atomic Energy Commission, Washington, DC.

    THE SUCCESSFUL OPERATION OF THE PERMISSIBLE LEVEL CONCEPT OF RADIATION CONTROL NECESSARILY ENTAILS A COMPREHENSIVE SYSTEM UNDER WHICH EXPOSURE MUST BE RECORDED AND EMPLOYEES NOTIFIED OF THEIR EXPOSURE HISTORY. IN AN INVESTIGATION OF RECORD KEEPING NECESSARY TO PROCESS RADIATION CLAIMS, QUESTIONNAIRES OR LETTERS WERE RECEIVED FROM 45 STATE AGENCIES…

  12. Injury response checkpoint and developmental timing in insects

    PubMed Central

    Hackney, Jennifer F; Cherbas, Peter

    2014-01-01

    In insects, localized tissue injury often leads to global (organism-wide) delays in development and retarded metamorphosis. In Drosophila, for example, injuries to the larval imaginal discs can retard pupariation and prolong metamorphosis. Injuries induced by treatments such as radiation, mechanical damage and induction of localized cell death can trigger similar delays. In most cases, the duration of the developmental delay appears to be correlated with the extent of damage, but the effect is also sensitive to the developmental stage of the treated animal. The proximate cause of the delays is likely a disruption of the ecdysone signaling pathway, but the intermediate steps leading from tissue injury and/or regeneration to that disruption remain unknown. Here, we review the evidence for injury-induced developmental delays, and for a checkpoint or checkpoints associated with the temporal progression of development and the on-going efforts to define the mechanisms involved. PMID:25833067

  13. Combination of chondroitinase ABC, glial cell line-derived neurotrophic factor and Nogo A antibody delayed-release microspheres promotes the functional recovery of spinal cord injury.

    PubMed

    Zhang, Yu; Gu, Zuchao; Qiu, Guixing; Song, Yueming

    2013-11-01

    Spinal cord injury (SCI) is one of the most devastating injuries for patients. Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophic factor for the regeneration of the spinal neuraxial bundle, but GDNF would degrade rapidly if the protein was injected into the site of injury; thus, it cannot exert its fullest effects. Therefore, we introduced a delivery system of GDNF, poly(lactide-co-glycolic acid) (PLGA) delayed-release microspheres, in the current study and observed the effect of PLGA-GDNF and the combination of PLGA-GDNF and another 2 agents PLGA-chondroitinase ABC (ChABC) and PLGA-Nogo A antibody in the treatment of SCI rats. Our results showed that PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres could elevate the locomotor scores of SCI rats. The effect of PLGA-GDNF was much better than that of GDNF. The cortical somatosensory evoked potential was also improved by PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres. Our results suggest that PLGA delayed-release microsphere may be a useful and effective tool in delivering protein agents into the injury sites of patients with SCI. This novel combination therapy may provide a new idea in promoting the functional recovery of the damaged spinal cord.

  14. Radiation Injury Treatment Network®: Preparedness Through a Coalition of Cancer Centers.

    PubMed

    Case, Cullen

    2016-08-01

    This article provides an overview of Radiation Injury Treatment Network® (RITN), its preparedness activities and capabilities, including training and educating over 11,500 hospital staff, coordinating over 500 exercises, developing treatment guidelines, developing standard operating procedures, and being recognized by the U.S. federal government as a national response asset. The RITN provides comprehensive evaluation and treatment for victims with marrow toxic injuries. Many of the casualties from the detonation of an improvised nuclear device (IND) (a.k.a. terrorist nuclear bomb) with only radiation injuries will be salvageable; however, they would require outpatient and/or inpatient care. Recognizing this, the U.S. National Marrow Donor Program (NMDP), U.S. Navy, and American Society for Blood and Marrow Transplantation (ASBMT) collaboratively developed RITN, which comprises medical centers with expertise in the management of bone marrow failure. The medical community will undoubtedly be taxed by the resulting medical surge from an IND despite the well-defined United States emergency medical system, the National Disaster Medical System; however, one area that is unique for radiological disasters is the care for casualties with acute radiation syndrome. Hematologists and oncologists purposefully expose their cancer patients to high doses of radiation and toxic chemicals for chemotherapy as they treat their patients, resulting in symptoms not unlike casualties with exposure to ionizing radiation from a radiological disaster. This makes the staff from cancer centers ideal for the specialized care that will be required for thousands of casualties following a mass casualty radiological incident. The RITN is a model for how a collaborative effort can fill a readiness gap-through its network of 76 hospitals, blood donor centers, and cord blood banks, the RITN is preparing to provide outpatient care and specialized supportive care to up to 63,000 radiological casualties

  15. Delayed Exercise Is Ineffective at Reversing Aberrant Nociceptive Afferent Plasticity or Neuropathic Pain After Spinal Cord Injury in Rats.

    PubMed

    Detloff, Megan Ryan; Quiros-Molina, Daniel; Javia, Amy S; Daggubati, Lekhaj; Nehlsen, Anthony D; Naqvi, Ali; Ninan, Vinu; Vannix, Kirsten N; McMullen, Mary-Katharine; Amin, Sheena; Ganzer, Patrick D; Houlé, John D

    2016-08-01

    Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that correlates with sensory fiber sprouting. Recent data indicate that exercise initiated early after SCI prevents the development of allodynia and modulated nociceptive afferent plasticity. This study determined if delaying exercise intervention until pain is detected would similarly ameliorate established SCI-induced pain. Adult, female Sprague-Dawley rats with a C5 unilateral contusion were separated into SCI allodynic and SCI non-allodynic cohorts at 14 or 28 days postinjury when half of each group began exercising on automated running wheels. Allodynia, assessed by von Frey testing, was not ameliorated by exercise. Furthermore, rats that began exercise with no allodynia developed paw hypersensitivity within 2 weeks. At the initiation of exercise, the SCI Allodynia group displayed marked overlap of peptidergic and non-peptidergic nociceptive afferents in the C7 and L5 dorsal horn, while the SCI No Allodynia group had scant overlap. At the end of 5 weeks of exercise both the SCI Allodynia and SCI No Allodynia groups had extensive overlap of the 2 c-fiber types. Our findings show that exercise therapy initiated at early stages of allodynia is ineffective at attenuating neuropathic pain, but rather that it induces allodynia-aberrant afferent plasticity in previously pain-free rats. These data, combined with our previous results, suggest that there is a critical therapeutic window when exercise therapy may be effective at treating SCI-induced allodynia and that there are postinjury periods when exercise can be deleterious. PMID:26671215

  16. Delayed Exercise Is Ineffective at Reversing Aberrant Nociceptive Afferent Plasticity or Neuropathic Pain After Spinal Cord Injury in Rats.

    PubMed

    Detloff, Megan Ryan; Quiros-Molina, Daniel; Javia, Amy S; Daggubati, Lekhaj; Nehlsen, Anthony D; Naqvi, Ali; Ninan, Vinu; Vannix, Kirsten N; McMullen, Mary-Katharine; Amin, Sheena; Ganzer, Patrick D; Houlé, John D

    2016-08-01

    Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that correlates with sensory fiber sprouting. Recent data indicate that exercise initiated early after SCI prevents the development of allodynia and modulated nociceptive afferent plasticity. This study determined if delaying exercise intervention until pain is detected would similarly ameliorate established SCI-induced pain. Adult, female Sprague-Dawley rats with a C5 unilateral contusion were separated into SCI allodynic and SCI non-allodynic cohorts at 14 or 28 days postinjury when half of each group began exercising on automated running wheels. Allodynia, assessed by von Frey testing, was not ameliorated by exercise. Furthermore, rats that began exercise with no allodynia developed paw hypersensitivity within 2 weeks. At the initiation of exercise, the SCI Allodynia group displayed marked overlap of peptidergic and non-peptidergic nociceptive afferents in the C7 and L5 dorsal horn, while the SCI No Allodynia group had scant overlap. At the end of 5 weeks of exercise both the SCI Allodynia and SCI No Allodynia groups had extensive overlap of the 2 c-fiber types. Our findings show that exercise therapy initiated at early stages of allodynia is ineffective at attenuating neuropathic pain, but rather that it induces allodynia-aberrant afferent plasticity in previously pain-free rats. These data, combined with our previous results, suggest that there is a critical therapeutic window when exercise therapy may be effective at treating SCI-induced allodynia and that there are postinjury periods when exercise can be deleterious.

  17. Delayed Intervention with Intermittent Hypoxia and Task Training Improves Forelimb Function in a Rat Model of Cervical Spinal Injury.

    PubMed

    Prosser-Loose, Erin J; Hassan, Atiq; Mitchell, Gordon S; Muir, Gillian D

    2015-09-15

    The reduction of motor, sensory and autonomic function below the level of an incomplete spinal cord injury (SCI) has devastating consequences. One approach to restore function is to induce neural plasticity as a means of augmenting spontaneous functional recovery. Acute intermittent hypoxia (AIH-brief exposures to reduced O2 levels alternating with normal O2 levels) elicits plasticity in respiratory and nonrespiratory somatic spinal systems, including improvements in ladder walking performance in rats with incomplete SCI. Here, we determined whether delayed treatment with AIH, with or without concomitant motor training, could improve motor recovery in a rat model of incomplete cervical SCI. In a randomized, blinded, sham-controlled study, rats were exposed to AIH for 7 days beginning at 4 weeks post-SCI, after much spontaneous recovery on a horizontal ladder-crossing task had already occurred. For up to 2 months post-treatment, AIH-treated rats made fewer footslips on the ladder task compared with sham-treated rats. Importantly, concomitant ladder-specific motor training was needed to elicit AIH-induced improvements, such that AIH-treated SCI rats receiving no motor training or nontask-specific treadmill training during the treatment week did not show improvements over sham-treated rats with SCI. AIH treatment combined with task-specific training did not improve recovery on two different reach-to-grasp tasks, however, nor on tasks involving unskilled forepaw use. In brief, our results indicate that task-specific training is needed for AIH to improve ladder performance in a rat model of incomplete cervical SCI. PMID:25664481

  18. Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury.

    PubMed

    Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won; Oh, Sang Ho; Lee, Yun-Sil; Lee, Eun-Jung; Cho, Jaeho

    2015-05-01

    Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. PMID:25797627

  19. Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells

    SciTech Connect

    Kobashigawa, Shinko; Suzuki, Keiji; Yamashita, Shunichi

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer We report first time that ionizing radiation induces mitochondrial dynamic changes. Black-Right-Pointing-Pointer Radiation-induced mitochondrial fission was caused by Drp1 localization. Black-Right-Pointing-Pointer We found that radiation causes delayed ROS from mitochondria. Black-Right-Pointing-Pointer Down regulation of Drp1 rescued mitochondrial dysfunction after radiation exposure. -- Abstract: Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial O{sub 2}{sup {center_dot}-} production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial O{sub 2}{sup {center_dot}-}. Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation.

  20. The influence of infrared radiation on short-term ultraviolet-radiation-induced injuries

    SciTech Connect

    Kaidbey, K.H.; Witkowski, T.A.; Kligman, A.M.

    1982-05-01

    Because heat has been reported to influence adversely short- and long-term ultraviolet (UV)-radiation-induced skin damage in animals, we investigated the short-term effects of infrared radiation on sunburn and on phototoxic reactions to topical methoxsalen and anthracene in human volunteers. Prior heating of the skin caused suppression of the phototoxic response to methoxsalen as evidenced by an increase in the threshold erythema dose. Heat administered either before or after exposure to UV radiation had no detectable influence on sunburn erythema or on phototoxic reactions provoked by anthracene.

  1. Autophagy confers DNA damage repair pathways to protect the hematopoietic system from nuclear radiation injury

    PubMed Central

    Lin, Weiwei; Yuan, Na; Wang, Zhen; Cao, Yan; Fang, Yixuan; Li, Xin; Xu, Fei; Song, Lin; Wang, Jian; Zhang, Han; Yan, Lili; Xu, Li; Zhang, Xiaoying; Zhang, Suping; Wang, Jianrong

    2015-01-01

    Autophagy is essentially a metabolic process, but its in vivo role in nuclear radioprotection remains unexplored. We observed that ex vivo autophagy activation reversed the proliferation inhibition, apoptosis, and DNA damage in irradiated hematopoietic cells. In vivo autophagy activation improved bone marrow cellularity following nuclear radiation exposure. In contrast, defective autophagy in the hematopoietic conditional mouse model worsened the hematopoietic injury, reactive oxygen species (ROS) accumulation and DNA damage caused by nuclear radiation exposure. Strikingly, in vivo defective autophagy caused an absence or reduction in regulatory proteins critical to both homologous recombination (HR) and non-homologous end joining (NHEJ) DNA damage repair pathways, as well as a failure to induce these proteins in response to nuclear radiation. In contrast, in vivo autophagy activation increased most of these proteins in hematopoietic cells. DNA damage assays confirmed the role of in vivo autophagy in the resolution of double-stranded DNA breaks in total bone marrow cells as well as bone marrow stem and progenitor cells upon whole body irradiation. Hence, autophagy protects the hematopoietic system against nuclear radiation injury by conferring and intensifying the HR and NHEJ DNA damage repair pathways and by removing ROS and inhibiting apoptosis. PMID:26197097

  2. Prevention of ultraviolet radiation-induced immunosuppression by sunscreen in Candida albicans-induced delayed-type hypersensitivity

    PubMed Central

    CHEN, QUAN; LI, RUNXIANG; ZHAO, XIAOXIA; LIANG, BIHUA; MA, SHAOYIN; LI, ZHENJIE; ZHU, HUILAN

    2016-01-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans-induced delayed-type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub-erythema dose of solar-simulated radiation. Delayed-type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi-quantitatively detected using Western blotting and immunohistochemical assays. The delayed-type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non-sunscreen group were 24.39 and 65.85%, respectively (P<0.01). The results of the Western blotting and immunohistochemistry showed that the expression levels of CD207 (P<0.01), CD80 (P<0.05) and CD86 (P<0.01) were higher in the sunscreen group, compared with those in the non-sunscreen group. UV exposure reduced Candida albicans antigen-induced delayed-type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells. PMID:27175551

  3. Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury.

    PubMed

    Poindexter, Shenika V; Reddy, Vishruth K; Mittal, Mukul K; Williams, Amanda M; Washington, M Kay; Harris, Elizabeth; Mah, Amanda; Hiebert, Scott W; Singh, Kshipra; Chaturvedi, Rupesh; Wilson, Keith T; Lund, P Kay; Williams, Christopher S

    2015-03-15

    Myeloid translocation genes (MTGs) are transcriptional corepressors implicated in development, malignancy, differentiation, and stem cell function. While MTG16 loss renders mice sensitive to chemical colitis, the role of MTG16 in the small intestine is unknown. Histological examination revealed that Mtg16(-/-) mice have increased enterocyte proliferation and goblet cell deficiency. After exposure to radiation, Mtg16(-/-) mice exhibited increased crypt viability and decreased apoptosis compared with wild-type (WT) mice. Flow cytometric and immunofluorescence analysis of intestinal epithelial cells for phospho-histone H2A.X also indicated decreased DNA damage and apoptosis in Mtg16(-/-) intestines. To determine if Mtg16 deletion affected epithelial cells in a cell-autonomous fashion, intestinal crypts were isolated from Mtg16(-/-) mice. Mtg16(-/-) and WT intestinal crypts showed similar enterosphere forming efficiencies when cultured in the presence of EGF, Noggin, and R-spondin. However, when Mtg16(-/-) crypts were cultured in the presence of Wnt3a, they demonstrated higher enterosphere forming efficiencies and delayed progression to mature enteroids. Mtg16(-/-) intestinal crypts isolated from irradiated mice exhibited increased survival compared with WT intestinal crypts. Interestingly, Mtg16 expression was reduced in a stem cell-enriched population at the time of crypt regeneration. This is consistent with MTG16 negatively regulating regeneration in vivo. Taken together, our data demonstrate that MTG16 loss promotes radioresistance and impacts intestinal stem cell function, possibly due to shifting cellular response away from DNA damage-induced apoptosis and towards DNA repair after injury.

  4. Spatiotemporal pattern of neuronal injury induced by DFP in rats: A model for delayed neuronal cell death following acute OP intoxication

    SciTech Connect

    Li Yonggang; Lein, Pamela J.; Liu Cuimei; Bruun, Donald A.; Tewolde, Teclemichael; Ford, Gregory; Ford, Byron D.

    2011-06-15

    Organophosphate (OP) neurotoxins cause acute cholinergic toxicity and seizures resulting in delayed brain damage and persistent neurological symptoms. Testing novel strategies for protecting against delayed effects of acute OP intoxication has been hampered by the lack of appropriate animal models. In this study, we characterize the spatiotemporal pattern of cellular injury after acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats received pyridostigmine (0.1 mg/kg, im) and atropine methylnitrate (20 mg/kg, im) prior to DFP (9 mg/kg, ip) administration. All DFP-treated animals exhibited moderate to severe seizures within minutes after DFP injection but survived up to 72 h. AChE activity was significantly depressed in the cortex, hippocampus, subcortical brain tissue and cerebellum at 1 h post-DFP injection and this inhibition persisted for up to 72 h. Analysis of neuronal injury by Fluoro-Jade B (FJB) labeling revealed delayed neuronal cell death in the hippocampus, cortex, amygdala and thalamus, but not the cerebellum, starting at 4 h and persisting until 72 h after DFP treatment, although temporal profiles varied between brain regions. At 24 h post-DFP injection, the pattern of FJB labeling corresponded to TUNEL staining in most brain regions, and FJB-positive cells displayed reduced NeuN immunoreactivity but were not immunopositive for astrocytic (GFAP), oligodendroglial (O4) or macrophage/microglial (ED1) markers, demonstrating that DFP causes a region-specific delayed neuronal injury mediated in part by apoptosis. These findings indicate the feasibility of this model for testing neuroprotective strategies, and provide insight regarding therapeutic windows for effective pharmacological intervention following acute OP intoxication. - Research Highlights: > DFP induced neuronal FJB labeling starting at 4-8 h after treatment > The pattern of DFP-induced FJB labeling closely corresponded to TUNEL staining > FJB

  5. Treatment of radiation-induced acute intestinal injury with bone marrow-derived mesenchymal stem cells

    PubMed Central

    ZHENG, KAI; WU, WEIZHEN; YANG, SHUNLIANG; HUANG, LIANGHU; CHEN, JIN; GONG, CHUNGUI; FU, ZHICHAO; LIN, RUOFEI; TAN, JIANMING

    2016-01-01

    The aim of the present study was to investigate the ability of bone marrow-derived mesenchymal stem cells (BMSCs) to repair radiation-induced acute intestinal injury, and to elucidate the underlying repair mechanism. Male Sprague-Dawley rats were subjected to whole abdominal irradiation using a single medical linear accelerator (12 Gy) and randomly assigned to two groups. Rats in the BMSC-treated group were injected with 1 ml BMSC suspension (2×106 cells/ml) via the tail vein, while the control group rats were injected with normal saline. BMSCs were identified by detecting the expression of CD29, CD90, CD34 and CD45 using flow cytometry. The expression of the cytokines stromal cell-derived factor 1 (SDF-1), prostaglandin E2 (PGE2) and interleukin (IL)-2 was detected using immunohistochemical techniques. Plasma citrulline concentrations were evaluated using an ELISA kit. Rat general conditions, including body weight, and changes in cellular morphology were also recorded. The results suggested that BMSCs exerted a protective effect on radiation-induced acute intestinal injury in rats. The histological damage was rapidly repaired in the BMSC-treated group. In addition, the BMSC-treated group showed significantly reduced radiation injury scores (P<0.01), mildly reduced body weight and plasma citrulline levels, significantly more rapid recovery (P<0.01), significantly reduced expression of the cytokines PGE2 and IL-2 (P<0.05) and significantly increased SDF-1 expression (P<0.01) compared with the control group. In summary, the present results indicate that BMSCs are able to effectively reduce inflammation and promote repair of the structure and function of intestinal tissues damaged by radiation exposure, suggesting that they may provide a promising therapeutic agent. PMID:27284330

  6. Subcutaneous Administration of Bovine Superoxide Dismutase Protects Lungs from Radiation-Induced Lung Injury

    PubMed Central

    Jackson, Isabel L.; Vujaskovic, Zeljko

    2016-01-01

    Background The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation (RT) exposure mitigates development of pulmonary toxicity in rats. Methods Female F344 rats (n=60) were divided among six experimental groups: (1) RT, single dose of 21 Gy to the right hemithorax; (2) RT+5 mg/kg bSOD; (3) RT+15 mg/kg bSOD; (4) No RT; (5) sham RT+5mg/kg bSOD; and (6) sham RT+15mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 hours postradiation. The effects of bSOD on radiation-induced lung injury were assessed by measurement of body weight, breathing frequency and histopathological changes. Immunohistochemistry was used to evaluate oxidative stress (8-OHdG+, NOX4+, nitrotyrosine+, 4HNE+ cells), macrophage activation (ED1+), and expression of profibrotic TGF-β in irradiated tissue. Results Radiation led to an increase in all evaluated parameters. Treatment with 15mg/kg bSOD significantly decreased levels of all evaluated parameters including tissue damage and breathing frequency starting 6 weeks post-radiation. Animals treated with 5 mg/kg bSOD trended toward a suppression of radiation-induced lung damage but did not reach statistical significance. Conclusions The single application of bSOD (15mg/kg) ameliorates radiation induced lung injury through suppression of ROS/RNS dependent tissue damage. PMID:26110460

  7. The protein PprI provides protection against radiation injury in human and mouse cells.

    PubMed

    Shi, Yi; Wu, Wei; Qiao, Huiping; Yue, Ling; Ren, Lili; Zhang, Shuyu; Yang, Wei; Yang, Zhanshan

    2016-01-01

    Severe acute radiation injuries are both very lethal and exceptionally difficult to treat. Though the radioresistant bacterium D. radiodurans was first characterized in 1956, genes and proteins key to its radioprotection have not yet to be applied in radiation injury therapy for humans. In this work, we express the D. radiodurans protein PprI in Pichia pastoris yeast cells transfected with the designed vector plasmid pHBM905A-pprI. We then treat human umbilical endothelial vein cells and BALB/c mouse cells with the yeast-derived PprI and elucidate the radioprotective effects the protein provides upon gamma irradiation. We see that PprI significantly increases the survival rate, antioxidant viability, and DNA-repair capacity in irradiated cells and decreases concomitant apoptosis rates and counts of damage-indicative γH2AX foci. Furthermore, we find that PprI reduces mortality and enhances bone marrow cell clone formation and white blood cell and platelet counts in irradiated mice. PprI also seems to alleviate pathological injuries to multiple organs and improve antioxidant viability in some tissues. Our results thus suggest that PprI has crucial radioprotective effects on irradiated human and mouse cells. PMID:27222438

  8. Chronological development of late radiation injury in the liver of the rat

    SciTech Connect

    Hebard, D.W.; Jackson, K.L.; Christensen, G.M.

    1980-03-01

    Surgically exteriorized left anterior liver lobes of rats were X-irradiated with 8 kR, and changes in liver weight and histology were evaluated for 40 weeks after irradiation. Irradiation prevented growth in the irradiated lobe. A decrease in irradiated lobe weight occurred approximately 14 weeks after irradiation and was associated with parenchymal cell loss. Inflammatory cell infiltration into the irradiated lobe occurred immediately after irradiation and remained constant for 12 weeks after which there was a further increase in numbers of inflammatory cells. Fibrosis was apparent by 2 weeks and exhibited a second increase in severity after 12 weeks. Nuclear injury in some parenchymal cells was apparent in the irradiated lobe, especially after 24 weeks. Concentric lamellations in the veins with compromise of their lumen became evident after the 10th week. The temporal response of these alterations and consideration of other reports on late radiation effects suggest that early liver injury (0 to 12 weeks) is associated with an autoimmune reaction while the more extensive liver injury which occurs later (16 to 40 weeks) is the result of more direct radiation damage to the vasculature.

  9. The protein PprI provides protection against radiation injury in human and mouse cells

    PubMed Central

    Shi, Yi; Wu, Wei; Qiao, Huiping; Yue, Ling; Ren, Lili; Zhang, Shuyu; Yang, Wei; Yang, Zhanshan

    2016-01-01

    Severe acute radiation injuries are both very lethal and exceptionally difficult to treat. Though the radioresistant bacterium D. radiodurans was first characterized in 1956, genes and proteins key to its radioprotection have not yet to be applied in radiation injury therapy for humans. In this work, we express the D. radiodurans protein PprI in Pichia pastoris yeast cells transfected with the designed vector plasmid pHBM905A-pprI. We then treat human umbilical endothelial vein cells and BALB/c mouse cells with the yeast-derived PprI and elucidate the radioprotective effects the protein provides upon gamma irradiation. We see that PprI significantly increases the survival rate, antioxidant viability, and DNA-repair capacity in irradiated cells and decreases concomitant apoptosis rates and counts of damage-indicative γH2AX foci. Furthermore, we find that PprI reduces mortality and enhances bone marrow cell clone formation and white blood cell and platelet counts in irradiated mice. PprI also seems to alleviate pathological injuries to multiple organs and improve antioxidant viability in some tissues. Our results thus suggest that PprI has crucial radioprotective effects on irradiated human and mouse cells. PMID:27222438

  10. Management of late radiation-induced rectal injury after treatment of carcinoma of the uterus

    SciTech Connect

    Allen-Mersh, T.G.; Wilson, E.J.; Hope-Stone, H.F.; Mann, C.V.

    1987-06-01

    Sixty-one of 1418 (4.3 per cent) patients treated with radiation for carcinoma of the uterus from 1963 to 1983 had significant radiation-induced complications of the intestine develop which required a surgical opinion considering further management. Ninety-three per cent of these complications involved the rectum. Florid proctitis resolved within two years of onset in 33 per cent of the patients who were managed conservatively while 22 per cent of the patients died of disseminated disease within the same time period. Surgical treatment was eventually necessary in 39 per cent of the patients who were initially treated conservatively for radiation induced proctitis. Rectal excision with coloanal sleeve anastomosis produced a satisfactory result in eight of 11 patients with severe radiation injury involving the rectum. The incidence of radiation-induced and malignant rectovaginal fistula were similar (1 per cent), but disease-induced symptoms tended to occur earlier after primary treatment (a median of eight months) compared with radiation-induced symptoms (a median of 16 months).

  11. Pathogenetic validation of the use of biological protective agents and early treatment in cases of radiation injury simulating radiation effects under space flight conditions

    NASA Technical Reports Server (NTRS)

    Rogozkin, V. D.; Varteres, V.; Sabo, L.; Groza, N.; Nikolov, I.

    1974-01-01

    In considering a radiation safety system for space flights, the various measures to protect man against radiation include drug prophylaxis. At the present time a great deal of experimental material has been accumulated on the prevention and treatment of radiation injuries. Antiradiation effectiveness has been established for sulfur- and nitrogen-containing substances, auxins, cyanides, polynucleotides, mucopolysaccharides, lipopolysaccharides, aminosaccharides, synthetic polymers, vitamins, hormones, amino acids and other compounds which can be divided into two basic groups - biological and chemical protective agents.

  12. [State of cardiovascular system in immediate and delayed periods following exposure of organism to ionizing radiation].

    PubMed

    Farber, Iu V; Shafirkin, A V

    1999-01-01

    Data on the progress of radiation damages and the character of shifts in the cardiovascular functioning following exposure to ionizing radiation as a function of dose were analyzed. Reviewed were experimental and clinical material, and records of periodic medical examinations of persons who had worked long with sources of ionizing radiation. A plausible character of deviations in health and working ability of cosmonauts in flight and at the end of career due to cardiovascular disorders is described. PMID:10590813

  13. An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis.

    PubMed

    Goudarzi, Maryam; Mak, Tytus D; Jacobs, Jonathan P; Moon, Bo-Hyun; Strawn, Steven J; Braun, Jonathan; Brenner, David J; Fornace, Albert J; Li, Heng-Hong

    2016-09-01

    Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. While we have previously reported on urine and serum biomarkers, here we assessed perturbations in the fecal metabolome resulting from exposure to external X radiation in vivo. The gastrointestinal (GI) system is of particular importance in radiation biodosimetry due to its constant cell renewal and sensitivity to radiation-induced injury. While the clinical GI symptoms such as pain, bloating, nausea, vomiting and diarrhea are manifested after radiation exposure, no reliable bioindicator has been identified for radiation-induced gastrointestinal injuries. To this end, we focused on determining a fecal metabolomic signature in X-ray irradiated mice. There is overwhelming evidence that the gut microbiota play an essential role in gut homeostasis and overall health. Because the fecal metabolome is tightly correlated with the composition and diversity of the microorganism in the gut, we also performed fecal 16S rRNA sequencing analysis to determine the changes in the microbial composition postirradiation. We used in-house bioinformatics tools to integrate the 16S rRNA sequencing and metabolomic data, and to elucidate the gut integrated ecosystem and its deviations from a stable host-microbiome state that result from irradiation. The 16S rRNA sequencing results indicated that radiation caused remarkable alterations of the microbiome in feces at the family level. Increased abundance of common members of Lactobacillaceae and Staphylococcaceae families, and decreased abundances of Lachnospiraceae, Ruminococcaceae and Clostridiaceae families were found after 5 and 12 Gy irradiation. The metabolomic data revealed statistically

  14. Genistein prevents ultraviolet B radiation-induced nitrosative skin injury and promotes cell proliferation.

    PubMed

    Terra, V A; Souza-Neto, F P; Frade, M A C; Ramalho, L N Z; Andrade, T A M; Pasta, A A C; Conchon, A C; Guedes, F A; Luiz, R C; Cecchini, R; Cecchini, A L

    2015-03-01

    Nitric oxide (NO) levels increase considerably after 24h of exposure of skin to ultraviolet B (UVB) radiation, which leads to nitrosative skin injury. In addition, increased NO levels after exposure to UVB radiation are associated with inhibition of cell proliferation. Compared to the UV-control group, UV-genistein at 10 mg/kg (UV-GEN10) group showed tissue protection, decreased lipid peroxide and nitrotyrosine formation, and low CAT activity. Furthermore, NO levels and iNOS labeling remained high. In this group, the reduction in lipid peroxides and nitrotyrosine was accompanied by upregulation of cell proliferation factors (Ki67 and PCNA), which indicated that prevention of nitrosative skin injury promoted cell proliferation and DNA repair. Genistein also prevented nitrosative events, inhibited ONOO(-) formation, which leads to tissue protection and cell proliferation. The UV-GEN15 group did not result in a greater protective effect compared to that with UV-GEN10 group. In the UV-GEN15 group, histological examination of the epidermis showed morphological alterations without efficient protection against lipid peroxide formation, as well as inhibition of Ki67 and PCNA, and VEGF labeling, which suggested inhibition of cell proliferation. These results help to elucidate the mechanisms underlying the photoprotective effect of genistein and reveal the importance of UVB radiation-induced nitrosative damage. PMID:25668145

  15. Genistein prevents ultraviolet B radiation-induced nitrosative skin injury and promotes cell proliferation.

    PubMed

    Terra, V A; Souza-Neto, F P; Frade, M A C; Ramalho, L N Z; Andrade, T A M; Pasta, A A C; Conchon, A C; Guedes, F A; Luiz, R C; Cecchini, R; Cecchini, A L

    2015-03-01

    Nitric oxide (NO) levels increase considerably after 24h of exposure of skin to ultraviolet B (UVB) radiation, which leads to nitrosative skin injury. In addition, increased NO levels after exposure to UVB radiation are associated with inhibition of cell proliferation. Compared to the UV-control group, UV-genistein at 10 mg/kg (UV-GEN10) group showed tissue protection, decreased lipid peroxide and nitrotyrosine formation, and low CAT activity. Furthermore, NO levels and iNOS labeling remained high. In this group, the reduction in lipid peroxides and nitrotyrosine was accompanied by upregulation of cell proliferation factors (Ki67 and PCNA), which indicated that prevention of nitrosative skin injury promoted cell proliferation and DNA repair. Genistein also prevented nitrosative events, inhibited ONOO(-) formation, which leads to tissue protection and cell proliferation. The UV-GEN15 group did not result in a greater protective effect compared to that with UV-GEN10 group. In the UV-GEN15 group, histological examination of the epidermis showed morphological alterations without efficient protection against lipid peroxide formation, as well as inhibition of Ki67 and PCNA, and VEGF labeling, which suggested inhibition of cell proliferation. These results help to elucidate the mechanisms underlying the photoprotective effect of genistein and reveal the importance of UVB radiation-induced nitrosative damage.

  16. Elemental diet as prophylaxis against radiation injury. Histological and ultrastructural studies.

    PubMed

    McArdle, A H; Wittnich, C; Freeman, C R; Duguid, W P

    1985-09-01

    We investigated whether elemental diet feeding would protect the intestine from radiation injury. Five dogs were fed an elemental diet for three days before receiving pelvic irradiation (500 rad/day for four days) and were maintained on the diet during the days of irradiation. These dogs were compared with five dogs that were fed normal kennel ration, but were treated similarly otherwise. One day and five days following completion of the radiation treatment, the dogs were anesthetized and a biopsy specimen of terminal ileum was taken for histologic and electron microscopic studies. In the dogs fed the elemental diet, there was no significant damage to the intestine seen on histological examination, and electron microscopy disclosed elongated microvilli and no organelle damage. However, both histological and electron microscopic examination of the intestine from dogs maintained on normal kennel ration showed that severe damage had occurred from the irradiation procedure. It seems, therefore, that the feeding of an elemental diet to dogs as a prophylaxis can afford protection to the intestine from the acute phase of radiation injury.

  17. β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury

    PubMed Central

    Liu, Z; Tian, H; Jiang, J; Yang, Y; Tan, S; Lin, X; Liu, H; Wu, B

    2016-01-01

    Intestinal crypt progenitor/stem (ICPS) cell apoptosis and vascular endothelial cell apoptosis are responsible for the initiation and development of ionizing radiation (IR)-evoked gastrointestinal syndrome. The signaling mechanisms underlying IR-induced ICPS cell apoptosis remain largely unclear. Our findings provide evidence that β-arrestin-2 (βarr2)-mediated ICPS cell apoptosis is crucial for IR-stimulated intestinal injury. βArr2-deficient mice exhibited decreased ICPS cell and intestinal Lgr5+ (leucine-rich repeat-containing G-protein-coupled receptor 5-positive) stem cell apoptosis, promoted crypt proliferation and reproduction, and protracted survival following lethal doses of radiation. Radioprotection in the ICPS cells isolated from βarr2-deficient mice depended on prolonged nuclear factor-κB (NF-κB) activation via direct interaction of βarr2 with IκBα and subsequent inhibition of p53-upregulated modulator of apoptosis (PUMA)-mediated mitochondrial dysfunction. Unexpectedly, βarr2 deficiency had little effect on IR-induced intestinal vascular endothelial cell apoptosis in mice. Consistently, βarr2 knockdown also provided significant radioresistance by manipulating NF-κB/PUMA signaling in Lgr5+ cells in vitro. Collectively, these observations show that targeting the βarr2/NF-κB/PUMA novel pathway is a potential radiomitigator for limiting the damaging effect of radiotherapy on the gastrointestinal system. Significance statement: acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiotherapy. The issue of whether the critical factor for the initiation of radiation-induced intestinal injury is intestinal stem cell apoptosis or endothelial cell apoptosis remains unresolved. βArrs have recently been found to be multifunctional adaptor of apoptosis. Here, we found that β-arrestin-2 (βarr2) deficiency was associated with decreased radiation-induced ICPS cell apoptosis, which prolonged survival in abdominally

  18. β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury.

    PubMed

    Liu, Z; Tian, H; Jiang, J; Yang, Y; Tan, S; Lin, X; Liu, H; Wu, B

    2016-09-01

    Intestinal crypt progenitor/stem (ICPS) cell apoptosis and vascular endothelial cell apoptosis are responsible for the initiation and development of ionizing radiation (IR)-evoked gastrointestinal syndrome. The signaling mechanisms underlying IR-induced ICPS cell apoptosis remain largely unclear. Our findings provide evidence that β-arrestin-2 (βarr2)-mediated ICPS cell apoptosis is crucial for IR-stimulated intestinal injury. βArr2-deficient mice exhibited decreased ICPS cell and intestinal Lgr5(+) (leucine-rich repeat-containing G-protein-coupled receptor 5-positive) stem cell apoptosis, promoted crypt proliferation and reproduction, and protracted survival following lethal doses of radiation. Radioprotection in the ICPS cells isolated from βarr2-deficient mice depended on prolonged nuclear factor-κB (NF-κB) activation via direct interaction of βarr2 with IκBα and subsequent inhibition of p53-upregulated modulator of apoptosis (PUMA)-mediated mitochondrial dysfunction. Unexpectedly, βarr2 deficiency had little effect on IR-induced intestinal vascular endothelial cell apoptosis in mice. Consistently, βarr2 knockdown also provided significant radioresistance by manipulating NF-κB/PUMA signaling in Lgr5(+) cells in vitro. Collectively, these observations show that targeting the βarr2/NF-κB/PUMA novel pathway is a potential radiomitigator for limiting the damaging effect of radiotherapy on the gastrointestinal system. Significance statement: acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiotherapy. The issue of whether the critical factor for the initiation of radiation-induced intestinal injury is intestinal stem cell apoptosis or endothelial cell apoptosis remains unresolved. βArrs have recently been found to be multifunctional adaptor of apoptosis. Here, we found that β-arrestin-2 (βarr2) deficiency was associated with decreased radiation-induced ICPS cell apoptosis, which prolonged survival in

  19. Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

    SciTech Connect

    Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C.

    2013-11-01

    Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays, were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.

  20. At the core of survival: autophagy delays the onset of both apoptotic and necrotic cell death in a model of ischemic cell injury.

    PubMed

    Loos, B; Genade, S; Ellis, B; Lochner, A; Engelbrecht, A-M

    2011-06-10

    Ischemic cell injury leads to cell death. Three main morphologies have been described: apoptosis, cell death with autophagy and necrosis. Their inherent dynamic nature, a point of no return (PONR) and molecular overlap have been stressed. The relationship between a defined cell death type and the severity of injury remains unclear. The functional role of autophagy and its effects on cell death onset is largely unknown. In this study we report a differential induction of cell death, which is dependent on the severity and duration of an ischemic insult. We show that mild ischemia leads to the induction of autophagy and apoptosis, while moderate or severe ischemia induces both apoptotic and necrotic cell death without increased autophagy. The autophagic response during mild injury was associated with an ATP surge. Real-time imaging and Fluorescence Resonance Energy Transfer (FRET) revealed that increased autophagy delays the PONR of both apoptosis and necrosis significantly. Blocking autophagy shifted PONR to an earlier point in time. Our results suggest that autophagic activity directly alters intracellular metabolic parameters, responsible for maintaining mitochondrial membrane potential and cellular membrane integrity. A similar treatment also improved functional recovery in the perfused rat heart. Taken together, we demonstrate a novel finding: autophagy is implicated only in mild injury and positions the PONR in cell death. PMID:21420401

  1. Alpha Lipoic Acid Attenuates Radiation-Induced Thyroid Injury in Rats

    PubMed Central

    Jung, Jung Hwa; Jung, Jaehoon; Kim, Soo Kyoung; Woo, Seung Hoon; Kang, Ki Mun; Jeong, Bae-Kwon; Jung, Myeong Hee; Kim, Jin Hyun; Hahm, Jong Ryeal

    2014-01-01

    Exposure of the thyroid to radiation during radiotherapy of the head and neck is often unavoidable. The present study aimed to investigate the protective effect of α-lipoic acid (ALA) on radiation-induced thyroid injury in rats. Rats were randomly assigned to four groups: healthy controls (CTL), irradiated (RT), received ALA before irradiation (ALA + RT), and received ALA only (ALA, 100 mg/kg, i.p.). ALA was treated at 24 h and 30 minutes prior to irradiation. The neck area including the thyroid gland was evenly irradiated with 2 Gy per minute (total dose of 18 Gy) using a photon 6-MV linear accelerator. Greater numbers of abnormal and unusually small follicles in the irradiated thyroid tissues were observed compared to the controls and the ALA group on days 4 and 7 after irradiation. However, all pathologies were decreased by ALA pretreatment. The quantity of small follicles in the irradiated rats was greater on day 7 than day 4 after irradiation. However, in the ALA-treated irradiated rats, the numbers of small and medium follicles were significantly decreased to a similar degree as in the control and ALA-only groups. The PAS-positive density of the colloid in RT group was decreased significantly compared with all other groups and reversed by ALA pretreatment. The high activity index in the irradiated rats was lowered by ALA treatment. TGF-ß1 immunoreactivity was enhanced in irradiated rats and was more severe on the day 7 after radiation exposure than on day 4. Expression of TGF-ß1 was reduced in the thyroid that had undergone ALA pretreatment. Levels of serum pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) did not differ significantly between the all groups. This study provides that pretreatment with ALA decreased the severity of radiation-induced thyroid injury by reducing inflammation and fibrotic infiltration and lowering the activity index. Thus, ALA could be used to ameliorate radiation-induced thyroid injury. PMID:25401725

  2. HDACi Valproic Acid (VPA) and Suberoylanilide Hydroxamic Acid (SAHA) Delay but Fail to Protect against Warm Hepatic Ischemia-Reperfusion Injury

    PubMed Central

    Ruess, Dietrich A.; Probst, Moriz; Marjanovic, Goran; Wittel, Uwe A.; Hopt, Ulrich T.; Keck, Tobias; Bausch, Dirk

    2016-01-01

    Background Histone deacetylases (HDAC) catalyze N-terminal deacetylation of lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In various animal models, such as trauma/hemorrhagic shock, ischemic stroke or myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and organoprotective and promotes survival. HDACi reduce stress signaling, cell death and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver resection or transplantation increases morbidity and mortality. Assuming protective properties, the aim of this study was to investigate the effect of the HDACi VPA and SAHA on warm hepatic I/R. Material and Methods Male Wistar-Kyoto rats (age: 6–8 weeks) were randomized to VPA, SAHA, vehicle control (pre-) treatment or sham-groups and underwent partial no-flow liver ischemia for 90 minutes with subsequent reperfusion for 6, 12, 24 and 60 hours. Injury and regeneration was quantified by serum AST and ALT levels, by macroscopic aspect and (immuno-) histology. HDACi treatment efficiency, impact on MAPK/SAPK-activation and Hippo-YAP signaling was determined by Western blot. Results Treatment with HDACi significantly enhanced hyperacetylation of Histone H3-K9 during I/R, indicative of adequate treatment efficiency. Liver injury, as measured by macroscopic aspect, serum transaminases and histology, was delayed, but not alleviated in VPA and SAHA treated animals. Importantly, tissue destruction was significantly more pronounced with VPA. SAPK-activation (p38 and JNK) was reduced by VPA and SAHA in the early (6h) reperfusion phase, but augmented later on (JNK, 24h). Regeneration appeared enhanced in SAHA and VPA treated animals and was dependent on Hippo-YAP signaling. Conclusions VPA and SAHA delay warm hepatic I/R injury at least in part through modulation of SAPK-activation. However, these HDACi fail to exert organoprotective effects, in this setting. For VPA, belated damage is even aggravated. PMID:27513861

  3. Radiation-induced brain injury: low-hanging fruit for neuroregeneration.

    PubMed

    Burns, Terry C; Awad, Ahmed J; Li, Matthew D; Grant, Gerald A

    2016-05-01

    Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system. PMID:27132524

  4. Beneficial Biological Effects of Miso with Reference to Radiation Injury, Cancer and Hypertension

    PubMed Central

    Watanabe, Hiromitsu

    2013-01-01

    This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods. Moreover, the systolic blood pressure of the Dahl male rat on 2.3% NaCl was significantly increased but that of the SD rat was not. However, the blood pressures of the rats on a diet of miso or commercial control diet (MF) did not increase. Even though miso contains 2.3% NaCl, their blood pressures were as stable as those of rats fed commercial diet containing 0.3% salt. So we considered that sodium in miso might behave differently compared with NaCl alone. These biological effects might be caused by longer fermentation periods. PMID:23914051

  5. [Application of magnet laser radiation to stimulate healing of perineum injuries in the maternity patients].

    PubMed

    Rzakulieva, L M; Israfilbeĭli, S G; Gasymova, G

    2006-09-01

    The study is aimed at developing the new complex effective method of treatment with an application of magnet laser radiation as a stimulating aid in healing of perineum injuries in the maternity patients. 86 maternity patients with perineotomy and/or episiotomy were studied in treatment. The injury on the perineum was conventionally treated by antiseptics in 40 maternity patients (control group); the magnet laser therapy (MLT) by means of device "MILTA" was applied to 46 maternity patients in concomitantly with the conventional methods. The therapeutic effect was based on the combined influence of the constant magnetic field and impulsive laser radiation of the red and infra-red range on the body. The patients reported less discomfort during MLT, which promotes the decrease of pain intensity and hyperaemia instantly after 2-3 procedures. We have not observed any sutures divergence in the maternity patients who received MLT, in comparison to the control group where full divergence of sutures was registered in 2.5%, and partial--in 7.5%. The proposed complex method of treatment with the application of MLT improves the process of the healing considerably, promotes the rapid disappearance of inflammatory signs and renders analgesic effect.

  6. Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

    SciTech Connect

    Abderrahmani, Rym; Francois, Agnes; Buard, Valerie; Benderitter, Marc; Sabourin, Jean-Christophe; Crandall, David L.; Milliat, Fabien

    2009-07-01

    Purpose: To investigate effects of plasminogen activator inhibitor 1 (PAI-1) genetic deficiency and pharmacological PAI-1 inhibition with PAI-039 in a mouse model of radiation-induced enteropathy. Methods and Materials: Wild-type (Wt) and PAI-1{sup -/-} knockout mice received a single dose of 19 Gy to an exteriorized localized intestinal segment. Sham and irradiated Wt mice were treated orally with 1 mg/g of PAI-039. Histological modifications were quantified using a radiation injury score. Moreover, intestinal gene expression was monitored by real-time PCR. Results: At 3 days after irradiation, PAI-039 abolished the radiation-induced increase in the plasma active form of PAI-1 and limited the radiation-induced gene expression of transforming growth factor {beta}1 (TGF-{beta}1), CTGF, PAI-1, and COL1A2. Moreover, PAI-039 conferred temporary protection against early lethality. PAI-039 treatment limited the radiation-induced increase of CTGF and PAI-1 at 2 weeks after irradiation but had no effect at 6 weeks. Radiation injuries were less severe in PAI-1{sup -/-} mice than in Wt mice, and despite the beneficial effect, 3 days after irradiation, PAI-039 had no effects on microscopic radiation injuries compared to untreated Wt mice. Conclusions: A genetic deficiency of PAI-1 is associated with amelioration of late radiation enteropathy. Pharmacological inhibition of PAI-1 by PAI-039 positively impacts the early, acute phase increase in plasma PAI-1 and the associated radiation-induced gene expression of inflammatory/extracellular matrix proteins. Since PAI-039 has been shown to inhibit the active form of PAI-1, as opposed to the complete loss of PAI-1 in the knockout animals, these data suggest that a PAI-1 inhibitor could be beneficial in treating radiation-induced tissue injury in acute settings where PAI-1 is elevated.

  7. Silencing Egr1 Attenuates Radiation-induced Apoptosis in Normal Tissues while Killing Cancer Cells and Delaying Tumor Growth

    PubMed Central

    Zhao, Diana Yi; Jacobs, Keith M; Hallahan, Dennis E; Thotala, Dinesh

    2015-01-01

    Normal tissue toxicity reduces the therapeutic index of radiotherapy and decreases the quality of life for cancer survivors. Apoptosis is a key element of the radiation response in normal tissues like the hippocampus and small intestine, resulting in neurocognitive disorders and intestinal malabsorption. The Early Growth Response 1 (Egr1) transcription factor mediates radiation-induced apoptosis by activating the transcription of pro-apoptosis genes in response to ionizing radiation (IR). Therefore, we hypothesized that the genetic abrogation of Egr1 and the pharmacological inhibition of its transcriptional activity could attenuate radiation-induced apoptosis in normal tissues. We demonstrated that Egr1 null mice had less apoptosis in the hippocampus and intestine following irradiation as compared to their wild-type littermates. A similar result was achieved using Mithramycin A (MMA) to prevent binding of Egr1 to target promoters in the mouse intestine. Egr1 expression using shRNA dampened apoptosis and enhanced the clonogenic survival of irradiated HT22 hippocampal neuronal cells and IEC6 intestinal epithelial cells. Mechanistically, these events involved an abrogation of p53 induction by IR and an increase in the ratio of Bcl-2/Bax expression. In contrast, targeted silencing of Egr1 in two cancer cell lines (GL261 glioma cells, HCT116 colorectal cancer cells) was not radioprotective, since it reduced their growth while also sensitizing them to radiation-induced death. Further, Egr1 depletion delayed the growth of heterotopically implanted GL261 and HCT116 tumors. These results support the potential of silencing Egr1 in order to minimize the normal tissue complications associated with radiotherapy while enhancing tumor control. PMID:26206332

  8. Delayed vaginal reconstruction in the fibrotic pelvis following radiation or previous reconstruction

    SciTech Connect

    Berek, J.S.; Hacker, N.F.; Lagasse, L.D.; Smith, M.L.

    1983-06-01

    Vaginal reconstruction was performed in 14 patients who had developed vaginal stenosis secondary to extensive pelvic fibrosis after pelvic radiation therapy (12 patients) or prior vaginal reconstruction (2 patients). Sixteen procedures were performed using a split-thickness skin graft. All patients had satisfactory vaginal restoration, and 12 patients reported good vaginal function. No fistula developed as a result of the operative procedure, but one patient later developed a rectovaginal fistula resulting from tumor recurrence. Successful vaginal reconstruction can be achieved even years after initial therapy in patients who develop an obliterated vagina from previous radiation or surgery.

  9. HGF Gene Modification in Mesenchymal Stem Cells Reduces Radiation-Induced Intestinal Injury by Modulating Immunity

    PubMed Central

    Li, Yang; Yang, Yue-Feng; Xiao, Feng-Jun; Zhang, Yi-Kun; Wang, Shao-Xia; Sun, Hui-Yan; Zhang, Qun-Wei; Wu, Chu-Tse; Wang, Li-Sheng

    2015-01-01

    Background Effective therapeutic strategies to address intestinal complications after radiation exposure are currently lacking. Mesenchymal stem cells (MSCs), which display the ability to repair the injured intestine, have been considered as delivery vehicles for repair genes. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF)-gene-modified MSCs on radiation-induced intestinal injury (RIII). Methods Female 6- to 8-week-old mice were radiated locally at the abdomen with a single 13-Gy dose of radiation and then treated with saline control, Ad-HGF or Ad-Null-modified MSCs therapy. The transient engraftment of human MSCs was detected via real-time PCR and immunostaining. The therapeutic effects of non- and HGF-modified MSCs were evaluated via FACS to determine the lymphocyte immunophenotypes; via ELISA to measure cytokine expression; via immunostaining to determine tight junction protein expression; via PCNA staining to examine intestinal epithelial cell proliferation; and via TUNEL staining to detect intestinal epithelial cell apoptosis. Results The histopathological recovery of the radiation-injured intestine was significantly enhanced following non- or HGF-modified MSCs treatment. Importantly, the radiation-induced immunophenotypic disorders of the mesenteric lymph nodes and Peyer’s patches were attenuated in both MSCs-treated groups. Treatment with HGF-modified MSCs reduced the expression and secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ), increased the expression of the anti-inflammatory cytokine IL-10 and the tight junction protein ZO-1, and promoted the proliferation and reduced the apoptosis of intestinal epithelial cells. Conclusions Treatment of RIII with HGF-gene-modified MSCs reduces local inflammation and promotes the recovery of small intestinal histopathology in a mouse model. These findings might provide an effective therapeutic strategy for RIII

  10. Quantitative analysis of contrast-enhanced ultrasonography in acute radiation-induced liver injury: An animal model

    PubMed Central

    FENG, JUN; CHEN, SHU-BO; WU, SHU-JUN; SUN, PING; XIN, TIAN-YOU; CHEN, YING-ZHEN

    2015-01-01

    The aim of the present study was to examine and assess contrast-enhanced ultrasound in the early diagnosis of acute radiation-induced liver injury in a rat model. Sixty female rats were used, with 50 rats being utilized to produce an animal model of liver injury with a single dose of stereotactic X-ray irradiation of 20 Gy. Ten rats from the injury group and 2 rats from the control group were randomly selected on days 3, 7, 14, 21 and 28, and examined by contrast-enhanced ultrasound and histopathology of liver specimens. The rats were divided into four groups: the normal control group, mild, moderate, and severe radioactive liver injury groups based on the histopathological examination results. Hepatic artery arriving time (HAAT) and hepatic vein arriving time (HVAT) were recorded, and hepatic artery to vein transit time (HA-HVTT) was calculated. The time-intensity curve of liver parenchyma, the time to peak (TTP) and peak intensity (PI) were also obtained. Significant differences were observed between liver injury and control groups for PI and HA-HVTT (P<0.05). PI and HA-HVTT were shorter in the severe liver injury group compared to the mild and moderate liver injury groups (P<0.05). Compared to the control group, higher TTP was recorded in all the liver injury groups (P<0.05), and the highest TTP level was observed in the severe liver injury group compared to the mild or moderate group (P<0.05). However, no significant difference was observed between the mild and moderate groups for PI, HA-HVTT and TTP. In conclusion, the results showed that contrast-enhanced ultrasonography is useful for an earlier diagnosis in a rat model of acute radiation-induced liver injury. PMID:26640553

  11. Severe frostbite injury in a 19-year-old patient requiring amputation of both distal forearms and lower legs due to delayed rescue: a need for advanced accident collision notification systems?

    PubMed

    Kloeters, Oliver; Ryssel, Henning; Suda, Arnold J; Lehnhardt, Marcus

    2011-06-01

    Frostbite injury is a rare but severe injury especially when rescue triage is prolonged. We here report the case of a 19-year-old male patient with severe frostbite injuries requiring amputation of both distal forearms and both lower legs due to delayed admission to medical care. This case demonstrates that even mild ambient temperatures can cause deleterious injuries if the exposure time is long enough paralleling our knowledge of burn trauma. Immediate admission to medical care is, therefore, paramount and GPS-based automated accident collision notification systems would therefore be of great benefit especially in rural areas. PMID:21298278

  12. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

    PubMed

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  13. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury

    PubMed Central

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  14. Protective Effect of Lycium ruthenicum Murr. Against Radiation Injury in Mice

    PubMed Central

    Duan, Yabin; Chen, Fan; Yao, Xingchen; Zhu, Junbo; Wang, Cai; Zhang, Juanling; Li, Xiangyang

    2015-01-01

    The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L. ruthenicum high dose (8 g/kg), L. ruthenicum middle dose (4 g/kg), L. ruthenicum low dose (2 g/kg) treatment groups, for which doses were administered the third day, seventh day and 14th day after irradiation. L. ruthenicum extract was administered orally to the mice in the three treatment groups and normal saline was administered orally to the mice in the control group and model group for 14 days. The positive group was treated with amifostine (WR-2721) at 30 min before irradiation. Except for the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body at one time. Body weight, hemogram, thymus and spleen index, DNA, caspase-3, caspase-6, and P53 contents were observed at the third day, seventh day, and 14th day after irradiation. L. ruthenicum could significantly increase the total red blood cell count, hemoglobin count and DNA contents (p < 0.05). The spleen index recovered significantly by the third day and 14th day after irradiation (p < 0.05). L. ruthenicum low dose group showed a significant reduction in caspase-3 and caspase-6 of serum in mice at the third day, seventh day, and 14th day after irradiation and L. ruthenicum middle dose group experienced a reduction in caspase-6 of serum in mice by the seventh day after irradiation. L. ruthenicum could decrease the expression of P53. The results showed that L. ruthenicum had protective effects against radiation injury in mice. PMID:26193298

  15. Mitigation of Radiation Injury by Selective Stimulation of the LPA2 Receptor

    PubMed Central

    Kiss, Gyöngyi N.; Lee, Sue-Chin; Fells, James; Liu, Jiangxiong; Valentine, William J.; Fujiwara, Yuko; Emmons-Thompson, Karin; Yates, Charles R.; Sümegi, Balázs; Tigyi, Gabor

    2012-01-01

    Due to its antiapoptotic action, derivatives of the lipid mediator lysophosphatidic acid (LPA) provide potential therapeutic utility in diseases associated with programmed cell death. Apoptosis is one of the major pathophysiological processes elicited by radiation injury to the organism. Consequently, therapeutic explorations applying compounds that mimic the antiapoptotic action of LPA have begun. Here we present a brief account of our decade-long drug discovery effort aimed at developing LPA mimics with a special focus on specific agonists of the LPA2 receptor subtype, which was found to be highly effective in protecting cells from apoptosis. We describe new evidence that 2-((3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid (GRI977143), a prototypic nonlipid agonist specific to the LPA2 receptor subtype, rescues apoptotically condemned cells in vitro and in vivo from injury caused by high-dose γ-irradiation. GRI977143 shows the features of a radiomitigator because it is effective in rescuing the lives of mice from deadly levels of radiation when administered 24 h after radiation exposure. Our findings suggest that by specifically activating LPA2 receptors GRI977143 activates the ERK1/2 prosurvival pathway, effectively reduces Bax translocation to the mitochondrion, attenuates the activation of initiator and effector caspases, reduces DNA fragmentation, and inhibits PARP-1 cleavage associated with γ-irradiation-induced apoptosis. GRI977143 also inhibits bystander apoptosis elicited by soluble proapoptotic mediators produced by irradiated cells. Thus, GRI977143 can serve as a prototype scaffold for lead optimization paving the way to more potent analogs amenable for therapeutic exploration. PMID:23127512

  16. Cyclic nucleotide responses and radiation-induced mitotic delay in Physarum polycephalum

    SciTech Connect

    Daniel, J.W.; Oleinick, N.L.

    1984-02-01

    The response of the plasmodial levels of cyclic AMP and cyclic GMP in Physarum polycephalum to several putative phosphodiesterase inhibitors and to ionizing radiation has been measured. Isobutylmethylxanthine (2 mM) induces a rapid transient threefold elevation of cyclic AMP alone, with maximum response in about 10 min and return to the base line in about 30 min. Theophylline (2 mM) induces a rapid, sustained twofold elevation of cyclic GMP only. Caffeine (2mM) and Ro-20-1724 (18 ..mu..M) both elicit a rapid transient rise in cyclic AMP, resembling the isobutylmethylxanthine response, and a slow transient elevation of the cyclic GMP level. Of particular interest is the rapid threefold transient elevation of the cyclic AMP, but not of the cyclic GMP, level by ..gamma.. radiation.

  17. Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle. [60Co

    SciTech Connect

    Cairoli, V.J.; Ivankovich, A.D.; Vucicevic, D.; Patel, K.

    1982-02-01

    During anesthetic preparation of a patient who had received routine radiation therapy of sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following 60Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significant increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (25000 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.

  18. The Role of Alveolar Epithelium in Radiation-Induced Lung Injury

    PubMed Central

    Almeida, Celine; Nagarajan, Devipriya; Tian, Jian; Leal, Sofia Walder; Wheeler, Kenneth; Munley, Michael; Blackstock, William; Zhao, Weiling

    2013-01-01

    Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11–13 Gy) and fractionated doses (24–36 Gy) of 137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis. PMID:23326473

  19. IL-1 Generated Subsequent to Radiation-Induced Tissue Injury Contributes to the Pathogenesis of Radiodermatitis

    PubMed Central

    Janko, Matthew; Ontiveros, Fernando; Fitzgerald, T. J.; Deng, April; DeCicco, Maria; Rock, Kenneth L.

    2012-01-01

    Radiation injury in the skin causes radiodermatitis, a condition in which the skin becomes inflamed and the epidermis can break down. This condition causes significant morbidity and if severe it can be an independent factor that contributes to radiation mortality. Radiodermatitis is seen in some settings of radiotherapy for cancer and is also of concern as a complication post-radiation exposure from accidents or weapons, such as a “dirty bomb”. The pathogenesis of this condition is incompletely understood. Here we have developed a murine model of radiodermatitis wherein the skin is selectively injured by irradiation with high-energy electrons. Using this model we showed that the interleukin-1 (IL-1) pathway plays a significant role in the development of radiodermatitis. Mice that lack either IL-1 or the IL-1 receptor developed less inflammation and less severe pathological changes in their skin, especially at later time-points. These findings suggest that IL-1 pathway may be a potential therapeutic target for reducing the severity of radiodermatitis. PMID:22856653

  20. Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle

    SciTech Connect

    Cairoli, V.J.; Ivankovich, A.D.; Vucicevic, D.; Patel, K.

    1982-02-01

    During anesthetic preparation of a patient who had received routine radiation therapy for sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following /sup 60/Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significant increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (2500 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.

  1. Mathematics of Radiation Propagation in Planetary Atmospheres: Absorption, Refraction, Time Delay, Occultation, and Abel Inversion

    NASA Astrophysics Data System (ADS)

    Huestis, D. L.

    Forward integration calculation of air mass, refraction, and time delay requires care even for very smooth model atmospheres. The literature abounds in examples of injudicious approximations, assumptions, transformations, variable substitutions, and failures to verify that the formulas work with unlimited accuracy for simple cases and also survive challenges from mathematically pathological but physically realizable cases. A few years ago we addressed the problem of evaluation of the Chapman function for attenuation along a straight line path in an exponential atmosphere. In this presentation we will describe issues and approaches for integration over light paths curved by refraction. The inverse problem, determining the altitude profile of mass density (index of refraction) or the concentration of an individual chemical species (absorption), from occultation data, also has its mathematically interesting (i.e., difficult) aspects. Now we automatically have noise and thus statistical analysis is just as important as calculus and numerical analysis. Here we will describe a new approach of least-squares fitting occultation data to an expansion over compact basis functions. This approach, which avoids numerical differentiation and singular integrals, was originally developed to analyze laboratory imaging data.Forward integration calculation of air mass, refraction, and time delay requires care even for very smooth model atmospheres. The literature abounds in examples of injudicious approximations, assumptions, transformations, variable substitutions, and failures to verify that the formulas work with unlimited accuracy for simple cases and also survive challenges from mathematically pathological but physically realizable cases. A few years ago we addressed the problem of evaluation of the Chapman function for attenuation along a straight line path in an exponential atmosphere. In this presentation we will describe issues and approaches for integration over light paths

  2. Delayed activation of human microglial cells by high dose ionizing radiation.

    PubMed

    Chen, Hongxin; Chong, Zhao Zhong; De Toledo, Sonia M; Azzam, Edouard I; Elkabes, Stella; Souayah, Nizar

    2016-09-01

    Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation-induced degenerative outcomes. We therefore investigated the effects of γ-irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 γ rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of γ rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1α, IL-10 and TNFα. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of γ rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia. PMID:27265419

  3. Delayed Diagnosis, Leprosy Reactions, and Nerve Injury Among Individuals With Hansen's Disease Seen at a United States Clinic

    PubMed Central

    Leon, Kristoffer E.; Jacob, Jesse T.; Franco-Paredes, Carlos; Kozarsky, Phyllis E.; Wu, Henry M.; Fairley, Jessica K.

    2016-01-01

    Background. Hansen's disease (HD), or leprosy, is uncommon in the United States. We sought to describe the characteristics of patients with HD in a US clinic, including an assessment of delays in diagnosis and HD reactions, which have both been associated with nerve damage. Methods. A retrospective chart review was conducted on patients seen at an HD clinic in the southern United States between January 1, 2002 and January 31, 2014. Demographic and clinical characteristics were summarized, including delays in diagnosis, frequency of reactions, and other complications including peripheral neuropathy. Results. Thirty patients were seen during the study time period. The majority of patients were male (73%) and had multibacillary disease (70%). Brazil, Mexico, and the United States were the most frequent of the 14 countries of origin. Hansen's disease “reactions”, severe inflammatory complications, were identified among 75% of patients, and nerve damage was present at diagnosis in 36% of patients. The median length of time between symptom onset and diagnosis was long at 12 months (range, 1–96), but no single factor was associated with a delay in diagnosis. Conclusions. The diagnosis of HD was frequently delayed among patients referred to our US clinic. The high frequency of reactions and neuropathy at diagnosis suggests that further efforts at timely diagnosis and management of this often unrecognized disease is needed to prevent the long-term sequelae associated with irreversible nerve damage. PMID:27186586

  4. Radiation brain injury is reduced by the polyamine inhibitor [alpha]-difluoromethylornithine

    SciTech Connect

    Fike, J.R.; Seilhan, T.M.; Gobbel, G.T. ); Marton, L.J. )

    1994-04-01

    [alpha]-difluoromethylornithine (DFMO) was used to reduce [sup 125]I-induced brain injury in normal beagle dogs. Different DFMO doses and administration schedules were used to determine if the reduction in brain injury was dependent on dose and/or dependent upon when the drug was administered relative to the radiation treatment. Doses of DMFO of 75 mg/kg/day and 37.5 mg/kg/day given 2 days before, during and for 14 days after irradiation reduced levels of putrescine (PU) in the cerebrospinal fluid relative to controls. Volume of edema was significantly reduced by 75 mg/kg/day of DFMO before, during and after irradiation and by the same dose when the drug was started immediately after irradiation. A reduction in edema volume after 37.5 mg/kg/day of DFMO before, during and after irradiation was very near significance. Ultrafast CT studies performed on dogs that received a DFMO dose of 75 mg/kg/day before, during and after irradiation suggested that the reduce edema volume was associated with reduced vascular permeability. Volume of necrosis and volume of contrast enhancement (breakdown of the blood-brain barrier) were significantly lower than controls only after a DFMO dose of 75 mg/kg/day before, during and after irradiation. These latter data, coupled with the findings relative to edema, suggest that different mechanisms may be involved with respect to the effects of DFMO on brain injury, or that the extents of edema, necrosis and breakdown of the blood-brain barrier may depend upon different levels of polyamine depletion. The precise mechanisms by which DFMO exerts the effects observed here need to be determined. 41 refs., 5 figs.

  5. Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

    PubMed Central

    Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

    2010-01-01

    Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

  6. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    PubMed Central

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu; LaRiviere, Patrick J.; Sammani, Saad; Lussier, Yves A.; Dudek, Steven M.; Natarajan, Viswanathan; Weichselbaum, Ralph R.; Garcia, Joe G. N.

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1−/−) or with reduced expression of S1P receptors (S1PR1+/−, S1PR2−/−, and S1PR3−/−) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2×/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2×/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.—Mathew, B., Jacobson, J. R., Berdyshev, E., Huang, Y., Sun, X., Zhao, Y., Gerhold, L. M., Siegler, J., Evenoski, C., Wang, T., Zhou, T., Zaidi, R., Moreno-Vinasco, L., Bittman, R., Chen, C. T., LaRiviere, P. J., Sammani, S., Lussier, Y. A., Dudek, S. M., Natarajan, V., Weichselbaum, R. R., Garcia, J. G. N. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. PMID:21712494

  7. Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

    PubMed Central

    2013-01-01

    Background Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. Methods Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred. Results Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group. Conclusion Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients. PMID:23672582

  8. Diffusion tensor imaging of occult injury of optic radiation following optic neuritis in multiple sclerosis

    PubMed Central

    Chen, Jiafeng; Zhu, Lijun; Li, He; Lu, Ziwen; Chen, Xin; Fang, Shaokuan

    2016-01-01

    Multiple sclerosis (MS) is easily detected by routine magnetic resonance imaging (MRI). However, it is not possible to detect early or occult lesions in MS by routine MRI, and this may explain the inconsistency between the severity of the lesions found by MRI and the degree of clinical disability of patients with MS. The present study included 10 patients with relapsing-remitting MS and 10 healthy volunteers. Each patient underwent routine 3.0 T MRI, diffusion tensor imaging (DTI), and diffusion tensor tractography (DTT). Optic nerve and optic radiation were analyzed by DTI and DTT. The fractional anisotropy (FA), mean diffusivity (MD), λ//, and λ┴ values were measured. In the 10 patients with MS, 7 optic nerves were affected, and 13 optic nerves were not affected. Cranial MRI showed that optic nerve thickening and hyperintensity occurred in 2 patients with MS. In the directionally encoded color maps, a hypointensive green signal in the optic nerve was observed in 3 patients with MS. The FA values were significantly lower and the MD, λ//, and λ┴ values were significantly higher in the affected and unaffected optic nerves and optic radiations in patients with MS in comparison with controls (P<0.05). There were no significant differences in these values between the affected and unaffected optic nerves and optic radiation in patients with MS (P>0.05). Diffusion tensor imaging is sensitive in the detection of occult injury of the optic nerve and optic radiation following optic neuritis. Diffusion tensor imaging may be a useful tool for the early diagnosis, treatment and management of MS. PMID:27703508

  9. Orazipone, a locally acting immunomodulator, ameliorates intestinal radiation injury: A preclinical study in a novel rat model

    SciTech Connect

    Boerma, Marjan; Wang, Junru; Richter, Konrad K.; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-10-01

    Purpose: Intestinal radiation injury (radiation enteropathy) is relevant to cancer treatment, as well as to radiation accidents and radiation terrorism scenarios. This study assessed the protective efficacy of orazipone, a locally-acting small molecule immunomodulator. Methods and Materials: Male rats were orchiectomized, a 4-cm segment of small bowel was sutured to the inside of the scrotum, a proximal anteperistaltic ileostomy was created for intraluminal drug administration, and intestinal continuity was re-established by end-to-side anastomosis. After three weeks postoperative recovery, the intestine in the 'scrotal hernia' was exposed locally to single-dose or fractionated X-radiation. Orazipone (30 mg/kg/day) or vehicle was administered daily through the ileostomy, either during and after irradiation, or only after irradiation. Structural, cellular, and molecular aspects of intestinal radiation toxicity were assessed two weeks after irradiation. Results: Orazipone significantly ameliorated histologic injury and transforming growth factor-{beta} immunoreactivity levels, both after single-dose and fractionated irradiation. Intestinal wall thickness was significantly reduced after single-dose and nonsignificantly after fractionated irradiation. Mucosal surface area and numbers of mast cells were partially restored by orazipone after single-dose irradiation. Conclusions: This work (1) demonstrates the utility of the ileostomy rat model for intraluminal administration of response modifiers in single-dose and fractionated radiation studies; (2) shows that mucosal immunomodulation during and/or after irradiation ameliorates intestinal toxicity; and (3) highlights important differences between single-dose and fractionated radiation regimens.

  10. Gravitational time delay in orthogonally polarized radiation passing by the sun

    NASA Technical Reports Server (NTRS)

    Harwit, M.

    1979-01-01

    Two parallel investigations into the degree, if any, to which orthogonally polarized rays are deflected differently on passing through the gravitational field of the sun were previously conducted. The first involved very long and intermediate length baseline radio interferometry. The second was initially based on observations of radiation transmitted by the Pioneer 6 spacecraft, on passing behind the sun in 1968. This work was extended by using Helios-A and Helios-B spacecraft. It was calculated that the differential deflection between orthogonally polarized components is less than one part in 10 to the 7th power of the total gravitational deflection, or less than about 10 to the -7th power arc sec, in total.

  11. Gamma radiation and magnetic field mediated delay in effect of accelerated ageing of soybean.

    PubMed

    Kumar, Mahesh; Singh, Bhupinder; Ahuja, Sumedha; Dahuja, Anil; Anand, Anjali

    2015-08-01

    Soybean seeds were exposed to gamma radiation (0.5, 1, 3 and 5 kGy), static magnetic field (50, 100 and 200 mT) and a combination of gamma radiation and magnetic energy (0.5 kGy + 200 mT and 5 kGy + 50 mT) and stored at room temperature for six months. These seeds were later subjected to accelerated ageing treatment at 42 °C temperature and 95-100 % relative humidity and were compared for various physical and biochemical characteristics between the untreated and the energized treatments. Energy treatment protected the quality of stored seeds in terms of its protein and oil content . Accelerated aging conditions, however, affected the oil and protein quantity and quality of seed negatively. Antioxidant enzymes exhibited a decline in their activity during aging while the LOX activity, which reflects the rate of lipid peroxidation, in general, increased during the aging. Gamma irradiated (3 and 5 kGy) and magnetic field treated seeds (100 and 200 mT) maintained a higher catalase and ascorbate peroxidase activity which may help in efficient scavenging of deleterious free radical produced during the aging. Aging caused peroxidative changes to lipids, which could be contributed to the loss of oil quality. Among the electromagnetic energy treatments, a dose of 1-5 kGy of gamma and 100 mT, 200 mT magnetic field effectively slowed the rate of biochemical degradation and loss of cellular integrity in seeds stored under conditions of accelerated aging and thus, protected the deterioration of seed quality. Energy combination treatments did not yield any additional protection advantage. PMID:26243899

  12. Correlations between radiation-induced double strand breaks, cell division delay, and cyclin-dependent signaling in x-irradiated NIH3T3 fibroblasts

    NASA Astrophysics Data System (ADS)

    Cariveau, Mickael J.

    2005-07-01

    Molecular responses to radiation-induced DNA double strand breaks (DSB) are mediated by the phosphorylation of the histone variant H2AX which forms identifiable gamma-H2AX foci at the site of the DSB. This event is thought to be linked with the down-regulation of signaling proteins contributing to the checkpoints regulating cell cycle progression and, vis-a-vis , the induction of cell division delay. However, it is unclear whether this division delay is directly related to the number of DSB (gamma-H2AX foci) sustained by an irradiated cell and, if so, whether this number drives cells into cell cycle delay or apoptosis. For this reason, studies were conducted in the immortalized NIH/3T3 fibroblast cell in order to establish correlations between the temporal appearance of the gamma-H2AX foci (a DSB) and the expression of the cell cycle regulatory proteins, cyclin E, A, B1, and their cyclin kinase inhibitor, p21. Cell cycle kinetics and flow cytometry were used to establish radiation-induced division delay over a dose range of 1--6 Gy where a mitotic delay of 2.65 min/cGy was established. Correlations between the expression of cyclin E, A, B1, p21, and the generation of DSB were established in NIH/3T3 cells exposed to 2 or 4 Gy x-irradiation. The data suggest that the G1/S and S phase delay (cyclin E and cyclin A protein levels) are dependent on the dose of radiation while the G2/M (cyclin B1 protein levels) delay is dependent on the quantity of DSB sustained by the irradiated cell.

  13. Radiation cataracts: mechanisms involved in their long delayed occurrence but then rapid progression

    PubMed Central

    Pendergrass, William; Singh, Narendra; Schwartz, Jeffrey

    2008-01-01

    Purpose This study was directed to assess the DNA damage and DNA repair response to X-ray inflicted lens oxidative damage and to investigate the subsequent changes in lens epithelial cell (LEC) behavior in vivo that led to long delayed but then rapidly developing cataracts. Methods Two-month-old C57Bl/6 female mice received 11 Grays (Gy) of soft x-irradiation to the head only. The animals’ eyes were examined for cataract status in 30 day intervals by slit lamp over an 11 month period post-irradiation. LEC migration, DNA fragment, free DNA retention, and reactive oxygen species (ROS) presence were established in the living lenses with fluorescent dyes using laser scanning confocal microscopy (LSCM). The extent and removal of initial LEC DNA damage were determined by comet assay. Immunohistochemistry was used to determine the presence of oxidized DNA and the response of a DNA repair protein in the lenses. Results This treatment resulted in advanced cortical cataracts that developed 5–11 months post-irradiation but then appeared suddenly within a 30 day period. The initially incurred DNA strand breaks were repaired within 30 min, but DNA damage remained as shown 72 h post-irradiation by the presence of the DNA adduct, 8-hydroxyguanosine (8-OHG), and a DNA repair protein, XRCC1. This was followed months later by abnormal behavior by LEC descendant cells with abnormal differentiation and migration patterns as seen with LSCM and fluorescent dyes. Conclusions The sudden development of cortical cataracts several months post-irradiation coupled with the above findings suggests an accumulation of damaged descendants from the initially x-irradiated LECs. As these cells migrate abnormally and leave acellular lens surface sites, eventually a crisis point may arrive for lens entry of environmental O2 with resultant ROS formation that overwhelms protection by resident antioxidant enzymes and results in the coagulation of lens proteins. The events seen in this study indicate

  14. Protective Role of Rheum Tanguticum Polysaccharide 1 in Radiation- induced Intestinal Mucosal Injury

    PubMed Central

    Liu, Lin-Na; Shi, Lei; Li, Shi-Cao; Zhang, Wen-Juan; Zhang, Yan; Zhang, Zhi-Pei

    2015-01-01

    The protective effects of Rheum tanguticum polysaccharide 1 (RTP1), which is extracted from the Chinese traditional medicine Rheum tanguticum, on radiation-induced intestinal mucosal injury was investigated. Rat intestinal crypt epithelial cells (IEC-6 cells) and Sprague-Dawley rats were each divided into control, irradiated and RTP1-pretreated irradiated groups. After irradiation, cell survival was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide). assay, and the intracellular reactive oxygen species (ROS) was detected by fluorescent probe method. Apoptosis was observed by acridine orange staining, and cell cycle was analysed by flow cytometry. Histological analysis of the rat intestinal mucosa was conducted by haematoxylin and eosin staining. Irradiation at 8 Gy(Gray) decreased cell survival rate to only 54%, significantly increased intracellular ROS levels and induced apoptosis. RTP1 pretreatment significantly inhibited cell death, reduced the formation of intracellular ROS and partially inhibited apoptosis. Irradiation markedly reduced the height and quantity of rat intestinal villi, but it could be antagonised by RTP1 pretreatment. RTP1 can promote the recovery of intestinal mucosa damage, possibly by inhibiting radiation-induced intestinal epithelial apoptosis and intracellular ROS production. PMID:26330871

  15. Dietary sugar beet fiber ameliorates diarrhea as an acute gamma-radiation injury in rats.

    PubMed

    Ishizuka, S; Ito, S; Kasai, T; Hara, H

    2000-09-01

    Gamma radiation induces diarrhea as an acute injury. We have studied whether ingestion of sugar beet fiber influences radiation-induced diarrhea. Abdominal irradiation with gamma rays induced diarrhea in male Wistar/ST rats from 2 to 7 days after a single sublethal dose. The body weight of the irradiated rats was decreased temporarily at 4 days after irradiation regardless of the ingestion of sugar beet fiber. At day 8, it returned to almost the same level as that of unirradiated rats. A change in daily food intake resulted in a pattern similar to that for body weight. Dietary sugar beet fiber had little significant effect on the changes in body weight and daily food intake, and its ingestion significantly decreased gamma-ray-induced diarrhea. Changes in biochemical and histological parameters in intestinal mucosa (small intestine, cecum and colon) were not greatly influenced by the ingestion of sugar beet fiber through the periods of diarrhea. It was concluded that dietary sugar beet fiber ameliorated the diarrhea induced by abdominal irradiation. We suggest that the inhibitory effect of the ingestion of sugar beet fiber is due to its effects on the luminal environment, such as support for bacterial function in the luminal contents in the colon of animals that ingest sugar beet fiber.

  16. Anti-CD31 delays platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arterioles.

    PubMed

    Rosenblum, W I; Murata, S; Nelson, G H; Werner, P K; Ranken, R; Harmon, R C

    1994-07-01

    The arterioles on the surface of the mouse brain (pial arterioles) were observed by in vivo microscopy. A focus of minor endothelial damage was produced in a single pial arteriole in each mouse by briefly exposing the site to a helium neon laser after an intravenous injection of Evans blue. Mice were injected 10 minutes before injury with a monoclonal antibody (MAb) to mouse CD31, also known as platelet endothelial cell adhesion molecule. This treatment doubled (P < .01) the time required for the laser to produce a recognizable platelet aggregate. In additional experiments, an MAb to mouse CD61 and an MAb to mouse intercellular adhesion molecule 1 had no effect. The data support previous observations indicating that platelet adhesion/aggregation in this model is induced by endothelial injury without exposure of basal lamina. The data are consistent with the hypothesis that the endothelial injury exposes or activates a platelet endothelial cell adhesion molecule on the endothelium which is blocked by the MAb directed against CD31. This may be the first demonstration of an effect of an anti-platelet endothelial cell adhesion molecule on platelet endothelial cell adhesion molecule on platelet adhesion/aggregation in vivo. PMID:8030753

  17. Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

    SciTech Connect

    Chapman, Christopher H.; Nagesh, Vijaya; Sundgren, Pia C.; Buchtel, Henry; Chenevert, Thomas L.; Junck, Larry; Lawrence, Theodore S.; Tsien, Christina I.; Cao, Yue

    2012-04-01

    Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results: In both structures, longitudinal diffusivity ({lambda}{sub Double-Vertical-Line }) decreased and perpendicular diffusivity ({lambda}{sub Up-Tack }) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum {lambda}{sub Up-Tack} at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in {lambda}{sub Up-Tack} at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum {lambda}{sub Double-Vertical-Line} (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum {lambda}{sub Double-Vertical-Line} changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.

  18. Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy

    SciTech Connect

    Anscher, Mitchell S. . E-mail: anscher@radonc.duke.edu; Chen, Liguang; Rabbani, Zahid; Kang Song; Larrier, Nicole; Huang Hong; Samulski, Thaddeus V.; Dewhirst, Mark W.; Brizel, David M.; Folz, Rodney J.; Vujaskovic, Zeljko

    2005-05-01

    The ability to optimize treatments for cancer on the basis of relative risks for normal tissue injury has important implications in oncology, because higher doses of radiation might, in some diseases, improve both local control and survival. To achieve this goal, a thorough understanding of the molecular mechanisms responsible for radiation-induced toxicity will be essential. Recent research has demonstrated that ionizing radiation triggers a series of genetic and molecular events, which might lead to chronic persistent alterations in the microenvironment and an aberrant wound-healing response. Disrupted epithelial-stromal cell communication might also be important. With the application of a better understanding of fundamental biology to clinical practice, new approaches to treating and preventing normal tissue injury can focus on correcting these disturbed molecular processes.

  19. Recombinant human neuregulin-1β is protective against radiation-induced myocardial cell injury.

    PubMed

    Zhou, Qiang; Hu, Wenbing; Fei, Xinxiong; Huang, Xuqun; Chen, Xi; Zhao, Deqing; Huang, Jun; Jiang, Lan; Wang, Gangsheng

    2016-07-01

    The aim of the present study was to investigate the role of recombinant human neuregulin-1β (rhNRG-1β) in the repair of the radiation-induced damage of myocardial cells and the underlying mechanism. Rats were divided into the radiotherapy alone group, the rhNRG-1β group (radiotherapy with rhNRG‑1β treatment) and the Herceptin group (radiotherapy with Herceptin treatment), and their myocardial cells were analyzed. The morphology of the myocardial cells was observed under an optical microscope, and the expression of γ‑H2AX and p53 was analyzed using immunohistochemistry and western blot analysis. Damage to the myocardial cells was identified in the three groups following radiation treatment, which was identified by cell swelling and altered morphology. The integrated optical density values of γ‑H2AX in the radiotherapy alone, rhNRG‑1β and Herceptin groups were 50.96±5.548, 27.63±10.61 and 76.12±2.084, respectively. The OD of the radiotherapy alone group was significantly higher than that of the rhNRG‑1β treated group (P<0.0001), and the value of the Herceptin group was significantly higher than that of the radiotherapy alone group (P<0.0001). The p53 level in the rhNRG‑1β group was less than that of the radiotherapy alone group (P<0.001), and was higher in the Herceptin group compared with the radiotherapy alone group (P<0.0001). Thus, rhNRG‑1β can ameliorate radiotherapy-induced myocardial cell injury, predominantly by enhancing myocardial cell DNA repair, inhibiting cell apoptosis and improving myocardial function. The results of this study in myocardial cells suggest that patients with thoracic cancer may benefit from treatment with rhNRG‑1β for the repair of the radiation-induced damage of myocardial cells. PMID:27150576

  20. Computed Tomography Appearance of Early Radiation Injury to the Lung: Correlation With Clinical and Dosimetric Factors

    SciTech Connect

    Jenkins, Peter; Welsh, Anne

    2011-09-01

    Purpose: To systematically assess the spectrum of radiologic changes in the lung after radiation therapy for non-small-cell lung cancer. Methods and Materials: We reviewed the cases of 146 patients treated with radical radiotherapy at our institution. All patients had computed tomography (CT) scans performed 3 months after completion of therapy. Radiographic appearances were categorized using a standard grading system. The association of these abnormalities with pretreatment factors and clinical radiation pneumonitis (RP) was investigated. Results: New intrapulmonary abnormalities were seen in 92 patients (63%). These were ground-glass opacity in 16 (11%), patchy consolidation in 19 (13%), and diffuse consolidation in 57 (39%). Twenty-five patients (17%) developed clinical symptoms of RP. Although 80% of the patients with RP had areas of consolidation seen on the posttreatment CT scan, the majority (74%) of patients with such radiographic changes were asymptomatic. For patients with lung infiltrates, the minimum isodose encompassing the volume of radiologic abnormality was usually {>=}27 Gy. Traditional dose-volume metrics, pulmonary function tests, and the coadministration of angiotensin converting enzyme inhibitors (ACE-I) were all strongly correlated with the presence of radiologic injury on univariate analysis (p {<=} 0.002). There was also an inverse correlation between prior smoking history and CT scan changes (p = 0.02). On multivariate analysis, dosimetric parameters and the use of ACE-I retained significance (p = 0.005). Conclusions: Our findings suggest that there is substantial interindividual variation in lung radiosensitivity. ACE-I prevented the radiologic changes seen after high-dose radiation therapy, and their role as radioprotectants warrants further investigation.

  1. Inhibition of Notch signaling reduces the number of surviving Dclk1+ reserve crypt epithelial stem cells following radiation injury.

    PubMed

    Qu, Dongfeng; May, Randal; Sureban, Sripathi M; Weygant, Nathaniel; Chandrakesan, Parthasarathy; Ali, Naushad; Li, Linheng; Barrett, Terrence; Houchen, Courtney W

    2014-03-01

    We have previously reported that doublecortin-like kinase 1 (Dclk1) is a putative intestinal stem cell (ISC) marker. In this report, we evaluated the use of Dclk1 as a marker of surviving ISCs in response to treatment with high-dose total body irradiation (TBI). Both apoptotic and mitotic Dclk1(+) cells were observed 24 h post-TBI associated with a corresponding loss of intestinal crypts observed at 84 h post-TBI. Although the Notch signaling pathway plays an important role in regulating proliferation and lineage commitment within the intestine, its role in ISC function in response to severe genotoxic injury is not yet fully understood. We employed the microcolony assay to functionally assess the effects of Notch inhibition with difluorophenacetyl-l-alanyl-S-phenylglycine t-butyl ester (DAPT) on intestinal crypt stem cell survival following severe (>8 Gy) radiation injury. Following treatment with DAPT, we observed a nearly 50% reduction in the number of surviving Dclk1(+) crypt epithelial cells at 24 h after TBI and similar reduction in the number of surviving small intestinal crypts at 84 h. These data indicate that inhibition of Notch signaling decreases ISC survival following radiation injury, suggesting that the Notch signaling pathway plays an important role in ISC-mediated crypt regeneration. These results also suggest that crypt epithelial cell Dclk1 expression can be used as one potential marker to evaluate the early survival of ISCs following severe radiation injury.

  2. Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury.

    PubMed

    Talley Watts, Lora; Long, Justin Alexander; Boggs, Robert Cole; Manga, Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2016-01-15

    Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration-grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3 h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24 h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3 h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24 h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored. PMID:25961471

  3. Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury.

    PubMed

    Talley Watts, Lora; Long, Justin Alexander; Boggs, Robert Cole; Manga, Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2016-01-15

    Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration-grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3 h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24 h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3 h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24 h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored.

  4. Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model

    PubMed Central

    Felice, Peter A.; Gong, Bo; Ahsan, Salman; Deshpande, Sagar S.; Nelson, Noah S.; Donneys, Alexis; Tchanque-Fossuo, Catherine; Morris, Michael D.

    2015-01-01

    Despite its therapeutic role in head and neck cancer, radiation administration degrades the biomechanical properties of bone and can lead to pathologic fracture and osteoradionecrosis. Our laboratories have previously demonstrated that prophylactic amifostine administration preserves the biomechanical properties of irradiated bone and that Raman spectroscopy accurately evaluates bone composition ex vivo. As such, we hypothesize that Raman spectroscopy can offer insight into the temporal and mechanical effects of both irradiation and amifostine administration on bone to potentially predict and even prevent radiation-induced injury. Male Sprague–Dawley rats (350–400 g) were randomized into control, radiation exposure (XRT), and amifostine pre-treatment/radiation exposure groups (AMF-XRT). Irradiated animals received fractionated 70 Gy radiation to the left hemi-mandible, while AMF-XRT animals received amifostine just prior to radiation. Hemi-mandibles were harvested at 18 weeks after radiation, analyzed via Raman spectroscopy, and compared with specimens previously harvested at 8 weeks after radiation. Mineral (ρ958) and collagen (ρ1665) depolarization ratios were significantly lower in XRT specimens than in AMF-XRT and control specimens at both 8 and 18 weeks. amifostine administration resulted in a full return of mineral and collagen depolarization ratios to normal levels at 18 weeks. Raman spectroscopy demonstrates radiation-induced damage to the chemical composition and ultrastructure of bone while amifostine prophylaxis results in a recovery towards normal, native mineral and collagen composition and orientation. These findings have the potential to impact on clinical evaluations and interventions by preventing or detecting radiation-induced injury in patients requiring radiotherapy as part of a treatment regimen. PMID:25319554

  5. Therapeutic effects of bone marrow-derived mesenchymal stem cells on radiation-induced lung injury.

    PubMed

    Xia, Chengcheng; Chang, Pengyu; Zhang, Yuyu; Shi, Weiyan; Liu, Bin; Ding, Lijuan; Liu, Min; Gao, Ling; Dong, Lihua

    2016-02-01

    Radiation-induced lung injury (RILI) is a fatal condition featured by interstitial pneumonitis and fibrosis. Mesenchymal stem cells (MSCs) have been widely used for treating RILI in rodent models. In the present study, we aimed to investigate whether the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on RILI were in a dose-dependent manner. A total of 100 mice were randomly divided into: a control group (n=25), subject to lung irradiation and injection of phosphate-buffered solution (PBS) via the tail vein; and the hBM-MSC group, subject to lung irradiation followed by injection of a low dose (1x103 hBM-MSCs/g), medium dose (5x103 hBM-MSCs/g) and high dose (1x104 hBM-MSCs/g) of hBM-MSCs in PBS through the tail vein, respectively. After sacrifice, the pulmonary tissues were subject to hematoxylin and eosin (H&E) staining, Masson's trichrome staining and immunohistochemical staining to investigate the pathological changes. Immunofluorescent staining was performed to evaluate the differentiation capacity of hBM-MSCs in vivo by analyzing the expression of SPC and PECAM. hBM-MSCs improved the survival rate and histopathological features in the irradiated mice, especially in the low-dose group. Marked decrease in collagen deposition was noted in the irradiated mice treated using a low dose of hBM-MSCs. In addition, hBM-MSCs attenuated secretion and expression of IL-10 and increased the expression of TNF-α. Furthermore, hBM-MSCs had the potential to differentiate into functional cells upon lung injury. Low-dose hBM-MSCs contributed to functional recovery in mice with RILI. PMID:26717975

  6. In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy

    PubMed Central

    Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

    2016-01-01

    Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

  7. In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy.

    PubMed

    Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

    2016-01-01

    Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

  8. Early or Delayed Intervention for Bile Duct Injuries following Laparoscopic Cholecystectomy? A Dilemma Looking for an Answer.

    PubMed

    Felekouras, Evangelos; Petrou, Athanasios; Neofytou, Kyriakos; Moris, Demetrios; Dimitrokallis, Nikolaos; Bramis, Konstantinos; Griniatsos, John; Pikoulis, Emmanouil; Diamantis, Theodoros

    2015-01-01

    Background. To evaluate the effect of timing of management and intervention on outcomes of bile duct injury. Materials and Methods. We retrospectively analyzed 92 patients between 1991 and 2011. Data concerned patient's demographic characteristics, type of injury (according to Strasberg classification), time to referral, diagnostic procedures, timing of surgical management, and final outcome. The endpoint was the comparison of postoperative morbidity (stricture, recurrent cholangitis, required interventions/dilations, and redo reconstruction) and mortality between early (less than 2 weeks) and late (over 12 weeks) surgical reconstruction. Results. Three patients were treated conservatively, two patients were treated with percutaneous drainage, and 13 patients underwent PTC or ERCP. In total 74 patients were operated on in our unit. 58 of them underwent surgical reconstruction by end-to-side Roux-en-Y hepaticojejunostomy, 11 underwent primary bile duct repair, and the remaining 5 underwent more complex procedures. Of the 56 patients, 34 patients were submitted to early reconstruction, while 22 patients were submitted to late reconstruction. After a median follow-up of 93 months, there were two deaths associated with BDI after LC. Outcomes after early repairs were equal to outcomes after late repairs when performed by specialists. Conclusions. Early repair after BDI results in equal outcomes compared with late repair. BDI patients should be referred to centers of expertise and experience.

  9. Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases

    SciTech Connect

    Ohguri, Takayuki . E-mail: ogurieye@med.uoeh-u.ac.jp; Imada, Hajime; Kohshi, Kiyotaka; Kakeda, Shingo; Ohnari, Norihiro; Morioka, Tomoaki; Nakano, Keita; Konda, Nobuhide; Korogi, Yukunori

    2007-01-01

    Purpose: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). Methods and Materials: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). Radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. Results: Radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). Conclusions: The present study showed a potential value of prophylactic HBO for Radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit.

  10. Epoxyeicosatrienoic acid analogue mitigates kidney injury in a rat model of radiation nephropathy.

    PubMed

    Hye Khan, Md Abdul; Fish, Brian; Wahl, Geneva; Sharma, Amit; Falck, John R; Paudyal, Mahesh P; Moulder, John E; Imig, John D; Cohen, Eric P

    2016-04-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by CYP epoxygenases, and EETs are kidney protective in multiple pathologies. We determined the ability of an EET analogue, EET-A, to mitigate experimental radiation nephropathy. The kidney expression of the EET producing enzyme CYP2C11 was lower in rats that received total body irradiation (TBI rat) compared with non-irradiated control. At 12 weeks after TBI, the rats had higher systolic blood pressure and impaired renal afferent arteriolar function compared with control, and EET-A or captopril mitigated these abnormalities. The TBI rats had 3-fold higher blood urea nitrogen (BUN) compared with control, and EET-A or captopril decreased BUN by 40-60%. The urine albumin/creatinine ratio was increased 94-fold in TBI rats, and EET-A or captopril attenuated that increase by 60-90%. In TBI rats, nephrinuria was elevated 30-fold and EET-A or captopril decreased it by 50-90%. Renal interstitial fibrosis, tubular and glomerular injury were present in the TBI rats, and each was decreased by EET-A or captopril. We further demonstrated elevated renal parenchymal apoptosis in TBI rats, which was mitigated by EET-A or captopril. Additional studies revealed that captopril or EET-A mitigated renal apoptosis by acting on the p53/Fas/FasL (Fas ligand) apoptotic pathway. The present study demonstrates a novel EET analogue-based strategy for mitigation of experimental radiation nephropathy by improving renal afferent arteriolar function and by decreasing renal apoptosis.

  11. EPOXYEICOSATRIENOIC ACID ANALOG MITIGATES KIDNEY INJURY IN A RAT MODEL OF RADIATION NEPHROPATHY

    PubMed Central

    Khan, Abdul Hye; Fish, Brian; Wahl, Geneva; Sharma, Amit; Falck, John R.; Paudyal, Mahesh P.; Moulder, John E.; Imig, John D.; Cohen, Eric P.

    2016-01-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by CYP-epoxygenases, and EETs are kidney protective in multiple pathologies. We determined the ability of an EET analog, EET-A, to mitigate experimental radiation nephropathy. The kidney expression of the EET producing enzyme CYP2C11 was lower in rats that received total body irradiation (TBI rat) compared to non-irradiated control. At 12 weeks after TBI, the rats had higher systolic blood pressure and impaired renal afferent arteriolar function compared to control, and EET-A or captopril mitigated these abnormalities. The TBI rats had 3-fold higher blood urea nitrogen compared to control, and EET-A or captopril decreased BUN by 40–60%. The urine albumin/creatinine ratio was increased 94-fold in TBI rats, and EET-A or captopril attenuated that increase by 60–90%. In TBI rats, nephrinuria was elevated 30-fold and EET-A or captopril decreased it by 50–90%. Renal interstitial fibrosis, tubular, and glomerular injury were present in the TBI rats, and each was decreased by EET-A or captopril. We further demonstrated elevated renal parenchymal apoptosis in TBI rats, which EET-A or captopril mitigated. Additional studies revealed that captopril or EET-A mitigated renal apoptosis by acting on p53/Fas/FasL apoptotic pathway. Overall, this study demonstrates a novel EET-analog based strategy for mitigation of experimental radiation nephropathy by improving renal afferent arteriolar function and by decreasing renal apoptosis. PMID:26772189

  12. Aerosol-induced lung injuries observed by synchrotron radiation X-ray phase-contrast imaging technique

    NASA Astrophysics Data System (ADS)

    Yue, Weisheng; Zhang, Guilin; Liu, Ping; Sun, Jianqi; Hwu, Yeukuang; Je, Jung Ho; Tan, Mingguang; Li, Yan

    2007-09-01

    Adverse health effects are associated with the inhalation of a variety of atmospheric particles. To study the lung injuries caused by aerosol PM2.5, synchrotron radiation (SR) X-ray phase-contrast imaging technique was used. Nude mice were inoculated with PM2.5 samples collected from suburban area (JD), industrial area (BS) and traffic tunnel (DPQ) of Shanghai. From X-ray phase-contrast images of lung tissues, apart from blood vessels and structures of alveoli, even hemorrhage spots of several microns caused by the inflammation were clearly observed. The studies showed that the PM2.5 samples collected from the traffic tunnel (DPQ) produced higher level of lung injury, followed by the aerosol samples collected from industrial area (BS) and suburban area (JD). Our studies also helped us to understand the process of lung injuries caused by aerosol particles.

  13. Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair

    PubMed Central

    MacLeod, Amanda S; Rudolph, Ross; Corriden, Ross; Ye, Ivan; Garijo, Olivia; Havran, Wendy L

    2014-01-01

    Skin-resident T cells have been shown to play important roles in tissue homeostasis and wound repair, however, their role in ultraviolet radiation (UVR)-mediated skin injury and subsequent tissue regeneration is less clear. Here, we demonstrate that acute UVR rapidly activates skin-resident T cells in humans and dendritic epidermalγδ T cells (DETC) in mice through mechanisms involving the release of ATP from keratinocytes. Following UVR, extracellular ATP leads to an increase in CD69 expression, proliferation, and IL-17 production, and to changes in DETC morphology. Furthermore, we find that the purinergic receptor P2X7 and caspase-1 are necessary for UVR-induced IL-1 production in keratinocytes, which increases IL-17 secretion by DETC. IL-17, in turn, induces epidermal TNF related weak inducer of apoptosis (TWEAK) and Growth arrest and DNA damage associated gene 45 (GADD45), two molecules linked to the DNA repair response. Finally, we demonstrate that DETC and human skin-resident T cells limit DNA damage in keratinocytes. Together, our findings establish a novel role for skin-resident T cells in the UVR-associated DNA repair response and underscore the importance of skin-resident T cells to overall skin regeneration. PMID:24808367

  14. The Protective Effects of 5-Methoxytryptamine-α-lipoic Acid on Ionizing Radiation-Induced Hematopoietic Injury.

    PubMed

    Li, Deguan; Tian, Zhenyuan; Tang, Weisheng; Zhang, Junling; Lu, Lu; Sun, Zhaojin; Zhou, Zewei; Fan, Feiyue

    2016-06-14

    Antioxidants are prospective radioprotectors because of their ability to scavenge radiation-induced reactive oxygen species (ROS). The hematopoietic system is widely studied in radiation research because of its high radiosensitivity. In the present study, we describe the beneficial effects of 5-methoxytryptamine-α-lipoic acid (MLA), which was synthesized from melatonin and α-lipoic acid, against radiation-induced hematopoietic injury. MLA administration significantly enhanced the survival rate of mice after 7.2 Gy total body irradiation. The results showed that MLA not only markedly increased the numbers and clonogenic potential of hematopoietic cells but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, MLA decreased the levels of ROS in hematopoietic cells by inhibiting NOX4 expression. These data demonstrate that MLA prevents radiation-induced hematopoietic syndrome by increasing the number and function of and by inhibiting DNA damage and ROS production in hematopoietic cells. These data suggest MLA is beneficial for the protection of radiation injuries.

  15. Adverse event reporting and developments in radiation biology after normal tissue injury: International Atomic Energy Agency consultation

    SciTech Connect

    Chen Yuhchyau . E-mail: Yuhchyau_chen@urmc.rochester.edu; Trotti, Andy; Coleman, C. Norman; Machtay, Mitchell; Mirimanoff, Rene O.; Hay, John; O'Brien, Peter C.; El-Gueddari, Brahim; Salvajoli, Joao V.; Jeremic, Branislav

    2006-04-01

    Purpose: Recent research has enhanced our understanding of radiation injury at the molecular-cellular and tissue levels; significant strides have occurred in standardization of adverse event reporting in clinical trials. In response, the International Atomic Energy Agency, through its Division of Human Health and its section for Applied Radiation Biology and Radiotherapy, organized a consultation meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology, normal tissue reactions, and adverse event reporting. Methods and Materials: Representatives from cooperative groups of African Radiation Oncology Group, Curriculo Radioterapeutica Ibero Latino Americana, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada Clinical Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation Oncology Group held the meeting discussion. Results: Representatives of major radiotherapy groups/organizations and prominent leaders in radiotherapy discussed current understanding of normal tissue radiobiologic effects, the design and implementation of future clinical and translational projects for normal tissue injury, and the standardization of adverse-event reporting worldwide. Conclusions: The consensus was to adopt NCI comprehensive adverse event reporting terminology and grading system (CTCAE v3.0) as the new standard for all cooperative group trials. Future plans included the implementation of coordinated research projects focusing on normal tissue biomarkers and data collection methods.

  16. The Protective Effects of 5-Methoxytryptamine-α-lipoic Acid on Ionizing Radiation-Induced Hematopoietic Injury.

    PubMed

    Li, Deguan; Tian, Zhenyuan; Tang, Weisheng; Zhang, Junling; Lu, Lu; Sun, Zhaojin; Zhou, Zewei; Fan, Feiyue

    2016-01-01

    Antioxidants are prospective radioprotectors because of their ability to scavenge radiation-induced reactive oxygen species (ROS). The hematopoietic system is widely studied in radiation research because of its high radiosensitivity. In the present study, we describe the beneficial effects of 5-methoxytryptamine-α-lipoic acid (MLA), which was synthesized from melatonin and α-lipoic acid, against radiation-induced hematopoietic injury. MLA administration significantly enhanced the survival rate of mice after 7.2 Gy total body irradiation. The results showed that MLA not only markedly increased the numbers and clonogenic potential of hematopoietic cells but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, MLA decreased the levels of ROS in hematopoietic cells by inhibiting NOX4 expression. These data demonstrate that MLA prevents radiation-induced hematopoietic syndrome by increasing the number and function of and by inhibiting DNA damage and ROS production in hematopoietic cells. These data suggest MLA is beneficial for the protection of radiation injuries. PMID:27314327

  17. The Protective Effects of 5-Methoxytryptamine-α-lipoic Acid on Ionizing Radiation-Induced Hematopoietic Injury

    PubMed Central

    Li, Deguan; Tian, Zhenyuan; Tang, Weisheng; Zhang, Junling; Lu, Lu; Sun, Zhaojin; Zhou, Zewei; Fan, Feiyue

    2016-01-01

    Antioxidants are prospective radioprotectors because of their ability to scavenge radiation-induced reactive oxygen species (ROS). The hematopoietic system is widely studied in radiation research because of its high radiosensitivity. In the present study, we describe the beneficial effects of 5-methoxytryptamine-α-lipoic acid (MLA), which was synthesized from melatonin and α-lipoic acid, against radiation-induced hematopoietic injury. MLA administration significantly enhanced the survival rate of mice after 7.2 Gy total body irradiation. The results showed that MLA not only markedly increased the numbers and clonogenic potential of hematopoietic cells but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, MLA decreased the levels of ROS in hematopoietic cells by inhibiting NOX4 expression. These data demonstrate that MLA prevents radiation-induced hematopoietic syndrome by increasing the number and function of and by inhibiting DNA damage and ROS production in hematopoietic cells. These data suggest MLA is beneficial for the protection of radiation injuries. PMID:27314327

  18. Distinction Between Recurrent Glioma and Radiation Injury Using Magnetic Resonance Spectroscopy in Combination With Diffusion-Weighted Imaging

    SciTech Connect

    Zeng, Q.-S. . E-mail: nanwushan@yahoo.com; Li, C.-F.; Liu Hong; Zhen, J.-H.; Feng, D.-C.

    2007-05-01

    Purpose: The aim of this study was to explore the diagnostic effectiveness of magnetic resonance (MR) spectroscopy with diffusion-weighted imaging on the evaluation of the recurrent contrast-enhancing areas at the site of treated gliomas. Methods and Materials: In 55 patients who had new contrast-enhancing lesions in the vicinity of the previously resected and irradiated high-grade gliomas, two-dimensional MR spectroscopy and diffusion-weighted imaging were performed. Spectral data for N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipid (Lip), and lactate (Lac) were analyzed in conjunction with the apparent diffusion coefficient (ADC) in all patients. Diagnosis of these lesions was assigned by means of follow-up or histopathology. Results: The Cho/NAA and Cho/Cr ratios were significantly higher in recurrent tumor than in regions of radiation injury (p < 0.01). The ADC value and ADC ratios (ADC of contrast-enhancing lesion to matching structure in the contralateral hemisphere) were significantly higher in radiation injury regions than in recurrent tumor (p < 0.01). With MR spectroscopic data, two variables (Cho/NAA and Cho/Cr ratios) were shown to differentiate recurrent glioma from radiation injury, and 85.5% of total subjects were correctly classified into groups. However, with discriminant analysis of MR spectroscopy imaging plus diffusion-weighted imaging, three variables (Cho/NAA, Cho/Cr, and ADC ratio) were identified and 96.4% of total subjects were correctly classified. There was a significant difference between the diagnostic accuracy of the two discriminant analyses (Chi-square = 3.96, p = 0.046). Conclusion: Using discriminant analysis, this study found that MR spectroscopy in combination with ADC ratio, rather than ADC value, can improve the ability to differentiate recurrent glioma and radiation injury.

  19. Dynamic susceptibility contrast-enhanced perfusion MR imaging in late radiation-induced injury of the brain.

    PubMed

    Chan, Y L; Yeung, D K W; Leung, S F; Lee, S F; Ching, A S C

    2005-01-01

    The objective of the study was to evaluate radiation-induced cerebral injury on dynamic susceptibility contrast-enhanced (DSCE) perfusion MR imaging and study its relationship with morphological severity and disease progression. Thirty-one patients with known radiation injury to the temporal lobes where studied. Gradient and spin-echo T2-weighted, gadolinium-enhanced T1-weighted and DSCE perfusion MR imaging were obtained in the coronal plane through the anterior temporal lobe. Regions of interest where selected in the anterior temporal lobes and the superior frontal lobe as control for analysis of perfusion parameters. The mean transit time (MTT) was prolonged in both the High Dose Zone (HDZ) receiving from two-thirds to the total dose of 66-71.2 Gy, and the Intermediary Dose Zone (IDZ) receiving up to 87% of the total dose. The HDZ but not the IDZ showed a low relative cerebral blood volume (rCBV) and relative cerebral blood flow index (rCBFi). The rCBV and rCBFi were significantly lower in both HDZ and LBZ in temporal lobes with severe lesions compared to the temporal lobes with mild lesions but there was no significant difference in bolus transit parameters. The rCBV and rCBFi were significantly lower in both HDZ and IDZ of the swollen temporal lobes compared to those without swelling. It was concluded that DSCE perfusion MR imaging demonstrated a derangement in perfusion in radiation-induced cerebral injury in rCBV, rCBFi and MTT, which were related to the severity of the radiation-induced injury and the dose of irradiation delivered.

  20. Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

    PubMed Central

    Mattes, Malcolm D.; Cardinal, Jon S.; Jacobson, Geraldine M.

    2016-01-01

    Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date. PMID:27306770

  1. Delayed leukoencephalopathy of non-small cell lung cancer patients with brain metastases underwent whole brain radiation therapy.

    PubMed

    Zhong, Xiaoling; Huang, Biao; Feng, Jieying; Yang, Wanqun; Liu, Hongjun

    2015-10-01

    To explore the incidence, MR imaging findings, dynamic developing process of delayed leukoencephalopathy (DLE) in non-small cell lung cancer (NSCLC) patients with brain metastases patients who undergone whole brain radiation (WBRT) therapy, we retrospectively reviewed 48 NSCLC patients who underwent WBRT for brain metastases from January 2010 through June 2015 and had evaluable magnetic resonance imaging after treatment. The DLE were graded using a scale to evaluate T2-FLAIR (fluid attenuated image recovery) images: grade 1 = little or no white matter hyperintensity, grade 2 = limited periventricular hyperintensity and grade 3 = diffuse white matter hyperintensity. 48 NSCLC patients with brain metastases were enrolled. The median age of these patients was 55.7 years (range 33-75 years). The median follow-up was 12 months. The characteristic MR imaging of DLE in those patients was bilaterally diffuse white matter T2 hyperintensity around the periventricular areas without enhancement, sparing from U-fiber, callosum and gray matter structure. The incidence of DLE developed 6.25% (3/48), 30.00% (12/40), 48.39% (15/31), 61.90% (13/21), 85.71% (6/7), 100% (3/3) in those patients who were followed up for 3, 6, 9, 12, 24, 36 months, respectively. Through increased understanding of it, it may be possible to help clinicians develop further therapeutic strategies to maximize benefit while limiting potential long term toxicities. These data supplement existing reports regarding the late effects of WBRT in NSCLC patients with brain metastasis.

  2. Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Schnegg, Caroline Isabel

    As a result of improvements in cancer therapy and health care, the population of long-term cancer survivors is growing. For these approximately 12 million long-term cancer survivors, brain metastases are a significant risk. Fractionated partial or whole-brain irradiation (fWBI) is often required to treat both primary and metastatic brain cancer. Radiation-induced normal tissue injury, including progressive cognitive impairment, however, can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year. Recent reports indicate that radiation-induced brain injury is associated with chronic inflammatory and oxidative stress responses, as well as increased microglial activation in the brain. Anti-inflammatory drugs may, therefore, be a beneficial therapy to mitigate radiation-induced brain injury. We hypothesized that activation of peroxisomal proliferator activated receptor delta (PPARō) would prevent or ameliorate radiation-induced brain injury, including cognitive impairment, in part, by alleviating inflammatory responses in microglia. For our in vitro studies, we hypothesized that PPARō activation would prevent the radiation-induced inflammatory response in microglia following irradiation. Incubating BV-2 murine microglial cells with the (PPAR)ō agonist, L-165041, prevented the radiation-induced increase in: i) intracellular ROS generation, ii) Cox-2 and MCP-1 expression, and iii) IL-1β and TNF-α message levels. This occured, in part, through PPARō-mediated modulation of stress activated kinases and proinflammatory transcription factors. PPARō inhibited NF-κB via transrepression by physically interacting with the p65 subunit, and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular ROS generation. These data support the hypothesis that PPARō activation can modulate the radiation-induced oxidative stress and inflammatory

  3. Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing.

    PubMed

    Turk, Harmony F; Monk, Jennifer M; Fan, Yang-Yi; Callaway, Evelyn S; Weeks, Brad; Chapkin, Robert S

    2013-05-01

    Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling.

  4. Tolvaptan delays the onset of end-stage renal disease in a polycystic kidney disease model by suppressing increases in kidney volume and renal injury.

    PubMed

    Aihara, Miki; Fujiki, Hiroyuki; Mizuguchi, Hiroshi; Hattori, Katsuji; Ohmoto, Koji; Ishikawa, Makoto; Nagano, Keisuke; Yamamura, Yoshitaka

    2014-05-01

    Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial. However, it was unclear which dose of tolvaptan was optimal or whether tolvaptan was able to delay progression to end-stage renal disease (ESRD). Here we examined the relationship with aquaresis and the inhibitory effect on cyst development in short-term treatment and mortality as an index of ESRD in long-term treatment with tolvaptan using DBA/2FG-pcy mice, an animal model of nephronophthisis. With short-term treatment from 5 to 15 weeks of age, tolvaptan (0.01-0.3% via diet) dose-dependently enhanced aquaresis, prevented increases in kidney weight and cyst volume, and was associated with significant reductions in kidney cAMP levels and extracellular signal-regulated kinase activity. Maximal effects of tolvaptan on aquaresis and the prevention of development of polycystic kidney disease (PKD) were obtained at 0.1%. Interestingly, tolvaptan also dose-dependently reduced urinary neutrophil gelatinase-associated lipocalin levels in correlation with the kidney volume. With long-term treatment from 5 to 29 weeks of age, tolvaptan significantly attenuated the increase in kidney volume by up to 50% and reduced urinary albumin excretion. Furthermore, tolvaptan significantly reduced the mortality rate to 20%, compared with 60% in the control group. These data indicate that tolvaptan may delay the onset of ESRD in PKD by suppressing the increases in kidney volume and renal injury, providing a promising treatment for PKD. PMID:24570071

  5. Tolvaptan delays the onset of end-stage renal disease in a polycystic kidney disease model by suppressing increases in kidney volume and renal injury.

    PubMed

    Aihara, Miki; Fujiki, Hiroyuki; Mizuguchi, Hiroshi; Hattori, Katsuji; Ohmoto, Koji; Ishikawa, Makoto; Nagano, Keisuke; Yamamura, Yoshitaka

    2014-05-01

    Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial. However, it was unclear which dose of tolvaptan was optimal or whether tolvaptan was able to delay progression to end-stage renal disease (ESRD). Here we examined the relationship with aquaresis and the inhibitory effect on cyst development in short-term treatment and mortality as an index of ESRD in long-term treatment with tolvaptan using DBA/2FG-pcy mice, an animal model of nephronophthisis. With short-term treatment from 5 to 15 weeks of age, tolvaptan (0.01-0.3% via diet) dose-dependently enhanced aquaresis, prevented increases in kidney weight and cyst volume, and was associated with significant reductions in kidney cAMP levels and extracellular signal-regulated kinase activity. Maximal effects of tolvaptan on aquaresis and the prevention of development of polycystic kidney disease (PKD) were obtained at 0.1%. Interestingly, tolvaptan also dose-dependently reduced urinary neutrophil gelatinase-associated lipocalin levels in correlation with the kidney volume. With long-term treatment from 5 to 29 weeks of age, tolvaptan significantly attenuated the increase in kidney volume by up to 50% and reduced urinary albumin excretion. Furthermore, tolvaptan significantly reduced the mortality rate to 20%, compared with 60% in the control group. These data indicate that tolvaptan may delay the onset of ESRD in PKD by suppressing the increases in kidney volume and renal injury, providing a promising treatment for PKD.

  6. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    SciTech Connect

    Dong, Lihua; Cui, Jingkun; Tang, Fengjiao; Cong, Xiaofeng; Han, Fujun

    2015-04-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  7. Delayed traumatic diaphragmatic hernia

    PubMed Central

    Lu, Jing; Wang, Bo; Che, Xiangming; Li, Xuqi; Qiu, Guanglin; He, Shicai; Fan, Lin

    2016-01-01

    Abstract Background: Traumatic diaphragmatic hernias (TDHs) are sometimes difficult to identify at an early stage and can consequently result in diagnostic delays with life-threatening outcomes. It is the aim of this case study to highlight the difficulties encountered with the earlier detection of traumatic diaphragmatic hernias. Methods: Clinical data of patients who received treatment for delayed traumatic diaphragmatic hernias in registers of the First Affiliated Hospital of Xi’an Jiaotong University from 1998 to 2014 were analyzed retrospectively. Results: Six patients were included in this study. Left hemidiaphragm was affected in all of them. Most of the patients had a history of traffic accident and 1 a stab-penetrating injury. The interval from injury to developing symptoms ranged from 2 to 11 years (median 5 years). The hernial contents included the stomach, omentum, small intestine, and colon. Diaphragmatic injury was missed in all of them during the initial managements. All patients received operations once the diagnosis of delayed TDH was confirmed, and no postoperative mortality was detected. Conclusions: Delayed TDHs are not common, but can lead to serious consequences once occurred. Early detection of diaphragmatic injuries is crucial. Surgeons should maintain a high suspicion for injuries of the diaphragm in cases with abdominal or lower chest traumas, especially in the initial surgical explorations. We emphasize the need for radiographical follow-up to detect diaphragmatic injuries at an earlier stage. PMID:27512848

  8. Radiation enteritis

    MedlinePlus

    Radiation enteropathy; Radiation-induced small bowel injury; Post-radiation enteritis ... Radiation therapy uses high-powered x-rays, particles, or radioactive seeds to kill cancer cells. The therapy ...

  9. Pharmacological induction of transforming growth factor-beta1 in rat models enhances radiation injury in the intestine and the heart.

    PubMed

    Boerma, Marjan; Wang, Junru; Sridharan, Vijayalakshmi; Herbert, Jean-Marc; Hauer-Jensen, Martin

    2013-01-01

    Radiation therapy in the treatment of cancer is dose limited by radiation injury in normal tissues such as the intestine and the heart. To identify the mechanistic involvement of transforming growth factor-beta 1 (TGF-β1) in intestinal and cardiac radiation injury, we studied the influence of pharmacological induction of TGF-β1 with xaliproden (SR 57746A) in rat models of radiation enteropathy and radiation-induced heart disease (RIHD). Because it was uncertain to what extent TGF-β induction may enhance radiation injury in heart and intestine, animals were exposed to irradiation schedules that cause mild to moderate (acute) radiation injury. In the radiation enteropathy model, male Sprague-Dawley rats received local irradiation of a 4-cm loop of rat ileum with 7 once-daily fractions of 5.6 Gy, and intestinal injury was assessed at 2 weeks and 12 weeks after irradiation. In the RIHD model, male Sprague-Dawley rats received local heart irradiation with a single dose of 18 Gy and were followed for 6 months after irradiation. Rats were treated orally with xaliproden starting 3 days before irradiation until the end of the experiments. Treatment with xaliproden increased circulating TGF-β1 levels by 300% and significantly induced expression of TGF-β1 and TGF-β1 target genes in the irradiated intestine and heart. Various radiation-induced structural changes in the intestine at 2 and 12 weeks were significantly enhanced with TGF-β1 induction. Similarly, in the RIHD model induction of TGF-β1 augmented radiation-induced changes in cardiac function and myocardial fibrosis. These results lend further support for the direct involvement of TGF-β1 in biological mechanisms of radiation-induced adverse remodeling in the intestine and the heart.

  10. Medical Countermeasures for Radiation Exposure and Related Injuries: Characterization of Medicines, FDA-Approval Status and Inclusion into the Strategic National Stockpile

    PubMed Central

    Singh, Vijay K.; Romaine, Patricia L.P.; Seed, Thomas M.

    2015-01-01

    Abstract World events over the past decade have highlighted the threat of nuclear terrorism as well as an urgent need to develop radiation countermeasures for acute radiation exposures and subsequent bodily injuries. An increased probability of radiological or nuclear incidents due to detonation of nuclear weapons by terrorists, sabotage of nuclear facilities, dispersal and exposure to radioactive materials, and accidents provides the basis for such enhanced radiation exposure risks for civilian populations. Although the search for suitable radiation countermeasures for radiation-associated injuries was initiated more than half a century ago, no safe and effective radiation countermeasure for the most severe of these injuries, namely acute radiation syndrome (ARS), has been approved by the United States Food and Drug Administration (FDA). The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. In this communication, the authors have listed and reviewed the status of radiation countermeasures that are currently available for use, or those that might be used for exceptional nuclear/radiological contingencies, plus a limited few medicines that show early promise but still remain experimental in nature and unauthorized for human use by the FDA. PMID:25905522

  11. Medical Countermeasures for Radiation Exposure and Related Injuries: Characterization of Medicines, FDA-Approval Status and Inclusion into the Strategic National Stockpile.

    PubMed

    Singh, Vijay K; Romaine, Patricia L P; Seed, Thomas M

    2015-06-01

    World events over the past decade have highlighted the threat of nuclear terrorism as well as an urgent need to develop radiation countermeasures for acute radiation exposures and subsequent bodily injuries. An increased probability of radiological or nuclear incidents due to detonation of nuclear weapons by terrorists, sabotage of nuclear facilities, dispersal and exposure to radioactive materials, and accidents provides the basis for such enhanced radiation exposure risks for civilian populations. Although the search for suitable radiation countermeasures for radiation-associated injuries was initiated more than half a century ago, no safe and effective radiation countermeasure for the most severe of these injuries, namely acute radiation syndrome (ARS), has been approved by the United States Food and Drug Administration (FDA). The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. In this communication, the authors have listed and reviewed the status of radiation countermeasures that are currently available for use, or those that might be used for exceptional nuclear/radiological contingencies, plus a limited few medicines that show early promise but still remain experimental in nature and unauthorized for human use by the FDA. PMID:25905522

  12. Clinical, dosimetric, and radiographic correlation of radiation injury involving the brainstem and the medial temporal lobes following stereotactic radiotherapy for neoplasms of central skull base.

    PubMed

    Schipani, Stefano; Jain, Rajan; Shah, Keyur; Rock, Jack P; Movsas, Benjamin; Rosenblum, Mark; Ryu, Samuel

    2010-06-01

    Stereotactic Radiotherapy (SRT) is more commonly used for skull base tumors in conjunction with the technical development of radiation intensity modulation. Purpose of this study is to correlate clinical and radiographic characteristics of delayed radiation injury (RI) occurring around central skull base following SRT with SRT dosimetric data. Total of six patients were identified to have developed RI in the vicinity of SRT target volume out of 141 patients who received SRT in he center or near-center of the skull base. The images and medical records were retrospectively reviewed. The analysis was performed for RI location, time of development, imaging and clinical characteristics and evolution of RI and correlated with SRT dosimetric analysis using image fusion with follow-up MRI scans. Mean follow-up time was 24 +/- 9 months. During the follow-up period, twelve sites of RI were found in 6 patients. They were clinically symptomatic in 4/6 patients (66.6%) at median 12.5 months after SRT. Mean time interval between SRT and detection of RI was 9 +/- 3, 18.5 +/- 5, and 13.5 months for brainstem, temporal lobe, and cerebellum/labyrinth lesions, respectively. All RI lesions were included in the region of high SRT doses. After steroid and symptomatic treatment, 50% of RI lesions showed complete response, and 40% showed partial response. RI can occur around the skull base because of irregular shape of target tumor, its close proximity to normal brain parenchyma, and inhomogeneity of dose distribution. Brainstem lesions occurred earlier than temporal lobe RI. The majority of the RI lesions, not mixed with the tumor in this study, showed radiographic and clinical improvement with steroid and symptomatic treatments. PMID:20376551

  13. Recruitment of transplanted dermal multipotent stem cells to sites of injury in rats with combined radiation and wound injury by interaction of SDF-1 and CXCR4.

    PubMed

    Zong, Zhao-Wen; Cheng, Tian-Min; Su, Yong-Ping; Ran, Xin-Ze; Shen, Yue; Li, Nan; Ai, Guo-Ping; Dong, Shi-Wu; Xu, Hui

    2008-10-01

    Systemic transplantation of dermal multipotent stem cells has been shown to accelerate both hematopoietic recovery and wound healing in rats with combined radiation and wound injury. In the present study, we explored the mechanisms governing the recruitment of dermal multipotent stem cells to the sites of injury in rats with combined injury. Male dermal multipotent stem cells were transplanted into female rats, and using quantitative real-time PCR for the sex-determining region of Y chromosome, it was found that the amounts of dermal multipotent stem cells in irradiated bone marrow and wounded skin were far greater than those in normal bone marrow and skin (P < 0.01). However, incubation of dermal multipotent stem cells with AMD3100 before transplantation, which specifically blocks binding of stromal cell-derived factor 1 (SDF-1) to its receptor CXCR4, diminished the recruitment of dermal multipotent stem cells to the irradiated bone marrow and wounded skin by 58 +/- 4% and 60 +/- 4%, respectively (P < 0.05). In addition, it was confirmed that the expression of SDF-1 in irradiated bone marrow and wounded skin was up-regulated compared to that in their normal counterparts, and in vitro analysis revealed that irradiated bone marrow and wounded skin extracts had a strong chemotactic effect on dermal multipotent stem cells but that the effect decreased significantly when dermal multipotent stem cells were preincubated with AMD3100 (P < 0.05). These data suggest that transplanted dermal multipotent stem cells were recruited more frequently to the irradiated bone marrow and wounded skin than normal bone marrow and skin and that the interactions of SDF-1 and CXCR4 played a crucial role in this process.

  14. Model Development and Use of ACE Inhibitors for Preclinical Mitigation of Radiation-Induced Injury to Multiple Organs

    PubMed Central

    Medhora, Meetha; Gao, Feng; Wu, Qingping; Molthen, Robert C.; Jacobs, Elizabeth R.; Moulder, John E.; Fish, Brian L.

    2014-01-01

    The NIH/NIAID initiated a countermeasure program to develop mitigators for radiation-induced injuries from a radiological attack or nuclear accident. We have previously characterized and demonstrated mitigation of single organ injuries, such as radiation pneumonitis, pulmonary fibrosis or nephropathy by angiotensin converting enzyme (ACE) inhibitors. Our current work extends this research to examine the potential for mitigating multiple organ dysfunctions occurring in the same irradiated rats. Using total body irradiation (TBI) followed by bone marrow transplant, we tested four doses of X radiation (11, 11.25, 11.5 and 12 Gy) to develop lethal late effects. We identified three of these doses (11, 11.25 and 11.5 Gy TBI) that were lethal to all irradiated rats by 160 days to test mitigation by ACE inhibitors of injury to the lungs and kidneys. In this study we tested three ACE inhibitors at doses: captopril (88 and 176 mg/m2/day), enalapril (18, 24 and 36 mg/m2/day) and fosinopril (60 mg/m2/day) for mitigation. Our primary end point was survival or criteria for euthanization of morbid animals. Secondary end points included breathing intervals, other assays for lung structure and function and blood urea nitrogen (BUN) to assess renal damage. We found that captopril at 176 mg/m2/day increased survival after 11 or 11.5 Gy TBI. Enalapril at 18–36 mg/m2/day improved survival at all three doses (TBI). Fosinopril at 60 mg/m2/day enhanced survival at a dose of 11 Gy, although no improvement was observed for pneumonitis. These results demonstrate the use of a single countermeasure to mitigate the lethal late effects in the same animal after TBI. PMID:25361399

  15. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice.

    PubMed

    Son, Y; Heo, K; Bae, M J; Lee, C G; Cho, W S; Kim, S D; Yang, K; Shin, I S; Lee, M Y; Kim, J S

    2015-11-01

    Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and antisperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h(-1)) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation.

  16. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    SciTech Connect

    Heravi, Mitra; Kumala, Slawomir; Rachid, Zakaria; Jean-Claude, Bertrand J.; Radzioch, Danuta; Muanza, Thierry M.

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

  17. Achieving a balance between small singlet-triplet energy splitting and high fluorescence radiative rate in a quinoxaline-based orange-red thermally activated delayed fluorescence emitter.

    PubMed

    Yu, Ling; Wu, Zhongbin; Xie, Guohua; Zhong, Cheng; Zhu, Zece; Cong, Hengjiang; Ma, Dongge; Yang, Chuluo

    2016-09-21

    A new orange-red thermally activated delayed fluorescence (TADF) emitter is designed and synthesized by incorporating a fluorine-substituted quinoxaline as an electron-acceptor and a phenoxazine as an electron-donor. The rational molecular design enables small singlet-triplet energy splitting (ΔEST) and high fluorescence radiative rate (k) for long-wavelength TADF emitters. The organic light emitting diodes (OLEDs) employing the new TADF emitter achieve maximum external quantum efficiencies (EQEs) of 13.9% and 9.0% for the vacuum- and solution-processed OLEDs, respectively.

  18. Mobilization of Circulating Vascular Progenitors in Cancer Patients Receiving External Beam Radiation in Response to Tissue Injury

    SciTech Connect

    Allan, David S. Morgan, Scott C.; Birch, Paul E.; Yang, Lin; Halpenny, Michael J.; Gunanayagam, Angelo; Li Yuhua; Eapen, Libni

    2009-09-01

    Purpose: Endothelial-like vascular progenitor cells (VPCs) are associated with the repair of ischemic tissue injury in several clinical settings. Because the endothelium is a principal target of radiation injury, VPCs may be important in limiting toxicity associated with radiotherapy (RT) in patients with cancer. Methods and Materials: We studied 30 patients undergoing RT for skin cancer (n = 5), head-and-neck cancer (n = 15), and prostate cancer (n = 10) prospectively, representing a wide range of irradiated mucosal volumes. Vascular progenitor cell levels were enumerated from peripheral blood at baseline, midway through RT, at the end of treatment, and 4 weeks after radiation. Acute toxicity was graded at each time point by use of the National Cancer Institute's Common Toxicity Criteria, version 3.0. Results: Significant increases in the proportion of CD34{sup +}/CD133{sup +} VPCs were observed after completion of RT, from 0.012% at baseline to 0.048% (p = 0.029), and the increase in this subpopulation was most marked in patients with Grade 2 peak toxicity or greater after RT (p = 0.034). Similarly, CD34{sup +}/vascular endothelial growth factor receptor 2-positive VPCs were increased after the completion of radiation therapy in comparison to baseline (from 0.014% to 0.027%, p = 0.043), and there was a trend toward greater mobilization in patients with more significant toxicity (p = 0.08). The mobilization of CD34{sup +} hematopoietic stem cells did not increase after treatment (p = 0.58), and there was no relationship with toxicity. Conclusions: We suggest that VPCs may play an important role in reducing radiation-induced tissue damage. Interventions that increase baseline VPC levels or enhance their mobilization and recruitment in response to RT may prove useful in facilitating more rapid and complete tissue healing.

  19. High-dose selenium for the mitigation of radiation injury: a pilot study in a rat model.

    PubMed

    Sieber, Fritz; Muir, Sarah A; Cohen, Eric P; North, Paula E; Fish, Brian L; Irving, Amy A; Mäder, Marylou; Moulder, John E

    2009-03-01

    The purpose of this study was to evaluate in an animal model the safety and efficacy of dietary supplementation with high doses of selenium for the mitigation of the type of radiation injury that might be sustained during a nuclear accident or an act of radiological terrorism. Age-matched male rats were exposed to 10 Gy (single dose) of total-body irradiation (TBI) followed by a syngeneic bone marrow transplant, then randomized to standard drinking water or drinking water supplemented with sodium selenite or seleno-l-methionine. At 21 weeks after TBI, most rats on standard drinking water had severe renal failure with a mean blood urea nitrogen (BUN) level of 124 +/- 29 mg/dl (geometric mean +/- SE) whereas rats on selenium-supplemented drinking water (100 microg/day) had a mean BUN level of 67 +/- 12 mg/dl. The mitigating effect of selenium was confirmed by histopathological analyses. None of the animals on high-dose selenium showed signs of selenium toxicity. Our results suggest that dietary supplementation with high-dose selenium may provide a safe, effective and practical way to mitigate radiation injury to kidneys. PMID:19267564

  20. Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

    NASA Astrophysics Data System (ADS)

    Zhang, Hong

    2016-07-01

    We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation

  1. Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury

    PubMed Central

    Saha, Subhrajit; Aranda, Evelyn; Hayakawa, Yoku; Bhanja, Payel; Atay, Safinur; Brodin, N Patrik; Li, Jiufeng; Asfaha, Samuel; Liu, Laibin; Tailor, Yagnesh; Zhang, Jinghang; Godwin, Andrew K.; Tome, Wolfgang A.; Wang, Timothy C.; Guha, Chandan; Pollard, Jeffrey W.

    2016-01-01

    WNT/β-catenin signalling is crucial for intestinal homoeostasis. The intestinal epithelium and stroma are the major source of WNT ligands but their origin and role in intestinal stem cell (ISC) and epithelial repair remains unknown. Macrophages are a major constituent of the intestinal stroma. Here, we analyse the role of macrophage-derived WNT in intestinal repair in mice by inhibiting their release using a macrophage-restricted ablation of Porcupine, a gene essential for WNT synthesis. Such Porcn-depleted mice have normal intestinal morphology but are hypersensitive to radiation injury in the intestine compared with wild-type (WT) littermates. Porcn-null mice are rescued from radiation lethality by treatment with WT but not Porcn-null bone marrow macrophage-conditioned medium (CM). Depletion of extracellular vesicles (EV) from the macrophage CM removes WNT function and its ability to rescue ISCs from radiation lethality. Therefore macrophage-derived EV-packaged WNTs are essential for regenerative response of intestine against radiation. PMID:27734833

  2. Radiation-Induced Microvascular Injury as a Mechanism of Salivary Gland Hypofunction and Potential Target for Radioprotectors.

    PubMed

    Mizrachi, Aviram; Cotrim, Ana P; Katabi, Nora; Mitchell, James B; Verheij, Marcel; Haimovitz-Friedman, Adriana

    2016-08-01

    Radiation therapy is commonly used to treat patients with head and neck squamous cell carcinoma (HNSCC). One of the major side effects of radiotherapy is injury to the salivary glands (SG), which is thought to be mediated by microvascular dysfunction leading to permanent xerostomia. The goal of this study was to elucidate the mechanism of radiation-induced microvasculature damage and its impact on SG function. We measured bovine aortic endothelial cell (BAEC) apoptosis and ceramide production in response to 5 Gy irradiation, either alone or with reactive oxygen species (ROS) scavengers. We then investigated the effect of a single 15 Gy radiation dose on murine SG function. BAECs exposed to 5 Gy underwent apoptosis with increased ceramide production, both prevented by ROS scavengers. Among the 15 Gy irradiated mice, there was considerable weight loss, alopecia and SG hypofunction manifested by reduced saliva production and lower lysozyme levels. All of these effects, except for the lysozyme levels, were prevented by pretreatment with ROS scavengers. Microvessel density was significantly lower in the SG of irradiated mice compared to the control group, and this effect was significantly attenuated by pretreatment with Tempol. This study demonstrates that radiation-induced SG hypofunction is to a large extent mediated by microvascular dysfunction involving ceramide and ROS generation. These findings strongly suggest that ROS scavengers may serve as potential radioprotectors of SG function in patients undergoing radiotherapy for HNSCC. PMID:27459704

  3. Prevention and Treatment of Functional and Structural Radiation Injury in the Rat Heart by Pentoxifylline and Alpha-Tocopherol

    SciTech Connect

    Boerma, Marjan Roberto, Kerrey A.; Hauer-Jensen, Martin

    2008-09-01

    Purpose: Radiation-induced heart disease (RIHD) is a severe side effect of thoracic radiotherapy. This study examined the effects of pentoxifylline (PTX) and {alpha}-tocopherol on cardiac injury in a rat model of RIHD. Methods and Materials: Male Sprague-Dawley rats received fractionated local heart irradiation with a daily dose of 9 Gy for 5 days and were observed for 6 months after irradiation. Rats were treated with a combination of PTX, 100 mg/kg/day, and {alpha}-tocopherol (20 IU/kg/day) and received these compounds either from 1 week before until 6 months after irradiation or starting 3 months after irradiation, a time point at which histopathologic changes become apparent in our model of RIHD. Results: Radiation-induced increases in left ventricular diastolic pressure (in mm Hg: 35 {+-} 6 after sham-irradiation, 82 {+-} 11 after irradiation) were significantly reduced by PTX and {alpha}-tocopherol (early treatment: 48 {+-} 7; late treatment: 53 {+-} 6). PTX and {alpha}-tocopherol significantly reduced deposition of collagen types I (radiation only: 3.5 {+-} 0.2 {mu}m{sup 2} per 100 {mu}m{sup 2}; early treatment: 2.7 {+-} 0.8; late treatment: 2.2 {+-} 0.2) and III (radiation only: 13.9 {+-} 0.8; early treatment: 11.0 {+-} 1.2; late treatment: 10.6 {+-} 0.8). On the other hand, radiation-induced alterations in heart/body weight ratios, myocardial degeneration, left ventricular mast cell densities, and most echocardiographic parameters were not significantly altered by PTX and {alpha}-tocopherol. Conclusions: Treatment with PTX and {alpha}-tocopherol may have beneficial effects on radiation-induced myocardial fibrosis and left ventricular function, both when started before irradiation and when started later during the process of RIHD.

  4. Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice.

    PubMed

    Kripke, M L; Morison, W L

    1986-05-01

    Exposing mice to UV radiation in the UVB range (280-320 nm) causes a selective immune suppression that contributes to the development of UVB-induced skin cancers. Among the immune responses suppressed by UVB irradiation are contact and delayed hypersensitivity reactions to haptens administered at unexposed sites. In these studies we provide evidence that delayed and contact hypersensitivity to the same hapten are not equivalent reactions and that they are suppressed in UVB-irradiated mice by 2 different mechanisms. This conclusion is based on the findings that: suppression of contact hypersensitivity could not be overcome by immunizing UVB-irradiated mice with hapten-coupled antigen-presenting cells derived from normal donors; and treatment of UVB-irradiated mice with methylprednisolone before immunization prevented the suppression of delayed hypersensitivity but had no effect on the suppression of contact hypersensitivity. The decreased ability to induce contact hypersensitivity in UVB-irradiated mice could be transferred to x-irradiated mice by reconstituting them with spleen cells from UVB-irradiated donors. The induction of hapten-specific suppressor cells, however, required both UVB irradiation and priming with hapten. Based on these results, we postulate that UVB irradiation induces a population of suppressor-inducer cells with specificity for a modified skin antigen and that this antigen serves as a carrier molecule for haptens that induce contact hypersensitivity and for tumor-specific transplantation antigens on UVB-induced tumors. PMID:3745963

  5. Delayed ejaculation

    MedlinePlus

    Ejaculatory incompetence; Sex - delayed ejaculation; Retarded ejaculation; Anejaculation; Infertility - delayed ejaculation ... include: Religious background that makes the person view sex as sinful Lack of attraction for a partner ...

  6. Consecutive CT-guided core needle tissue biopsy of lung lesions in the same dog at different phases of radiation-induced lung injury

    PubMed Central

    Yin, Zhongyuan; Deng, Sisi; Liang, Zhiwen; Wang, Qiong

    2016-01-01

    This project aimed to set up a Beagle dog model of radiation-induced lung injury in order to supply fresh lung tissue samples in the different injury phases for gene and protein research. Three dogs received 18 Gy X-ray irradiation in one fraction, another three dogs received 8 Gy in each of three fractions at weekly intervals, and one control dog was not irradiated. Acute pneumonitis was observed during the first 3 months after radiation, and chronic lung fibrosis was found during the next 4–12 months in all the dogs exposed to radiation. CT-guided core needle lung lesion biopsies were extracted from each dog five times over the course of 1 year. The dogs remained healthy after each biopsy, and 50–100 mg fresh lung lesion tissues were collected in each operation. The incidence of pneumothorax and hemoptysis was 20% and 2.8%, respectively, in the 35 tissue biopsies. A successful and stable radiation-induced lung injury dog model was established. Lung lesion tissue samples from dogs in acute stage, recovery stage and fibrosis stage were found to be sufficient to support cytology, genomics and proteomics research. This model safely supplied fresh tissue samples that would allow future researchers to more easily explore and develop treatments for radiation-induced lung injury. PMID:27422930

  7. WE-D-BRE-01: A Sr-90 Irradiation Device for the Study of Cutaneous Radiation Injury

    SciTech Connect

    Dorand, JE; Bourland, JD; Burnett, LR; Tytell, M

    2014-06-15

    Purpose: To determine dosimetric character for a custom-built Sr-90 beta irradiator designed for the study of Cutaneous Radiation Injury (CRI) in a porcine animal model. In the event of a radiological accident or terrorist event, Sr-90, a fission by-product, will likely be produced. CRI is a main concern due to the low energy and superficial penetration in tissue of beta particles from Sr-90. Seven 100 mCi plaque Sr-90 radiation sources within a custom-built irradiation device create a 40 mm diameter region of radiation-induced skin injury as part of a larger project to study the efficacy of a topical keratin-based product in CRI healing. Methods: A custom-built mobile irradiation device was designed and implemented for in vivo irradiations. Gafchromic™ EBT3 radiochromic film and a PTW Markus chamber type 23343 were utilized for dosimetric characterization of the beta fluence at the surface produced by this device. Films were used to assess 2-dimensional dose distribution and percent depth dose characteristics of the radiation field. Ion chamber measurements provided dose rate data within the field. Results: The radiation field produced by the irradiation device is homogeneous with high uniformity (∼5%) and symmetry (∼3%) with a steep dose fall-off with depth from the surface. Dose rates were determined to be 3.8 Gy/min and 3.3 Gy/min for film and ion chamber measurements, respectively. A dose rate of 3.4 Gy/min was used to calculate irradiation times for in vivo irradiations. Conclusion: The custom-built irradiation device enables the use of seven Sr-90 beta sources in an array to deliver a 40 mm diameter area of homogeneous skin dose with a dose rate that is useful for research purposes and clinically relevant for the induction of CRI. Doses of 36 and 42 Gy successfully produce Grade III CRI and are used in the study of the efficacy of KeraStat™. This project has been funded in whole or in part with Federal funds from the Biomedical Advanced Research and

  8. Delayed massive soft tissue uptake of Tc-99m MDP after radiation therapy for cancer of the breast

    SciTech Connect

    Morrison, R.T.; Steuart, R.D.

    1995-09-01

    A patient with a history of breast cancer and known lung metastases was referred for a bone scan to investigate the cause of severe neck and right shoulder pain. The bone scan showed massive uptake of the radiopharmaceutical in the soft tissue surrounding the right shoulder. A review of the patient`s history indicated that the patient had undergone radiation therapy to the right upper thorax and breast area 14 months previously and an acute radiation dermatitis of the proximal right arm and shoulder had developed. This had long since resolved. Physical examination and plain radiographs of the right shoulder and humerus failed to demonstrated any abnormality. 6 refs., 1 fig.

  9. Delayed effects of low-dose radiation on cellular immunity in atomic bomb survivors residing in the United States.

    PubMed

    Bloom, E T; Akiyama, M; Kusunoki, Y; Makinodan, T

    1987-05-01

    Several parameters of cellular immune function were assessed among persons who survived the 1945 atomic bombs in Hiroshima and Nagasaki but who now reside in the United States. The subjects in this study were exposed to various low doses (T65D) of radiation at the time of the bomb. More than half received an estimated 0 Gy (S0 group). Of those exposed to more radiation (S+ group), nearly 90% received less than 0.50 Gy (50 rad). Lymphocytes were isolated from the peripheral blood of these individuals and were assessed for the following parameters of cellular immunity: mitogenic response to phytohemagglutinin, mitogenic response to allogeneic lymphocytes, natural cell-mediated cytotoxicity (NCMC), and interferon production. In every case, the response of the S+ group was greater than that of the S0 group, although only the difference for NCMC was statistically significant. Results of studies presently being performed on A-bomb survivors residing in Hiroshima do not confirm this difference. Therefore, it is difficult to say whether the increase in natural cytotoxicity observed among the American and not the Japanese A-bomb survivors exposed to very low doses of radiation is a hormetic effect which was modulated by post-radiation environmental conditions or a result of selective migration.

  10. Potential protection of green tea polyphenols against 1800 MHz electromagnetic radiation-induced injury on rat cortical neurons.

    PubMed

    Liu, Mei-Li; Wen, Jian-Qiang; Fan, Yu-Bo

    2011-10-01

    Radiofrequency electromagnetic fields (EMF) are harmful to public health, but the certain anti-irradiation mechanism is not clear yet. The present study was performed to investigate the possible protective effects of green tea polyphenols against electromagnetic radiation-induced injury in the cultured rat cortical neurons. In this study, green tea polyphenols were used in the cultured cortical neurons exposed to 1800 MHz EMFs by the mobile phone. We found that the mobile phone irradiation for 24 h induced marked neuronal cell death in the MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide) and TUNEL (TdT mediated biotin-dUTP nicked-end labeling) assay, and protective effects of green tea polyphenols on the injured cortical neurons were demonstrated by testing the content of Bcl-2 Assaciated X protein (Bax) in the immunoprecipitation assay and Western blot assay. In our study results, the mobile phone irradiation-induced increases in the content of active Bax were inhibited significantly by green tea polyphenols, while the contents of total Bax had no marked changes after the treatment of green tea polyphenols. Our results suggested a neuroprotective effect of green tea polyphenols against the mobile phone irradiation-induced injury on the cultured rat cortical neurons.

  11. Effect of alpha-lipoic acid on radiation-induced small intestine injury in mice

    PubMed Central

    Jeong, Bae Kwon; Song, Jin Ho; Jeong, Hojin; Choi, Hoon Sik; Jung, Jung Hwa; Hahm, Jong Ryeal; Woo, Seung Hoon; Jung, Myeong Hee; Choi, Bong-Hoi; Kim, Jin Hyun; Kang, Ki Mun

    2016-01-01

    Purpose Radiation therapy is a highly effective treatment for patients with solid tumors. However, it can cause damage and inflammation in normal tissues. Here, we investigated the effects of alpha-lipoic acid (ALA) as radioprotection agent for the small intestine in a mouse model. Materials and Methods Whole abdomen was evenly irradiated with total a dose of 15 Gy. Mice were treated with either ALA (100 mg/kg, intraperitoneal injection [i.p.]) or saline (equal volume, i.p.) the prior to radiation as 100 mg/kg/day for 3 days. Body weight, food intake, histopathology, and biochemical parameters were evaluated. Results Significant differences in body weight and food intake were observed between the radiation (RT) and ALA + RT groups. Moreover, the number of crypt cells was higher in the ALA + RT group. Inflammation was decreased and recovery time was shortened in the ALA + RT group compared with the RT group. The levels of inflammation-related factors (i.e., phosphorylated nuclear factor kappa B and matrix metalloproteinase-9) and mitogen-activated protein kinases were significantly decreased in the ALA + RT group compared with those in the RT group. Conclusions ALA treatment prior to radiation decreases the severity and duration of radiation-induced enteritis by reducing inflammation, oxidative stress, and cell death. PMID:26943777

  12. Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant) Extract

    PubMed Central

    Sharma, Priyanka; Parmar, Jyoti; Sharma, Priyanka; Verma, Preeti; Goyal, P. K.

    2011-01-01

    The primary objective of this investigation is to determine the deleterious effects of sub lethal gamma radiation on testes and their possible inhibition by Tinospora cordifolia extract (TCE). For this purpose, one group of male Swiss albino mice was exposed to 7.5 Gy gamma radiation to serve as the irradiated control, while the other group received TCE (75 mg/kg b. wt./day) orally for 5 consecutive days half an hr before irradiation to serve as experimental. Exposure of animals to 7.5 Gy gamma radiation resulted into significant decrease in body weight, tissue weight, testes- body weight ratio and tubular diameter up to 15 days of irradiation. Cent percent mortality was recorded by day 17th in irradiated control, whereas all animals survived in experimental group. TCE pretreatment rendered significant increase in body weight, tissue weight, testes- body weight ratio and tubular diameter at various intervals as compared to irradiated group. Radiation induced histological lesions in testicular architecture were observed more severe in irradiated control then the experimental. TCE administration before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radio- protective potential of Tinospora cordifolia root extract in testicular constituents against gamma irradiation in mice. PMID:21350610

  13. [Modern possibilities of medicinal prophylaxis and early therapy of radiation injuries].

    PubMed

    Grebeniuk, A N; Zatsepin, V V; Nazarov, V B; Vlasenko, T N

    2011-02-01

    Medical antiradiation protection is one of the key factors determining fighting capacity of armies. The basis of medical protection in the countries of the NATO is made with the preparations used up to an irradiation (radioprotector WR-2721) and at the first time after radiating influence. The Russian system of antiradiation protection includes radioprotectors, drugs for prophylaxis and treatment of syndrome of primary reaction to an irradiation, means of early therapy of radiation injure, preparations for sorption and elimination of radionuclides, got in an organism. PMID:21770338

  14. What Are Growth Plate Injuries?

    MedlinePlus

    ... activities. Other reasons for growth plate injuries are:  Child abuse  Injury from extreme cold (for example, frostbite)  Radiation ( ... problems) treats most growth plate injuries. At other times, the child will see a pediatric orthopaedic surgeon (a doctor ...

  15. What Are Growth Plate Injuries?

    MedlinePlus

    ... activities. Other reasons for growth plate injuries are: Child abuse Injury from extreme cold (for example, frostbite) Radiation ( ... problems) treats most growth plate injuries. At other times, the child will see a pediatric orthopaedic surgeon (a doctor ...

  16. Some cell kinetic effects of combined injury with ionizing radiation and cyclophosphamide on mouse bladder urothelium.

    PubMed

    Reitan, J B

    1985-01-01

    Cyclophosphamide was given intraperitoneally to groups of eight female mice 48 h after local electron irradiation to the bladder with 0, 10 and 20 Gy respectively. The reactions in the urothelium were monitored by histology, incorporation of tritiated thymidine and flow cytometry. A wave of increased thymidine incorporation combined with an increase in the proportion of diploid S-phase cells was seen in the unirradiated bladders 24 h after the drug treatment, followed by normalization after 1 week. This response was significantly less pronounced in the irradiated animals. In the unirradiated animals a similar wave characterized by an increased proportion of octaploid cells was also seen, but this wave occurred later in the irradiated animals. Severe injury was observed in the rectum of the 20 Gy-irradiated animals. Irradiation prior to drug treatment led to only small effects, but a decreased ability for regenerative DNA synthesis after drug injury seems to persist. This affects both proliferation and the building up of polyploidy.

  17. Role of Intercellular Adhesion Molecule-1 in Radiation-Induced Brain Injury

    SciTech Connect

    Wu, K.-L.; Tu Ba; Li Yuqing; Wong, C. Shun

    2010-01-15

    Purpose: To determine the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of brain injury after irradiation (IR). Methods and Materials: We assessed the expression of ICAM-1 in mouse brain after cranial IR and determined the histopathologic and behavioral changes in mice that were either wildtype (+/+) or knockout (-/-) of the ICAM-1 gene after IR. Results: There was an early dose-dependent increase in ICAM-1 mRNA and protein expression after IR. Increased ICAM-1 immunoreactivity was observed in endothelia and glia of ICAM-1+/+ mice up to 8 months after IR. ICAM-1-/- mice showed no expression. ICAM-1+/+ and ICAM-1-/- mice showed similar vascular abnormalities at 2 months after 10-17 Gy, and there was evidence for demyelination and inhibition of hippocampal neurogenesis at 8 months after 10 Gy. After 10 Gy, irradiated ICAM-1+/+ and ICAM-1-/- mice showed similar behavioral changes at 2-6 months in open field, light-dark chamber, and T-maze compared with age-matched genotype controls. Conclusion: There is early and late upregulation of ICAM-1 in the vasculature and glia of mouse brain after IR. ICAM-1, however, does not have a causative role in the histopathologic injury and behavioral dysfunction after moderate single doses of cranial IR.

  18. Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer

    PubMed Central

    Borrego-Soto, Gissela; Ortiz-López, Rocío; Rojas-Martínez, Augusto

    2015-01-01

    Abstract Breast cancer is the most common malignancy in women. Radiotherapy is frequently used in patients with breast cancer, but some patients may be more susceptible to ionizing radiation, and increased exposure to radiation sources may be associated to radiation adverse events. This susceptibility may be related to deficiencies in DNA repair mechanisms that are activated after cell-radiation, which causes DNA damage, particularly DNA double strand breaks. Some of these genetic susceptibilities in DNA-repair mechanisms are implicated in the etiology of hereditary breast/ovarian cancer (pathologic mutations in the BRCA 1 and 2 genes), but other less penetrant variants in genes involved in sporadic breast cancer have been described. These same genetic susceptibilities may be involved in negative radiotherapeutic outcomes. For these reasons, it is necessary to implement methods for detecting patients who are susceptible to radiotherapy-related adverse events. This review discusses mechanisms of DNA damage and repair, genes related to these functions, and the diagnosis methods designed and under research for detection of breast cancer patients with increased radiosensitivity. PMID:26692152

  19. The genetic basis of strain-dependent differences in the early phase of radiation injury in mouse lung

    SciTech Connect

    Franko, A.J.; Sharplin, J.; Ward, W.F.; Hinz, J.M. )

    1991-06-01

    Substantial differences between mouse strains have been reported in the lesions present in the lung during the early phase of radiation injury. Some strains show only classical pneumonitis, while other strains develop substantial fibrosis and hyaline membranes which contribute appreciably to respiratory insufficiency, in addition to pneumonitis. Other strains are intermediate between these extremes. These differences correlate with intrinsic differences in activities of lung plasminogen activator and angiotensin converting enzyme. The genetic basis of these differences was assessed by examining histologically the early reaction in lungs of seven murine hybrids available commercially after whole-thorax irradiation. Crosses between fibrosing and nonfibrosing parents were uniformly nonfibrosing, and crosses between fibrosing and intermediate parents were uniformly intermediate. No evidence of sex linkage was seen. Thus the phenotype in which fibrosis is found is controlled by autosomal recessive determinants. Strains prone to radiation-induced pulmonary fibrosis and hyaline membranes exhibited intrinsically lower activities of lung plasminogen activator and angiotensin converting enzyme than either the nonfibrosing strains or the nonfibrosing hybrid crosses. The median time of death of the hybrids was genetically determined primarily by the longest-lived parent regardless of the types of lesions expressed.

  20. Extracellular ATP enhances radiation-induced brain injury through microglial activation and paracrine signaling via P2X7 receptor.

    PubMed

    Xu, Pengfei; Xu, Yongteng; Hu, Bin; Wang, Jue; Pan, Rui; Murugan, Madhuvika; Wu, Long-Jun; Tang, Yamei

    2015-11-01

    Activation of purinergic receptors by extracellular ATP (eATP) released from injured cells has been implicated in the pathogenesis of many neuronal disorders. The P2X7 receptor (P2X7R), an ion-selective purinergic receptor, is associated with microglial activation and paracrine signaling. However, whether ATP and P2X7R are involved in radiation-induced brain injury (RBI) remains to be determined. Here, we found that the eATP level was elevated in the cerebrospinal fluid (CSF) of RBI patients and was associated with the clinical severity of the disorder. In our experimental model, radiation treatment increased the level of eATP in the supernatant of primary cultures of neurons and glial cells and in the CSF of irradiated mice. In addition, ATP administration activated microglia, induced the release of the inflammatory mediators such as cyclooxygenase-2, tumor necrosis factor α and interleukin 6, and promoted neuronal apoptosis. Furthermore, blockade of ATP-P2X7R interaction using P2X7 antagonist Brilliant Blue G or P2X7 knockdown suppressed radiation-induced microglial activation and proliferation in the hippocampus, and restored the spatial memory of irradiated mice. Finally, we found that the PI3K/AKT and nuclear factor κB mediated pathways were downstream of ATP-P2X7R signaling in RBI. Taken together, our results unveiled the critical role of ATP-P2X7R in brain damage in RBI, suggesting that inhibition of ATP-P2X7R axis might be a potential strategy for the treatment of patients with RBI. PMID:26122280

  1. Extracellular ATP enhances radiation-induced brain injury through microglial activation and paracrine signaling via P2X7 receptor.

    PubMed

    Xu, Pengfei; Xu, Yongteng; Hu, Bin; Wang, Jue; Pan, Rui; Murugan, Madhuvika; Wu, Long-Jun; Tang, Yamei

    2015-11-01

    Activation of purinergic receptors by extracellular ATP (eATP) released from injured cells has been implicated in the pathogenesis of many neuronal disorders. The P2X7 receptor (P2X7R), an ion-selective purinergic receptor, is associated with microglial activation and paracrine signaling. However, whether ATP and P2X7R are involved in radiation-induced brain injury (RBI) remains to be determined. Here, we found that the eATP level was elevated in the cerebrospinal fluid (CSF) of RBI patients and was associated with the clinical severity of the disorder. In our experimental model, radiation treatment increased the level of eATP in the supernatant of primary cultures of neurons and glial cells and in the CSF of irradiated mice. In addition, ATP administration activated microglia, induced the release of the inflammatory mediators such as cyclooxygenase-2, tumor necrosis factor α and interleukin 6, and promoted neuronal apoptosis. Furthermore, blockade of ATP-P2X7R interaction using P2X7 antagonist Brilliant Blue G or P2X7 knockdown suppressed radiation-induced microglial activation and proliferation in the hippocampus, and restored the spatial memory of irradiated mice. Finally, we found that the PI3K/AKT and nuclear factor κB mediated pathways were downstream of ATP-P2X7R signaling in RBI. Taken together, our results unveiled the critical role of ATP-P2X7R in brain damage in RBI, suggesting that inhibition of ATP-P2X7R axis might be a potential strategy for the treatment of patients with RBI.

  2. [Mild head injury in children and adults. Diagnostic challenges in the emergency department].

    PubMed

    Leidel, B A; Lindner, T; Wolf, S; Bogner, V; Steinbeck, A; Börner, N; Peiser, C; Audebert, H J; Biberthaler, P; Kanz, K-G

    2015-01-01

    Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time. PMID:25630884

  3. Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

    PubMed

    Sureban, Sripathi M; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A; Ding, Kai; Umar, Shahid; Schlosser, Michael J; Houchen, Courtney W

    2015-01-01

    Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

  4. Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury

    PubMed Central

    Sureban, Sripathi M.; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A.; Ding, Kai; Umar, Shahid; Schlosser, Michael J.; Houchen, Courtney W.

    2015-01-01

    Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis. PMID:26270561

  5. Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock.

    PubMed

    Zhang, Yong; Zhang, Jinxiang; Korff, Sebastian; Ayoob, Faez; Vodovotz, Yoram; Billiar, Timothy R

    2014-09-01

    An excessive and uncontrolled systemic inflammatory response is associated with organ failure, immunodepression, and increased susceptibility to nosocomial infection following trauma. Interleukin 6 (IL-6) plays a particularly prominent role in the host immune response after trauma with hemorrhage. However, as a result of its pleiotropic functions, the effect of IL-6 in trauma and hemorrhage is still controversial. It remains unclear whether suppression of IL-6 after hemorrhagic shock and trauma will attenuate organ injury and immunosuppression. In this study, C57BL/6 mice were treated with anti-mouse IL-6 monoclonal antibody immediately prior to resuscitation in an experimental model combining hemorrhagic shock and lower-extremity injury. Interleukin 6 levels and signaling were transiently suppressed following administrations of anti-IL-6 monoclonal antibody following hemorrhagic shock and lower-extremity injury. This resulted in reduced lung and liver injury, as well as suppression in the levels of key inflammatory mediators including IL-10, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and macrophage inhibitory protein 1α at both 6 and 24 h. Furthermore, the shift to TH2 cytokine production and suppressed lymphocyte response were partly prevented. These results demonstrate that IL-6 is not only a biomarker but also an important driver of injury-induced inflammation and immune suppression in mice. Rapid measurement of IL-6 levels in the early phase of postinjury care could be used to guide IL-6-based interventions.

  6. A case of delayed carotid cavernous fistula after facial gunshot injury presented as loss of vision with symptom resolution after endovascular closure procedure.

    PubMed

    Alagöz, Fatih; Yılmaz, Fevzi; Sönmez, Bedriye Müge; Yıldırım, Ali Erdem; Karakılıç, Muhammed Evvah

    2016-03-01

    Carotid cavernous fistulas (CCFs) are abnormal connections between the carotid artery and the cavernous sinus (CS), and can occur as a result of blunt and penetrating head injuries. While occurrence is rare, diagnosis can be made in the emergency department. Described in the present report is the case of a 26-year-old man who presented with complaints of pain, redness, blurred and loss of vision in the right eye, and swelling of the upper face due to a gunshot injury he had sustained 35 days prior. PMID:27193990

  7. Prospects for management of gastrointestinal injury associated with the acute radiation syndrome

    SciTech Connect

    Dubois, A.; Walker, R.I.

    1988-08-01

    The effect of total-body ionizing radiation on the digestive tract is dose-dependent and time-dependent. At low doses (1.5 Gy), one observes only a short prodromal syndrome consisting of nausea, vomiting, and gastric suppression. At doses greater than 6 Gy, the prodromal syndrome is more marked, and it is followed after a 2-5-day remission period by a subacute syndrome, characterized by diarrhea and hematochezia. This gastrointestinal syndrome is superimposed onto a radiation-induced bone marrow suppression. The combination of intestinal and hemopoietic syndromes results in dehydration, anemia, and infection, leading eventually to irreversible shock and death. The treatment of prodromal symptoms is based on the administration of antiemetics and gastrokinetics, although an effective treatment devoid of side effects is not yet available for human therapy. The treatment of the gastrointestinal subacute syndrome remains difficult and unsuccessful after exposure to total body doses greater than 8-10 Gy. Supportive therapy to prevent infection and dehydration may be effective if restoration or repopulation of the intestinal and bone marrow stem cells does occur. In addition, bone marrow transplantation may improve the prospect of treating the hemopoietic syndrome, although the experience gained in Chernobyl suggests that this treatment is difficult to apply in the case of nuclear accidents. Administration of radioprotectants before irradiation decreases damage to healthy cells, while not protecting cancerous tissues. In the future, stimulation of gastrointestinal and hemopoietic progenitor cells may be possible using cell growth regulators, but much remains to be done to improve the treatment of radiation damage to the gastrointestinal tract. 77 references.

  8. Prospects for management of gastrointestinal injury associated with the acute radiation syndrome

    SciTech Connect

    Dubois, A.; Walker, R.I.

    1988-08-01

    The effect of total-body ionizing radiation on the digestive tract is dose-dependent and time-dependent. At low doses (1.5 Gy), one observes only a short prodromal syndrome consisting of nausea, vomiting, and gastric suppression. At doses>6 Gy, the prodromal syndrome is more marked, and it is followed after a 2-5-day remission period by a subacute syndrome, characterized by diarrhea and hematochezia. This gastrointestinal syndrome is superimposed onto a radiation-induced bone marrow suppression. The combination of intestinal and hemopoietic syndromes results in dehydration, anemia, and infection, leading eventually to irreversible shock and death. The treatment of prodromal symptoms is based on the administration of antiemetics and gastrokinetics, although an effective treatment devoid of side effects is not yet available for human therapy. The treatment of the gastrointestinal subacute syndrome remains difficult and unsuccessful after exposure to total-body doses >8-10 Gy. Supportive therapy to prevent infection and dehydration may be effective if restoration or repopulation of the intestinal and bone marrow stem cells does occur. In addition, bone marrow transplantation may improve the prospect of treating the hemopoietic syndrome, although the experience gained in Chernobyl suggests that this treatment is difficult to apply in the case of nuclear accidents. Administration of radioprotectants before irradiation decreases damage to healthy cells, while not protecting cancerous tissues. In the future, stimulation of gastrointestinal and hemopoietic progenitor cells may be possible using cell growth regulators, but much remains to be done to improve the treatment of radiation damage to the gastrointestinal tract.

  9. The extent, time course, and fraction size dependence of mouse spinal cord recovery from radiation injury

    SciTech Connect

    Lavey, R.S.; Taylor, M.G.; Tward, J.D.

    1994-10-15

    This experiment was designed to assess: (a) the influence of fraction size and time interval between fractions on the tolerance of the spinal cord to high cumulative doses of radiation; and (b) the influence of the long-term recovery process on the tolerance of the spinal cord to reirradiation. The T10-L2 level of the spinal cord of C3Hf mice was irradiated using a conventionally fractionated regimen of 2.0 Gy once daily, a prolonged fractionated regimen of 1.2 Gy once daily, a hyperfractionated regimen of 1.2 Gy twice daily, or a single dose of 12 Gy followed 0-190 days later by a second dose of 5-20 Gy. Mice in the multifractionated regimen groups were given a single 15 Gy top-up- dose 24 h after reaching a cumulative fractionated dose of 24-70 Gy. Hind limb strength was measured weekly for 2 years after the completion of irradiation. Paralysis occurred in a bimodal time distribution, with peaks at 5-10 months and 15-23 months after the completion of irradiation. The cumulative radiation dose was directly associated with the incidence of paralysis in each radiation schedule (p<0.0001) and inversely associated with the time to onset of paralysis in the 1.2 Gy b.i.d. (p = 0.0001) and 2.0 Gy q.d. schedules (p = 0.03). The median latency of paralysis in each group was inversely associated with the incidence of paralysis in that group (p =<0.001). Decreasing the fraction size from 2.0 to 1.2 Gy once daily markedly increased the radiation tolerance of the spinal cord (p <0.0001), consistent with a very small alpha-beta value of -0.30 Gy ({approximately}95% confidence interval -0.72, +0.18) in the linear-quadratic model. Decreasing the time interval from 24 h to alternating 8 and 16 h periods produced an offsetting diminuation in cord tolerance (p <0.0001). 36 refs., 5 figs., 6 tabs.

  10. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

    PubMed

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

    2016-08-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  11. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs

    PubMed Central

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M.; Ding, Bi-Sen

    2016-01-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  12. Modification of radiation-induced brain injury by alpha-difluoromethylornithine.

    PubMed

    Gobbel, G T; Marton, L J; Lamborn, K; Seilhan, T M; Fike, J R

    1991-12-01

    The effect of alpha-difluoromethylornithine (DFMO) on 125I-induced brain injury was investigated in a dog model. Cerebrospinal putrescine levels were reduced from baseline levels 1-2 weeks after irradiation in animals treated with 125I and DFMO, while putrescine levels were elevated in 125I and saline-treated animals. In addition, the time course of changes in the volumes of edema, necrosis, and tissue showing evidence of blood-brain barrier breakdown was altered significantly by DFMO treatment. The most significant alterations occurred 2-4 weeks after irradiation, at which times the average volumes of damage in DFMO-treated animals were reduced compared to saline-treated animals. The time course of alterations in blood-to-brain transfer, brain-to-blood transfer, and vascularity following irradiation was also altered by DFMO treatment. Analysis of variance demonstrated a strong relationship of blood-to-brain transfer and vascularity to volume of edema, suggesting that the effect of DFMO on edema may be partially mediated by its effects on blood-brain barrier breakdown.

  13. Prenatal and neonatal radiation injury and lymphohematopoietic development in the dog

    SciTech Connect

    Nold, J.B.

    1985-01-01

    Immunologic and hematopoietic responses were studied in beagle dogs following prenatal or neonatal irradiation to evaluate the effects of ionizing radiation on the developing lymphohematopoietic system. In prenatally-irradiated dogs thymic medullary volumes were significantly reduced at birth, but had returned to control levels by 12 weeks of age. Irradiated dogs exhibited a significant reduction in primary humoral antibody responses and showed a concurrent decrease in T helper lymphocytes in the peripheral blood. In neonatally-irradiated dogs lymphocyte blastogenic responses were sharply decreased at 8 weeks, but returned to control levels by 12 weeks of age. Contact sensitivity to dinitrochlorobenzene was decreased, indicating reduced cell-mediated immune responses. Alterations in peripheral blood lymphocyte subpopulations included decreases in B cells and increases in T cells, possibly due to increased numbers of T suppressor cells. There were significant reductions in body size and body tissue weights in all irradiated dogs, although these were more severe and persistent in the prenatally-irradiated dogs. These data show that prenatally or neonatally-irradiated dogs have significantly postnatal immunologic and hematopoietic defects. The effect on bone marrow function in prenatally-irradiated dogs was more severe and persistent than in neonatally-irradiated animals; however, the neonatally-irradiated dogs exhibited more severe alterations in lymphocyte subpopulations than did the prenatally-irradiated dogs. The observation of altered lymphocyte subpopulations suggests altered immunoregulation and raises some important questions relating to radiation-induced immunodeficiency and increased susceptibility to clinical disease, including neoplasia.

  14. Zinc administration modulates radiation-induced oxidative injury in lens of rat

    PubMed Central

    Taysi, Seyithan; Okumus, Seydi; Akyuz, Mehmet; Uzun, Naim; Aksoy, Adnan; Demir, Elif; Orkmez, Mustafa; Tarakcioglu, Mehmet; Adli, Mustafa

    2012-01-01

    Background: The aim of this study was to evaluate the antioxidant role of zinc (Zn) against radiation-induced cataract in the rat lens after total cranial irradiation with a single 5 Gray (Gy) dose of gamma irradiation. Materials and Methods: Twenty-one Sprague-Dawley rats were used for the experiment. The control group did not receive Zn or irradiation but received 1-ml saline orally plus sham-irradiation. The irradiation (IR) group received 5 Gy gamma irradiation to the total cranium as a single dose plus 0.1 ml physiological saline intraperitoneally. The IR plus Zn group received irradiation to total cranium plus 10 mg/kg/day Zn intraperitoneally. Biochemical parameters measured in rat lenses were carried out using spectrophotometric techniques. Results: Lens total (enzymatic plus non-enzymatic) superoxide scavenger activity (TSSA), glutathione reductase (GRD), and glutathione-S-transferase (GST) activities significantly increased in the IR plus Zn groups when compared with the IR group. However, TSSA, GRD and GST activities were significantly lower in the IR group when compared with the control group. Lens non-enzymatic superoxide scavenger activity (NSSA) in the IR plus Zn group was significantly increased compared to that of the IR group. Lens xanthine oxidase (XO) activity in the IR group significantly increased compared to that of both the control and IR plus Zn groups. Conclusion: Zn has clear antioxidant properties and prevented oxidative stress by scavenging free radicals generated by ionizing radiation in rat lenses. PMID:24082625

  15. Action spectrum and mechanisms of UV radiation-induced injury in lupus erythematosus

    SciTech Connect

    Kochevar, I.E.

    1985-07-01

    Photosensitivity associated with lupus erythematosus (LE) is well established. The photobiologic basis for this abnormal response to ultraviolet radiation, however, has not been determined. This paper summarizes the criteria for elucidating possible photobiologic mechanisms and reviews the literature relevant to the mechanism of photosensitivity in LE. In patients with LE, photosensitivity to wavelengths shorter than 320 nm has been demonstrated; wavelengths longer than 320 nm have not been adequately evaluated. DNA is a possible chromophore for photosensitivity below 320 nm. UV irradiation of skin produces thymine photodimers in DNA. UV-irradiated DNA is more antigenic than native DNA and the antigenicity of UV-irradiated DNA has been proposed, but not proven, to be involved in the development of clinical lesions. UV irradiation of mice previously injected with anti-UV-DNA antibodies produces Ig deposition and complement fixation that appears to be similar to the changes seen in lupus lesions. Antibodies to UV-irradiated DNA occur in the serum of LE patients although a correlation between antibody titers and photosensitivity was not observed. Defective repair of UV-induced DNA damage does not appear to be a mechanism for the photosensitivity in LE. Other mechanisms must also be considered. The chromophore for photosensitivity induced by wavelengths longer than 320 nm has not been investigated in vivo. In vitro studies indicate that 360-400 nm radiation activates a photosensitizing compound in the lymphocytes and serum of LE patients and causes chromosomal aberrations and cell death. The mechanism appears to involve superoxide anion.

  16. Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging.

    PubMed

    Wang, Silun; Qiu, Deqiang; So, Kwok-Fai; Wu, Ed X; Leung, Lucullus H T; Gu, Jing; Khong, Pek-Lan

    2013-03-01

    We aim to study radiation induced white matter injury in a pre-clinical model using Diffusion tensor MR imaging (DTI). Nineteen 12-week old Sprague-Dawley rats were irradiated to the right hemisphere using a linear accelerator. The dose distribution map was coregistered to the DTI map to generate the actual radiation dose to each white matter tract. Rats underwent longitudinal DTI scans at five time points from 4 to 48 weeks post-radiation with histological evaluations. Fractional anisotropy (FA) of the external capsule, fornix, cerebral peduncle, anterior commissure, optic tract and optic nerve was evaluated. Radiation dose was highest at the ipsilateral external capsule and fornix (29.4 ± 1.3 and 29.8 ± 1.1 Gy, respectively). Optic nerve received 50 % dose to the external capsule and other white matter tracts received 80 % dose. Significantly lower FA was firstly found in the ipsilateral external capsule at 4 weeks post-radiation and in the ipsilateral fornix at 40 weeks post-radiation compared to the contralateral side. Significantly lower FA was found in contralateral optic nerve compared to ipsilateral optic nerve at 48 weeks post-radiation despite ipsilateral optic nerves receiving higher radiation dose than contralateral optic nerve (p = 0.021). No differences were found in other white matter regions until 48 weeks. Histology indicated demyelination, axonal degeneration and coagulative necrosis in all injured white matter. DTI can serve as a promising tool for assessment of radiation induced white matter injury and regional radiosensitivity of white matter tracts. PMID:23334608

  17. The use of isodose levels to interpret radiation induced lung injury: a quantitative analysis of computed tomography changes

    PubMed Central

    Knoll, Miriam A.; Sheu, Ren Dih; Knoll, Abraham D.; Kerns, Sarah L.; Lo, Yeh-Chi; Rosenzweig, Kenneth E.

    2016-01-01

    Background Patients treated with stereotactic body radiation therapy (SBRT) for lung cancer are often found to have radiation-induced lung injury (RILI) surrounding the treated tumor. We investigated whether treatment isodose levels could predict RILI. Methods Thirty-seven lung lesions in 32 patients were treated with SBRT and received post-treatment follow up (FU) computed tomography (CT). Each CT was fused with the original simulation CT and treatment isodose levels were overlaid. The RILI surrounding the treated lesion was contoured. The RILI extension index [fibrosis extension index (FEI)] was defined as the volume of RILI extending outside a given isodose level relative to the total volume of RILI and was expressed as a percentage. Results Univariate analysis revealed that the planning target volume (PTV) was positively correlated with RILI volume at FU: correlation coefficient (CC) =0.628 and P<0.0001 at 1st FU; CE =0.401 and P=0.021 at 2nd FU; CE =0.265 and P=0.306 at 3rd FU. FEI −40 Gy at 1st FU was significantly positively correlated with FEI −40 Gy at subsequent FU’s (CC =0.689 and P=6.5×10−5 comparing 1st and 2nd FU; 0.901 and P=0.020 comparing 2nd and 3rd FU. Ninety-six percent of the RILI was found within the 20 Gy isodose line. Sixty-five percent of patients were found to have a decrease in RILI on the second 2nd CT. Conclusions We have shown that RILI evolves over time and 1st CT correlates well with subsequent CTs. Ninety-six percent of the RILI can be found to occur within the 20 Gy isodose lines, which may prove beneficial to radiologists attempting to distinguish recurrence vs. RILI. PMID:26981453

  18. Bioactive compounds in green tea leaves attenuate the injury of retinal ganglion RGC-5 cells induced by H2O2 and ultraviolet radiation.

    PubMed

    Jin, Jianchang; Ying, Hao; Huang, Meirong; Du, Qizhen

    2015-11-01

    The Chinese commonly believe that tea helps maintain clear vision. This viewpoint has been recorded in Chinese medical books also. The key bioactive compounds in green tea leaves, (-)-epigallocatechin gallate (EGCG), L-theanine (theanine) and caffeine, were investigated for their abilities to attenuate the injury of retinal ganglion cells (RGC-5) induced by H2O2 and ultraviolet radiation. Theanine and caffeine promoted cell growth while concentrations of EGCG greater than 10μg/ml inhibited cell growth. The nine and caffeine both protected RGC-5 cells from injury as well as enhanced their recovery, while EGCG only protected the cells from injury and did not help them to recover. Tea is a unique drink, which is simultaneously enriched with EGCG, theanine and caffeine. The role of these compounds in optic nerve protection may partially explain why some tea drinkers feel enhanced vision. PMID:26687755

  19. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    SciTech Connect

    Ali, Haytham; Galal, Omima; Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan; Abdelrahim, Eman; Ono, Yusuke; Mostafa, Emtethal; Li, Tao-Sheng

    2014-09-26

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

  20. Pathophysiology of combined radiation injuries: A review and analysis of the literature on non-human research. Technical report, 28 Sep 88-1 Jan 90

    SciTech Connect

    Baum, S.J.

    1991-07-01

    One hundred and seventy one references applicable to determining the effect of tactical nuclear weapons on military personnel have been reviewed, and the significant conclusions are reported. The study reviews the scientific literature and focuses on animal experiments published from 1933 to the present time, including a number of German studies and some Soviet research not previously reviewed in English language publications. Recurring themes of the review are the synergistic increase in mortality when injury (burn, wound, bleeding, fracture, etc.) follows irradiation and the reduction in mortality when injury precedes irradiation and/or when antibiotics are administered. The synergistic increases are attributed to radiation damage to the bone marrow precursor cells, which reduces the protective mechanisms (leukopenia) and permits easier onset of bacteremia and septicemia. Radiation, in addition to favoring infection, is also found to prolong and complicate the normal healing processes. The addition of burns or wounds shortens the latent period and results in earlier onset of the manifest illness phase.

  1. Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury

    SciTech Connect

    Wesselius, L.J.; Floreani, A.A.; Kimler, B.F.; Papasian, C.J.; Dixon, A.Y. )

    1989-11-01

    The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

  2. Synchrotron Radiation X-Ray Phase-Contrast Tomography Visualizes Microvasculature Changes in Mice Brains after Ischemic Injury

    PubMed Central

    Ji, Yuanyuan; Xie, Bohua; Lin, Xiaojie

    2016-01-01

    Imaging brain microvasculature is important in plasticity studies of cerebrovascular diseases. Applying contrast agents, traditional μCT and μMRI methods gain imaging contrast for vasculature. The aim of this study is to develop a synchrotron radiation X-ray inline phase-contrast tomography (SRXPCT) method for imaging the intact mouse brain (micro)vasculature in high resolution (~3.7 μm) without contrast agent. A specific preparation protocol was proposed to enhance the phase contrast of brain vasculature by using density difference over gas-tissue interface. The CT imaging system was developed and optimized to obtain 3D brain vasculature of adult male C57BL/6 mice. The SRXPCT method was further applied to investigate the microvasculature changes in mouse brains (n = 14) after 14-day reperfusion from transient middle cerebral artery occlusion (tMCAO). 3D reconstructions of brain microvasculature demonstrated that the branching radius ratio (post- to preinjury) of small vessels (radius < 7.4 μm) in the injury group was significantly smaller than that in the sham group (p < 0.05). This result revealed the active angiogenesis in the recovery brain after stroke. As a high-resolution and contrast-agent-free method, the SRXPCT method demonstrates higher potential in investigations of functional plasticity in cerebrovascular diseases. PMID:27563468

  3. Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy

    SciTech Connect

    Fox, Matthew S.; Ouriadov, Alexei; Hegarty, Elaine; Thind, Kundan; Wong, Eugene; Hope, Andrew; Santyr, Giles E.

    2014-07-15

    Purpose: Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized{sup 129}Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points). Methods: In this study, dynamic{sup 129}Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (T{sub Tr-tissue} and T{sub Tr-RBC}) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a {sup 60}Co source. A separate group of six healthy age-matched rats served as a control group. Results: T{sub Tr-tissue} values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p < 0.05) with respect to the healthy control group (37.2 ± 4.8 ms). T{sub Tr-RBC} did not show any significant changes between groups. T{sub Tr-tissue} was strongly correlated with T{sub Tr-RBC} in the control group (r = 0.9601 p < 0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p < 0.05) in the two-week group (54.2 ± 12.3 mm Hg) compared to those from a representative control group (85.0 ± 10.0 mm Hg). Histology of a separate group of similarly irradiated animals confirmed the presence of inflammation due to radiation exposure with alveolar wall thicknesses that were significantly different (p < 0.05). At six weeks post

  4. Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung

    SciTech Connect

    Siva, Shankar; Hardcastle, Nicholas; Kron, Tomas; Bressel, Mathias; Callahan, Jason; MacManus, Michael P.; Shaw, Mark; Plumridge, Nikki; Hicks, Rodney J.; Steinfort, Daniel; Ball, David L.; Hofman, Michael S.

    2015-10-01

    Purpose: To investigate {sup 68}Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r{sup 2}=0.99, P<.01), with ventilation strongly negatively linear (r{sup 2}=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET

  5. SU-E-J-247: Time Evolution of Radiation-Induced Lung Injury After Stereotactic Proton Therapy

    SciTech Connect

    Grassberger, C; Sharp, G; Fintelmann, F; Paganetti, H; Willers, H

    2015-06-15

    Purpose: Quantitative metrics to assess patient-specific radiation-induced lung injury have the potential to guide individualization of therapy and be early indicators of recurrence. Here we investigate computed tomography (CT) density changes in normal lung after stereotactic Proton Therapy. Methods: Participants in a phase-I clinical trial for stereotactic body radiation therapy (SBRT) with protons are analyzed on a rolling basis. The dataset includes 9 patients with 34 CT images to date. Follow-up images are registered to the planning CT using deformable image registration and the change in CT density is correlated to the dose to examine the time-evolution of Hounsfield Unit (HU) changes after large doses of proton radiation. Results: The lung density observed on the follow-up images increases significantly with dose for all dose levels above 5 Gy(RBE) (p<0.001) for 8/9 patients. The change per unit dose [HU/Gy] varies significantly among the patients, from 0.1 (for the one patient without significant correlation) to 5.7 ΔHU/Gy(RBE). The current population average of ΔHU/Gy(RBE) is 2.1, i.e. a 1 Gy(RBE) increase in dose leads on average to a 2.1 HU increase in CT density. The slope of the dose-response curve is constant for all timepoints investigated (from 3–24+ months). Additionally a pronounced non-linearity in the dose response curve is noted for long follow-up times (>18 months). Conclusion: CT density changes have a robust correlation with proton dose, quantitatively similar to photon dose, and may allow estimation of a patient’s intrinsic radiosensitivity after proton therapy. The stability of the correlation with time however diverges from what is known about CT response after photon irradiation. This could have important implications for clinical decision-making during proton therapy for lung cancer, especially for scheduling of follow-up CT/PET imaging and diagnosis of recurrence.

  6. Transplantation of BMSCs expressing hVEGF165 /hBD3 promotes wound healing in rats with combined radiation-wound injury.

    PubMed

    Xia, Zhangquan; Zhang, Congji; Zeng, Yi; Wang, Tao; Ai, Guoping

    2014-06-01

    The combined radiation-wound injury is a refractory wound with decreased number or dysfunction of repairing cells and growth factors. This remains a challenge in clinical practice. The object of this study is to evaluate the therapeutic efficacy of a combination of human vascular endothelial growth factor 165 (hVEGF(165)) and human beta-defensin 3 (hBD3) in the treatment of such wounds. A plasmid-carrying hVEGF(165) gene and hBD3 gene was used to transfect rat bone-marrow-derived mesenchymal stem cells (BMSCs). The supernatant from the modified BMSCs significantly promoted the proliferation and cell migration of human endothelial cells and it also inhibited the growth of bacteria and fungus, demonstrating the successful expression of the transfected genes. The hVEGF(165)/hBD3-modified BMSCs were then injected into the sites of combined radiation-wound injury on rats. It demonstrated that wound-healing time was shortened significantly in the treated rats. The granulation tissue formation/maturation, skin appendage regeneration and collagen deposition were also improved significantly. Strong expression of hVEGF(165) and hBD3 was detected in the wound surface at early stage of the healing. The results indicate that topical transplantation of hVEGF(165)/hBD3-modified BMSCs promoted wound healing, and this gene therapy strategy presents a promising approach in the treatment of refractory wounds such as the combined radiation-wound injury.

  7. Radiation injury in the human kidney: A prospective analysis using specific scintigraphic and biochemical endpoints

    SciTech Connect

    Dewit, L.; Anninga, J.K.; Hoefnagel, C.A.; Nooijen, W.J. )

    1990-10-01

    Renal function was prospectively analyzed in 26 evaluable patients, irradiated to various doses on their kidneys for neoplastic disease. Glomerular function was assessed by 99mTc-DTPA renography, creatinine clearance, and serum beta 2-microglobulin, whereas tubular function was monitored by 99mTc-DMSA scintigraphy, urine beta 2-microglobulin, urine N-acetyl glucosaminidase, and alanine aminopeptidase and a urine concentration test. In the patients given the highest irradiation dose to the entire left kidney, that is, 40 Gy in 5 1/2 weeks, glomerular and tubular functional impairment, as assessed scintigraphically, progressed at a rate of 2.0 +/- 1.0% (+/- 1 SD) and 2.0 +/- 0.5% per month, respectively, down to 30-40% after 3 to 5 years. The overall glomerular function, as assessed by creatinine clearance, decreased by only 20%. In the patients irradiated unilaterally on the upper pole to 40 Gy in 4 weeks, glomerular and tubular function in the left kidney deteriorated at 0.75 +/- 0.33% and 0.75 +/- 0.20% per month in the first 2 years, down to 75-80% at 5 years. This smaller reduction was due to shielding of a part of the left kidney. No changes were observed, thus far, after bilateral whole kidney irradiation to 17-18 Gy in 3 1/2 weeks. The concentration capacity of the kidney after total volume irradiation was not impaired. There was a trend for an increase in diastolic blood pressure in 3 out of 5 patients given the high dose irradiation to the entire left kidney and in 2 out of 7 patients irradiated on the upper pole of the left kidney. The progressive nature of the radiation nephropathy stresses the need for long term follow-up to determine more accurately the tolerance dose of the human kidney for irradiation.

  8. Dose Optimization Study of AEOL 10150 as a Mitigator of Radiation-Induced Lung Injury in CBA/J Mice

    PubMed Central

    Murigi, Francis N.; Mohindra, Pranshu; Hung, Chiwei; Salimi, Shabnam; Goetz, Wilfried; Pavlovic, Radmila; Jackson, Isabel L.; Vujaskovic, Zeljko

    2015-01-01

    AEOL 10150 is a catalytic metalloporphyrin superoxide dismutase mimic being developed as a medical countermeasure for radiation-induced lung injury (RILI). The efficacy of AEOL 10150 against RILI through a reduction of oxidative stress, hypoxia and pro-apoptotic signals has been previously reported. The goal of this study was to determine the most effective dose of AEOL 10150 (daily subcutaneous injections, day 1–28) in improving 180-day survival in CBA/J mice after whole-thorax lung irradiation (WTLI) to a dose of 14.6 Gy. Functional and histopathological assessments were performed as secondary end points. Estimated 180-day survival improved from 10% in WTLI alone to 40% with WTLI-AEOL 10150 at 25 mg/kg (P = 0.065) and to 30% at 40 mg/kg (P = 0.023). No significant improvement was seen at doses of 5 and 10 mg/kg or at doses between 25 and 40 mg/kg. AEOL 10150 treatment at 25 mg/kg lowered the respiratory function parameter of enhanced pause (Penh) significantly, especially at week 16 and 18 (P = 0.044 and P = 0.025, respectively) compared to vehicle and other doses. Pulmonary edema/congestion were also significantly reduced at the time of necropsy among mice treated with 25 and 40 mg/kg AEOL 10150 compared to WTLI alone (P < 0.02). In conclusion, treatment with AEOL 10150 at a dose of 25 mg/kg/day for a total of 28 days starting 24 h after WTLI in CBA/J mice was found to be the optimal dose with improvement in survival and lung function. Future studies will be required to determine the optimal duration and therapeutic window for drug delivery at this dose. PMID:26414508

  9. Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs

    PubMed Central

    YUE, HAIYING; HU, KAI; LIU, WENQI; JIANG, JIE; CHEN, YUHUA; WANG, RENSHENG

    2015-01-01

    Radiation-induced lung injury (RILI) is a common complication associated with thoracic radiotherapy. The aim of the present study was to investigate the effects of a single 15-Gy dose of right-thoracic lung irradiation on the expression levels of matrix metalloproteinases (MMPs) and other proteins in the alveolar epithelial type II (AE2) cells of Bama minipigs. All minipigs received either right-thoracic irradiation or sham irradiation under anesthesia, and were sacrificed at 4, 8, 12 or 24 weeks after irradiation. Collagen deposition was measured using Massons trichrome staining. Surfactant protein A (SP-A), transforming growth factor β1 (TGFβ1), MMP2, MMP9, vimentin and E-cadherin protein expression levels were evaluated using western blot analysis, and the MMP2 and MMP9 gelatinase activities were tested using gelatin zymography. SP-A and α-smooth muscle actin (α-SMA) co-localization was visualized using double immunofluorescence staining. At each time-point following irradiation, a significant increase in TGFβ1, α-SMA, MMP2, MMP9 and vimentin protein expression levels and MMP2 and MMP9 gelatinase activity were observed in the irradiated lungs compared with the sham-irradiated controls. By contrast, SP-A and E-cadherin protein expression levels decreased in a time-dependent manner post-irradiation. SP-A and α-SMA co-localization was observed in irradiated alveolar epithelial cells. These data demonstrate that E-cadherin, SP-A, MMP2 and MMP9 may function as sensitive predictors of RILI. Epithelial-mesenchymal transition (EMT) occurs in the irradiated lungs of Bama minipigs, and MMP2 and MMP9 may contribute to EMT in AE2 cells by regulating TGFβ1. Therefore, EMT may serve a crucial function in the development of RILI. PMID:26622503

  10. [Delayed puberty].

    PubMed

    Antoniazzi, F; Zamboni, G; Tatò, L

    1996-01-01

    Delayed puberty can be defined as the absence of any signs of puberty in subjects that have attained an age at the upper limit (+2DS) for the onset of puberty, that means 13 years in girls and 14 years in boys. The causes of delayed puberty can be classified into three groups, functional temporary impairment in gonadotropin and sex steroid secretion (most frequently constitutional delay of puberty), hypothalamo-pituitary failure with deficiency in gonadotropin secretion, primary gonadal failure with increased gonadotropin levels. The Authors discuss about etiology, diagnostic testing and therapeutic approach in these conditions. The majority of children with delayed puberty are males that have only a constitutional delay of growth and puberty. It is difficult, in teenage years, to distinguish this common and benign condition from true gonadotropin deficiency, in spite of the variety of endocrine tests developed for this purpose. Individuals with constitutional delayed puberty with a bone age greater than 11.5 years, show after triptorelin stimulation an increase in LH capable of distinguishing them from patients with gonadotropin deficiency. In our opinion this could be an important screening test to exclude gonadotropin deficiency in boys with delayed puberty.

  11. Experimental traumatic brain injury

    PubMed Central

    2010-01-01

    Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury. PMID:20707892

  12. Caffeic acid phenethyl ester attenuates ionize radiation-induced intestinal injury through modulation of oxidative stress, apoptosis and p38MAPK in rats.

    PubMed

    Jin, Liu-Gen; Chu, Jian-Jun; Pang, Qing-Feng; Zhang, Fu-Zheng; Wu, Gang; Zhou, Le-Yuan; Zhang, Xiao-Jun; Xing, Chun-Gen

    2015-07-01

    Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. This study aimed to investigate the radioprotective effects of CAPE on X-ray irradiation induced intestinal injury in rats. Rats were intragastrically administered with 10 μmol/kg/d CAPE for 7 consecutive days before exposing them to a single dose of X-ray irradiation (9Gy) to abdomen. Rats were sacrificed 72 h after exposure to radiation. We found that pretreatment with CAPE effectively attenuated intestinal pathology changes, apoptosis, oxidative stress, bacterial translocation, the content of nitric oxide and myeloperoxidase as well as the concentration of plasma tumor necrosis factor-α. Pretreatment with CAPE also reversed the activation of p38MAPK and the increased expression of intercellular cell adhesion molecule-1 induced by radiation in intestinal mucosa. Taken together, these results suggest that pretreatment with CAPE could be a promising candidate for treating radiation-induced intestinal injury. PMID:26122083

  13. Contingencies promote delay tolerance.

    PubMed

    Ghaemmaghami, Mahshid; Hanley, Gregory P; Jessel, Joshua

    2016-09-01

    The effectiveness of functional communication training as treatment for problem behavior depends on the extent to which treatment can be extended to typical environments that include unavoidable and unpredictable reinforcement delays. Time-based progressive delay (TBPD) often results in the loss of acquired communication responses and the resurgence of problem behavior, whereas contingency-based progressive delay (CBPD) appears to be effective for increasing tolerance for delayed reinforcement. No direct comparison of TBPD and CBPD has, however, been conducted. We used single-subject designs to compare the relative efficacy of TBPD and CBPD. Four individuals who engaged in problem behavior (e.g., aggression, vocal and motor disruptions, self-injury) participated. Results were consistent across all participants, and showed lower rates of problem behavior and collateral responses during CBPD than during TBPD. The generality of CBPD treatment effects, including optimal rates of communication and compliance with demands, was demonstrated across a small but heterogeneous group of participants, reinforcement contingencies, and contexts. PMID:27449401

  14. Delayed traumatic intracerebral haemorrhage

    PubMed Central

    Baratham, Gopal; Dennyson, William G.

    1972-01-01

    Twenty-one out of 7,866 head injuries were complicated by the development of delayed intracerebral haematomata. The age distribution of patients with this condition closely resembled that of patients with subdural haematomata and differed sharply from patients with extradural haemorrhage. This finding, combined with the fact that the two conditions often coexisted, suggests the possibility of similar aetiological factors operating in their production. The injury producing the lesion was often minor and the larger haematomata appeared to be associated with longer `asymptomatic' intervals. The neurological deterioration was in most instances clearly the result of an increase in intracranial pressure. When possible, angiography followed by definitive craniotomy was the most satisfactory method of management and multiple burr holes even when combined with needling of the hemisphere yielded unsatisfactory results. The distribution of lesions tended to confirm their traumatic origin. On no occasion was there a vascular abnormality to account for the haemorrhage and, despite the fact that the ages of most patients were in the seventh and eighth decades, the incidence of degenerative vascular disease was small. Contusional injury causes a local failure of the mechanisms that regulate cerebral blood flow. Hypoxia, hypercapnia, and venous congestion produce cerebral hyperaemia which encourages gradual haematoma formation particularly at the sites of injury. This explains not only the situation of the lesions but also the latency between the trauma and their development. PMID:5084138

  15. Subtoxic N-methyl-D-aspartate delayed neuronal death in ischemic brain injury through TrkB receptor- and calmodulin-mediated PI-3K/Akt pathway activation.

    PubMed

    Xu, Jing; Zhang, Quan-Guang; Li, Chong; Zhang, Guang-Yi

    2007-01-01

    Previous studies have shown that subtoxic NMDA moderated the neuronal survival in vitro and vivo. We performed this experiment to clarify the precise mechanism underlie subtoxic NMDA delayed neuronal death in ischemic brain injury. We found that pretreatment of NMDA (100 mg/kg) increased the number of the surviving CA1 pyramidal cells of hippocampus at 5 days of reperfusion. This dose of NMDA could also enhance Akt activation after ischemia/reperfusion (I/R). Here, we examined the possible mechanism that NMDA induced Akt activation. On the one hand, we found NMDA receptor-mediated Akt activation was associated with increased expression of BDNF (brain-derived neurotrophic factor) and activation of its high-affinity receptor TrkB after I/R in the hippocampus CA1 region, which could be held down by TrkB receptor antagonist K252a. On the other hand, we found that NMDA enhanced the binding of Ca2+-dependent calmodulin (CaM) to p85 (the regulation subunit of PI-3K), which led to the activation of Akt. W-13, an active CaM inhibitor, prevented the combination of CaM and p85 and subsequent Akt activation. Furthermore, NMDA receptor-mediated Akt activation was reversed by combined treatment with LY294002, the specific blockade of PI-3K. Taken together, our results suggested that subtoxic NMDA exerts the neuroprotective effect via activation of prosurvival PI-3K/Akt pathway against ischemic brain injury, and BDNF-TrkB signaling and Ca2+-dependent CaM cascade might contribute to NMDA induced activation of PI-3K/Akt pathway.

  16. Detecting Radiation-Induced Injury Using Rapid 3D Variogram Analysis of CT Images of Rat Lungs

    SciTech Connect

    Jacob, Rick E.; Murphy, Mark K.; Creim, Jeffrey A.; Carson, James P.

    2013-10-01

    A new heterogeneity analysis approach to discern radiation-induced lung damage was tested on CT images of irradiated rats. The method, combining octree decomposition with variogram analysis, demonstrated a significant correlation with radiation exposure levels, whereas conventional measurements and pulmonary function tests did not. The results suggest the new approach may be highly sensitive for assessing even subtle radiation-induced changes

  17. CT appearance of radiation injury of the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) for lung cancers: Are patients with pulmonary emphysema also candidates for SBRT for lung cancers?

    SciTech Connect

    Kimura, Tomoki . E-mail: tkkimura@med.kawawa-u.ac.jp; Matsuura, Kanji; Murakami, Yuji; Hashimoto, Yasutoshi; Kenjo, Masahiro; Kaneyasu, Yuko; Wadasaki, Koichi; Hirokawa, Yutaka; Ito, Katsuhide; Okawa, Motoomi

    2006-10-01

    Purpose: The purpose of this study was to analyze the computed tomographic (CT) appearance of radiation injury to the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) and evaluate the difference by the presence of pulmonary emphysema (PE) for small lung cancers. Methods and Materials: In this analysis, 45 patients with 52 primary or metastatic lung cancers were enrolled. We evaluated the CT appearance of acute radiation pneumonitis (within 6 months) and radiation fibrosis (after 6 months) after SBRT. Clinical symptoms were evaluated by Common Terminology Criteria for Adverse Events, version 3.0. We also evaluated the relationship between CT appearance, clinical symptoms, and PE. Results: CT appearance of acute radiation pneumonitis was classified as follows: (1) diffuse consolidation, 38.5%; (2) patchy consolidation and ground-glass opacities (GGO), 15.4%; (3) diffuse GGO, 11.5%; (4) patchy GGO, 2.0%; (5) no evidence of increasing density, 32.6%. CT appearance of radiation fibrosis was classified as follows: (1) modified conventional pattern, 61.5%; (2) mass-like pattern, 17.3%; (3) scar-like pattern, 21.2%. Patients who were diagnosed with more than Grade 2 pneumonitis showed significantly less no evidence of increased density pattern and scar-like pattern than any other pattern (p = 0.0314, 0.0297, respectively). Significantly, most of these patients with no evidence of increased density pattern and scar-like pattern had PE (p = 0.00038, 0.00044, respectively). Conclusion: Computed tomographic appearance after SBRT was classified into five patterns of acute radiation pneumonitis and three patterns of radiation fibrosis. Our results suggest that SBRT can be also safely performed even in patients with PE.

  18. [Evaluation of the risk of delayed adverse effects of chronic combined exposure to radiation and chemical factors with the purpose to ensure safety in orbital and exploration space missions].

    PubMed

    Shafirkin, A V; Mukhamedieva, L N; Tatarkin, S V; Barantseva, M Iu

    2012-01-01

    The work had the aim to anatomize the existing issues with providing safety in extended orbital and exploration missions for ensuing estimation of actual values of the total radiation risk for the crew, and risks of other delayed effects of simultaneous exposure to ionizing radiation and chemical pollutants in cabin air, and a number of other stressful factors inevitable in space flight. The flow of chronic experiments for separate and combined studies with reproduction of air makeup and radiation doses in actual orbital and predicted exploration missions is outlined. To set safety limits, new approaches should be applied to the description of gradual norm degradation to pathologies in addition to several generalized quantitative indices of adaptation and straining of the regulatory systems, as well as of effectiveness of the compensatory body reserve against separate and combined exposure.

  19. [Evaluation of the risk of delayed adverse effects of chronic combined exposure to radiation and chemical factors with the purpose to ensure safety in orbital and exploration space missions].

    PubMed

    Shafirkin, A V; Mukhamedieva, L N; Tatarkin, S V; Barantseva, M Iu

    2012-01-01

    The work had the aim to anatomize the existing issues with providing safety in extended orbital and exploration missions for ensuing estimation of actual values of the total radiation risk for the crew, and risks of other delayed effects of simultaneous exposure to ionizing radiation and chemical pollutants in cabin air, and a number of other stressful factors inevitable in space flight. The flow of chronic experiments for separate and combined studies with reproduction of air makeup and radiation doses in actual orbital and predicted exploration missions is outlined. To set safety limits, new approaches should be applied to the description of gradual norm degradation to pathologies in addition to several generalized quantitative indices of adaptation and straining of the regulatory systems, as well as of effectiveness of the compensatory body reserve against separate and combined exposure. PMID:22624477

  20. Differential Expression of Homer1a in the Hippocampus and Cortex Likely Plays a Role in Radiation-Induced Brain Injury

    PubMed Central

    Moore, Elizabeth D.; Kooshki, Mitra; Wheeler, Kenneth T.; Metheny-Barlow, Linda J.; Robbins, Mike E.

    2014-01-01

    Fractionated partial or whole-brain irradiation is the primary treatment for metastatic brain tumors. Despite reducing tumor burden and increasing lifespan, progressive, irreversible cognitive impairment occurs in >50% of the patients who survive >6 months after fractionated whole-brain irradiation. The exact mechanism(s) responsible for this radiation-induced brain injury are unknown; however, preclinical studies suggest that radiation modulates the extracellular receptor kinase signaling pathway, which is associated with cognitive impairment in many neurological diseases. In the study reported here, we demonstrated that the extracellular receptor kinase transcriptionally-regulated early response gene, Homer1a, was up-regulated transiently in the hippocampus and down-regulated in the cortex of young adult male Fischer 344 X Brown Norway rats at 48 h after 40 Gy of fractionated whole-brain irradiation. Two months after fractionated whole-brain irradiation, these changes in Homer1a expression correlated with a down-regulation of the hippocampal glutamate receptor 1 and protein kinase Cγ, and an up-regulation of cortical glutamate receptor 1 and protein kinase Cγ. Two drugs that prevent radiation-induced cognitive impairment in rats, the angiotensin type-1 receptor blocker, L-158,809, and the angiotensin converting enzyme inhibitor, ramipril, reversed the fractionated whole-brain irradiation-induced Homer1a expression at 48 h in the hippocampus and cortex and restored glutamate receptor 1 and protein kinase Cγ to the levels in shamirradiated controls at 2 months after fractionated whole-brain irradiation. These data indicate that Homer1a is, (1) a brain region specific regulator of radiation-induced brain injury, including cognitive impairment and (2) potentially a druggable target for preventing it. PMID:24377717

  1. Iatrogenic Hepatopancreaticobiliary Injuries: A Review

    PubMed Central

    Vachhani, Prasanti G.; Copelan, Alexander; Remer, Erick M.; Kapoor, Baljendra

    2015-01-01

    Iatrogenic hepatopancreaticobiliary injuries occur after various types of surgical and nonsurgical procedures. Symptomatically, these injuries may lead to a variety of clinical presentations, including tachycardia and hypotension from hemobilia or hemorrhage. Iatrogenic injuries may be identified during the intervention, immediately afterwards, or have a delayed presentation. These injuries are categorized into nonvascular and vascular injuries. Nonvascular injuries include biliary injuries such as biliary leak or stricture, pancreatic injury, and the development of fluid collections such as abscesses. Vascular injuries include pseudoaneurysms, arteriovenous fistulas, dissection, and perforation. Imaging studies such as ultrasound, computed tomography, magnetic resonance imaging, and digital subtraction angiography are critical for proper diagnosis of these conditions. In this article, we describe the clinical and imaging presentations of these iatrogenic injuries and the armamentarium of minimally invasive procedures (percutaneous drainage catheter placement, balloon dilatation, stenting, and coil embolization) that are useful in their management. PMID:26038625

  2. Diagnostic criteria for cutaneous injuries in child abuse: classification, findings, and interpretation.

    PubMed

    Tsokos, Michael

    2015-06-01

    Physical abuse of children has many manifestations. Depending on the type of force involved, specific injury patterns are produced on the body of the child, the morphology and localization of which are forensically relevant in terms of diagnostic classification as child abuse. Typical patterned bruising includes, for example, tramline bruises resulting from blows with oblong, stick-like objects. In addition to rounded or one-sided horseshoe-shaped bite injuries, injuries of different ages, clustered injuries (e.g., three or more individual injuries in the same body region), and thermal injuries are typical results of abuse. Abusive scalds are usually characterized by a symmetrical impression and localization with sharp delineation of the scald wound edges, in contrast to accidental scalding injuries with radiating splash patterns ending in tapered points. The coloration of a hematoma can help indicate the time when the injury occurred. Lack of a coherent and comprehensible explanation for accidental injury constitutes grounds for suspecting abuse. Suspicions should be raised in cases of a delayed visit to a doctor, waiting for an unusually long period before summoning emergency medical help for serious injuries to a child, and when differing versions of a purported accident are provided. Documentation of the findings is highly relevant in later reviews of the diagnosis, for instance, when new relevant facts and investigative results come to light in subsequent criminal proceedings.

  3. Radiation

    NASA Video Gallery

    Outside the protective cocoon of Earth's atmosphere, the universe is full of harmful radiation. Astronauts who live and work in space are exposed not only to ultraviolet rays but also to space radi...

  4. Radiculopathy as Delayed Presentations of Retained Spinal Bullet

    PubMed Central

    Ryu, Bang; Choi, Man Kyu; Kim, Kee D

    2015-01-01

    Bullet injuries to the spine may cause injury to the anatomical structures with or without neurologic deterioration. Most bullet injuries are acute, resulting from direct injury. However, in rare cases, delayed injury may occur, resulting in claudication. We report a case of intradural bullet at the L3-4 level with radiculopathy in a 30-year-old male. After surgical removal, radicular and claudicating pain were improved significantly, and motor power of the right leg also improved. We report the case of intradural bullet, which resulted in delayed radiculopathy. PMID:26587197

  5. Delayed Axillary Artery Occlusion after Reverse Total Shoulder Arthroplasty

    PubMed Central

    Heitmiller, Richard F.

    2016-01-01

    Axillary artery injury has been associated with shoulder dislocation and surgery. We describe a case of delayed axillary artery occlusion after reverse total shoulder arthroplasty. The injury was confirmed by Doppler and angiography and was treated with angioplasty and stenting. Early recognition and treatment of this injury are mandatory for patients' recovery. PMID:27555975

  6. Traumatic Brain Injury and Dystonia

    MedlinePlus

    ... various neurological symptoms, often including dystonia and other movement disorders. Symptoms • Symptoms of a TBI can be mild, ... following an injury. Symptoms of dystonia and other movement disorders may be delayed by several months or years ...

  7. Radiation sickness

    MedlinePlus

    ... process so that they do not cause radiation injury to others. This may complicate the first aid and resuscitation process. Check the person's breathing and pulse. Start CPR , if necessary. Remove the person's clothing and place ...

  8. Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism

    SciTech Connect

    Wang Junru; Boerma, Marjan; Fu Qiang; Kulkarni, Ashwini; Fink, Louis M.; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2007-08-01

    Purpose: Microvascular injury plays a key role in normal tissue radiation responses. Statins, in addition to their lipid-lowering effects, have vasculoprotective properties that may counteract some effects of radiation on normal tissues. We examined whether administration of simvastatin ameliorates intestinal radiation injury, and whether the effect depends on protein C activation. Methods and Materials: Rats received localized, fractionated small bowel irradiation. The animals were fed either regular chow or chow containing simvastatin from 2 weeks before irradiation until termination of the experiment. Groups of rats were euthanized at 2 weeks and 26 weeks for assessment of early and delayed radiation injury by quantitative histology, morphometry, and quantitative immunohistochemistry. Dependency on protein C activation was examined in thrombomodulin (TM) mutant mice with deficient ability to activate protein C. Results: Simvastatin administration was associated with lower radiation injury scores (p < 0.0001), improved mucosal preservation (p = 0.0009), and reduced thickening of the intestinal wall and subserosa (p = 0.008 and p = 0.004), neutrophil infiltration (p = 0.04), and accumulation of collagen I (p = 0.0003). The effect of simvastatin was consistently more pronounced for delayed than for early injury. Surprisingly, simvastatin reduced intestinal radiation injury in TM mutant mice, indicating that the enteroprotective effect of simvastatin after localized irradiation is unrelated to protein C activation. Conclusions: Simvastatin ameliorates the intestinal radiation response. The radioprotective effect of simvastatin after localized small bowel irradiation does not appear to be related to protein C activation. Statins should undergo clinical testing as a strategy to minimize side effects of radiation on the intestine and other normal tissues.

  9. Cold injuries.

    PubMed

    Long, William B; Edlich, Richard F; Winters, Kathryne L; Britt, L D

    2005-01-01

    Exposure to cold can produce a variety of injuries that occur as a result of man's inability to adapt to cold. These injuries can be divided into localized injury to a body part, systemic hypothermia, or a combination of both. Body temperature may fall as a result of heat loss by radiation, evaporation, conduction, and convection. Hypothermia or systemic cold injury occurs when the core body temperature has decreased to 35 degrees C (95 degrees F) or less. The causes of hypothermia are either primary or secondary. Primary, or accidental, hypothermia occurs in healthy individuals inadequately clothed and exposed to severe cooling. In secondary hypothermia, another illness predisposes the individual to accidental hypothermia. Hypothermia affects multiple organs with symptoms of hypothermia that vary according to the severity of cold injury. The diagnosis of hypothermia is easy if the patient is a mountaineer who is stranded in cold weather. However, it may be more difficult in an elderly patient who has been exposed to a cold environment. In either case, the rectal temperature should be checked with a low-reading thermometer. The general principals of prehospital management are to (1) prevent further heat loss, (2) rewarm the body core temperature in advance of the shell, and (3) avoid precipitating ventricular fibrillation. There are two general techniques of rewarming--passive and active. The mechanisms of peripheral cold injury can be divided into phenomena that affect cells and extracellular fluids (direct effects) and those that disrupt the function of the organized tissue and the integrity of the circulation (indirect effects). Generally, no serious damage is seen until tissue freezing occurs. The mildest form of peripheral cold injury is frostnip. Chilblains represent a more severe form of cold injury than frostnip and occur after exposure to nonfreezing temperatures and damp conditions. Immersion (trench) foot, a disease of the sympathetic nerves and blood

  10. Cold injuries.

    PubMed

    Long, William B; Edlich, Richard F; Winters, Kathryne L; Britt, L D

    2005-01-01

    Exposure to cold can produce a variety of injuries that occur as a result of man's inability to adapt to cold. These injuries can be divided into localized injury to a body part, systemic hypothermia, or a combination of both. Body temperature may fall as a result of heat loss by radiation, evaporation, conduction, and convection. Hypothermia or systemic cold injury occurs when the core body temperature has decreased to 35 degrees C (95 degrees F) or less. The causes of hypothermia are either primary or secondary. Primary, or accidental, hypothermia occurs in healthy individuals inadequately clothed and exposed to severe cooling. In secondary hypothermia, another illness predisposes the individual to accidental hypothermia. Hypothermia affects multiple organs with symptoms of hypothermia that vary according to the severity of cold injury. The diagnosis of hypothermia is easy if the patient is a mountaineer who is stranded in cold weather. However, it may be more difficult in an elderly patient who has been exposed to a cold environment. In either case, the rectal temperature should be checked with a low-reading thermometer. The general principals of prehospital management are to (1) prevent further heat loss, (2) rewarm the body core temperature in advance of the shell, and (3) avoid precipitating ventricular fibrillation. There are two general techniques of rewarming--passive and active. The mechanisms of peripheral cold injury can be divided into phenomena that affect cells and extracellular fluids (direct effects) and those that disrupt the function of the organized tissue and the integrity of the circulation (indirect effects). Generally, no serious damage is seen until tissue freezing occurs. The mildest form of peripheral cold injury is frostnip. Chilblains represent a more severe form of cold injury than frostnip and occur after exposure to nonfreezing temperatures and damp conditions. Immersion (trench) foot, a disease of the sympathetic nerves and blood

  11. Lumbar corpectomy for correction of degenerative scoliosis from osteoradionecrosis reveals a delayed complication of lumbar myxopapillary ependymoma.

    PubMed

    Palejwala, Sheri K; Lawson, Kevin A; Kent, Sean L; Martirosyan, Nikolay L; Dumont, Travis M

    2016-08-01

    Osteoradionecrosis is a known complication following radiation therapy, presenting most commonly in the cervical spine as a delayed consequence of radiation that is often necessary in the management of head and neck cancers. In contrast, osteoradionecrosis has rarely been described in the lumbar spine. Here we describe, to our knowledge, the first reported case of lumbar spine osteoradionecrosis, after adjuvant radiation for a primary spinal cord tumor, leading to progressive degenerative scoliosis which required subsequent operative management. Established guidelines recommend that mature bone can tolerate a dose of up to 6000 cGy without injury. However, once bone has been exposed to radiation over this level progressive soft tissue changes may lead to devascularization, leaving the bone vulnerable to osteonecrosis, specifically when manipulated. Radiation necrosis can be progressive and lead to eventual mechanical instability requiring debridement and surgical fixation. In the setting of the lumbar spine, osseous necrosis can lead to biomechanical instability, deformity, pain, and neurologic deficit. PMID:27056674

  12. Protective effects of β-glucan against oxidative injury induced by 2.45-GHz electromagnetic radiation in the skin tissue of rats.

    PubMed

    Ceyhan, Ali Murat; Akkaya, Vahide Baysal; Güleçol, Şeyma Celik; Ceyhan, Betül Mermi; Özgüner, Fehmi; Chen, WenChieh

    2012-09-01

    In recent times, there is widespread use of 2.45-GHz irradiation-emitting devices in industrial, medical, military and domestic application. The aim of the present study was to investigate the effect of 2.45-GHz electromagnetic radiation (EMR) on the oxidant and antioxidant status of skin and to examine the possible protective effects of β-glucans against the oxidative injury. Thirty-two male Wistar albino rats were randomly divided into four equal groups: control; sham exposed; EMR; and EMR + β-glucan. A 2.45-GHz EMR emitted device from the experimental exposure was applied to the EMR group and EMR + β-glucan group for 60 min daily, respectively, for 4 weeks. β-glucan was administered via gavage at a dose of 50 mg/kg/day before each exposure to radiation in the treatment group. The activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the concentration of malondialdehyde (MDA) were measured in tissue homogenates of the skin. Exposure to 2.45-GHz EMR caused a significant increase in MDA levels and CAT activity, while the activities of SOD and GSH-Px decreased in skin tissues. Systemic β-glucan significantly reversed the elevation of MDA levels and the reduction of SOD activities. β-glucan treatment also slightly enhanced the activity of CAT and prevented the depletion of GSH-Px activity caused by EMR, but not statistically significantly. The present study demonstrated the role of oxidative mechanisms in EMR-induced skin tissue damages and that β-glucan could ameliorate oxidative skin injury via its antioxidant properties.

  13. Late radiation injuries of the gastrointestinal tract in the H2 and H5 EORTC Hodgkin's disease trials: emphasis on the role of exploratory laparotomy and fractionation.

    PubMed

    Cosset, J M; Henry-Amar, M; Burgers, J M; Noordijk, E M; Van der Werf-Messing, B; Meerwaldt, J H; van der Schueren, E

    1988-09-01

    Out of 516 patients who entered in the two successive EORTC trials H2 and H5 for supra-diaphragmatic stages I and II Hodgkin's disease (HD), and who received an infra-diaphragmatic irradiation, 36 (7%) developed late radiation injuries of the gastrointestinal tract (GIT). Twenty-five patients presented with ulcers (stomach or duodenum), 2 with severe gastritis, 6 with small bowel obstruction or perforation and 3 patients had both an ulcer and bowel obstruction. A previous laparotomy played an important role. While the complication rate was 2.7% without any previous abdominal surgery, it was 11.5% after laparotomy (p less than 0.001). Fractionation was also found to be of importance in the occurrence of complications: three different weekly schedules were used -5 x 2 Gy, 4 x 2.5 Gy and 3 x 3.3 Gy; the GIT complication rates were 4, 9 and 22%, respectively (p less than 0.001). When combining laparotomy and fractionation, we found that the patients who were treated using 5 weekly fractions of 2 Gy without any prior laparotomy had a very low rate of late digestive complications (1%), whereas the patients who received 3 weekly fractions of 3.3 Gy after laparotomy presented a 39% complication rate. The other subgroups of patients were at an intermediate risk (from 5 to 13%) of late digestive injuries. Since most patients received 40 Gy with only very small variations, the influence of the radiation dose could not be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Delaying obsolescence.

    PubMed

    Lawlor, Rob

    2015-04-01

    This paper argues that those who emphasise that designers and engineers need to plan for obsolescence are too conservative. Rather, in addition to planning for obsolescence, designers and engineers should also think carefully about what they could do in order delay obsolescence. They should so this by thinking about the design itself, thinking of ways in which products could be useful and appealing for longer before becoming obsolete, as well thinking about the wider context in terms of the marketing of products, and also the social and legal. The paper also considers objections that these suggestions are unrealistically idealistic, failing to recognise the economic realities. I respond to these objections appealing to research in advertising, psychology, cognitive linguistics, philosophy, history, and economics, as well as drawing on the Statement of Ethical Principles developed by the Royal Academy of Engineering and the Engineering Council. PMID:24792878

  15. Thoracoabdominal injuries in the athlete.

    PubMed

    Amaral, J F

    1997-10-01

    Although thoracoabdominal injuries are uncommon in the athlete, they can be catastrophic if unrecognized or if diagnosis and treatment are delayed. This article reviews thoracic, intrathoracic, abdominal, and groin injuries in the athlete, and how they can be diagnosed and managed. PMID:9330811

  16. Experimental-clinical validation of the use of amitetravit, ATP and autologous bone marrow in radiation injuries caused by prolonged radiation

    NASA Technical Reports Server (NTRS)

    Atamanova, O. M.; Vodyakova, L. M.; Gvozdeva, N. I.; Davydova, S. A.; Ignasheva, L. P.; Rogozkin, V. D.; Sbitneva, M. F.; Ostroumova, L. M.; Tikhomirova, M. V.; Fedotenkov, A. G.

    1974-01-01

    Experimental clinical studies show that early pathogenetic treatment against the effects of prolonged radiation includes amitetravit as a means of increasing natural radio resistance, ATP as protective therapeutic agent, and automyelotransplantation for early pathogenetic treatment. The high effectiveness of the combined use of ATP and amitetravit in tests on dogs indicates an ability to prevent primary damages to genetic structures and accelerated processes of reparation in the first stages of radiopathological processes.

  17. Surgical considerations in the management of combined radiation blast injury casualties caused by a radiological dirty bomb.

    PubMed

    Williams, Geraint; O'Malley, Michael

    2010-09-01

    The capacity for surgical teams to respond appropriately to the consequences caused by the detonation of a radiological dirty bomb will be determined by prior knowledge, familiarity and training for this type unique terrorist event. This paper will focus on the surgical aspects of this scenario with particular emphasis on the management of combined trauma-radiological injury. The paper also describes some of the more serious explosion-contamination incidents from nuclear industrial sources, summarises learning points and parallels taken from these scenarios in relation to subject of a radiological dirty bomb and describes the likely radioactive substances involved. PMID:20149372

  18. Surgical considerations in the management of combined radiation blast injury casualties caused by a radiological dirty bomb.

    PubMed

    Williams, Geraint; O'Malley, Michael

    2010-09-01

    The capacity for surgical teams to respond appropriately to the consequences caused by the detonation of a radiological dirty bomb will be determined by prior knowledge, familiarity and training for this type unique terrorist event. This paper will focus on the surgical aspects of this scenario with particular emphasis on the management of combined trauma-radiological injury. The paper also describes some of the more serious explosion-contamination incidents from nuclear industrial sources, summarises learning points and parallels taken from these scenarios in relation to subject of a radiological dirty bomb and describes the likely radioactive substances involved.

  19. Development of a minipig model for lung injury induced by a single high-dose radiation exposure and evaluation with thoracic computed tomography

    PubMed Central

    Lee, Jong-Geol; Park, Sunhoo; Bae, Chang-Hwan; Jang, Won-Suk; Lee, Sun-Joo; Lee, Dal Nim; Myung, Jae Kyung; Kim, Cheol Hyeon; Jin, Young-Woo; Lee, Seung-Sook; Shim, Sehwan

    2016-01-01

    Radiation-induced lung injury (RILI) due to nuclear or radiological exposure remains difficult to treat because of insufficient clinical data. The goal of this study was to establish an appropriate and efficient minipig model and introduce a thoracic computed tomography (CT)-based method to measure the progression of RILI. Göttingen minipigs were allocated to control and irradiation groups. The most obvious changes in the CT images after irradiation were peribronchial opacification, interlobular septal thickening, and lung volume loss. Hounsfield units (HU) in the irradiation group reached a maximum level at 6 weeks and decreased thereafter, but remained higher than those of the control group. Both lung area and cardiac right lateral shift showed significant changes at 22 weeks post irradiation. The white blood cell (WBC) count, a marker of pneumonitis, increased and reached a maximum at 6 weeks in both peripheral blood and bronchial alveolar lavage fluid. Microscopic findings at 22 weeks post irradiation were characterized by widening of the interlobular septum, with dense fibrosis and an increase in the radiation dose–dependent fibrotic score. Our results also showed that WBC counts and microscopic findings were positively correlated with the three CT parameters. In conclusion, the minipig model can provide useful clinical data regarding RILI caused by the adverse effects of high-dose radiotherapy. Peribronchial opacification, interlobular septal thickening, and lung volume loss are three quantifiable CT parameters that can be used as a simple method for monitoring the progression of RILI. PMID:26712795

  20. Rapid passage signals induced by chirped quantum cascade laser radiation: K state dependent-delay effects in the nu2 band of NH3.

    PubMed

    Northern, J H; Ritchie, G A D; Smakman, E P; van Helden, J H; Cockburn, J; Duxbury, G

    2010-08-15

    In this Letter, a 10 microm quantum cascade laser operating in the intrapulse mode is used observe rapid passage (RP) effects within a 40 cm single-pass gas cell containing low pressures of NH(3). The laser tuning range allows the rotational states J=2 with K=0, 1, and 2 to be probed. We show that the RP structures change as a function of optical density and that the magnitude of the delay in the switch from absorption to emission as a function of increased gas pressure is dependent upon the initial value of K. These measurements are qualitatively well modeled using the Maxwell-Bloch equations.

  1. Toward Distinguishing Recurrent Tumor From Radiation Necrosis: DWI and MTC in a Gamma Knife–Irradiated Mouse Glioma Model

    SciTech Connect

    Perez-Torres, Carlos J.; Engelbach, John A.; Cates, Jeremy; Thotala, Dinesh; Yuan, Liya; Schmidt, Robert E.; Rich, Keith M.; Drzymala, Robert E.; Ackerman, Joseph J.H.; Garbow, Joel R.

    2014-10-01

    Purpose: Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose. Methods and Materials: Two MRI contrasts that are widely used in the clinic were chosen for application to a glioma/radiation-injury model: diffusion weighted imaging, from which the apparent diffusion coefficient (ADC) is obtained, and magnetization transfer contrast, from which the magnetization transfer ratio (MTR) is obtained. These metrics were evaluated longitudinally, first in each lesion type alone–glioma versus irradiation – and then in a combined irradiated glioma model. Results: MTR was found to be consistently decreased in all lesions compared to nonlesion brain tissue (contralateral hemisphere), with limited specificity between lesion types. In contrast, ADC, though less sensitive to the presence of pathology, was increased in radiation injury and decreased in tumors. In the irradiated glioma model, ADC also increased immediately after irradiation, but decreased as the tumor regrew. Conclusions: ADC is a better metric than MTR for differentiating glioma from radiation injury. However, MTR was more sensitive to both tumor and radiation injury than ADC, suggesting a possible role in detecting lesions that do not enhance strongly on T1-weighted images.

  2. Hamlet's delay.

    PubMed

    Dendy, E B

    2001-01-01

    This paper raises a question about Freud's understanding of Hamlet and offers a fresh psychoanalytic perspective on the play, emphasizing the psychological use made of Hamlet by the audience. It suggests Hamlet and Claudius both serve as sacrificial objects, scapegoats, for the audience, embodying, through a mechanism of both identification and disidentification, the fulfillment, punishment, and renunciation of the audience's forbidden (i.e. Oedipal) wishes. The play is thus seen to represent unconsciously a rite of sacrifice in which both Claudius and Hamlet, both the father and the son, are led, albeit circuitously, to the slaughter. The need for delay on the part of Hamlet is thus seen to arise not merely from Hamlet's psychology, whatever the audience may project onto it, but ultimately from the function (both sadistic and defensive) that the sacrificial spectacle, the play as a whole, serves for the audience. The paper also speculates somewhat on the role of tragic heroes and heroines in general, and points to the unconscious collusion that permits author and audience to make use of them. Finally, in an addendum, the paper discusses the work of René Girard, a nonpsychoanalytic thinker whose ideas nonetheless are somewhat similar to those presented here. PMID:12102022

  3. Head Injuries

    MedlinePlus

    ... before. Often, the injury is minor because your skull is hard and it protects your brain. But ... injuries can be more severe, such as a skull fracture, concussion, or traumatic brain injury. Head injuries ...

  4. Back Injuries

    MedlinePlus

    ... extending from your neck to your pelvis. Back injuries can result from sports injuries, work around the house or in the garden, ... back is the most common site of back injuries and back pain. Common back injuries include Sprains ...

  5. Radiation Proctopathy

    PubMed Central

    Grodsky, Marc B.; Sidani, Shafik M.

    2015-01-01

    Radiation therapy is a widely utilized treatment modality for pelvic malignancies, including prostate cancer, rectal cancer, and cervical cancer. Given its fixed position in the pelvis, the rectum is at a high risk for injury secondary to ionizing radiation. Despite advances made in radiation science, up to 75% of the patients will suffer from acute radiation proctitis and up to 20% may experience chronic symptoms. Symptoms can be variable and include diarrhea, bleeding, incontinence, and fistulization. A multitude of treatment options exist. This article summarizes the latest knowledge relating to radiation proctopathy focusing on the vast array of treatment options. PMID:26034407

  6. Radiation proctopathy.

    PubMed

    Grodsky, Marc B; Sidani, Shafik M

    2015-06-01

    Radiation therapy is a widely utilized treatment modality for pelvic malignancies, including prostate cancer, rectal cancer, and cervical cancer. Given its fixed position in the pelvis, the rectum is at a high risk for injury secondary to ionizing radiation. Despite advances made in radiation science, up to 75% of the patients will suffer from acute radiation proctitis and up to 20% may experience chronic symptoms. Symptoms can be variable and include diarrhea, bleeding, incontinence, and fistulization. A multitude of treatment options exist. This article summarizes the latest knowledge relating to radiation proctopathy focusing on the vast array of treatment options. PMID:26034407

  7. Diverse delayed effects in human lymphoblastoid cells surviving exposure to high-LET (56)Fe particles or low-LET (137)Cs gamma radiation

    NASA Technical Reports Server (NTRS)

    Evans, H. H.; Horng, M. F.; Ricanati, M.; Diaz-Insua, M.; Jordan, R.; Schwartz, J. L.

    2001-01-01

    To obtain information on the origin of radiation-induced genomic instability, we characterized a total of 166 clones that survived exposure to (56)Fe particles or (137)Cs gamma radiation, isolated approximately 36 generations after exposure, along with their respective control clones. Cytogenetic aberrations, growth alterations, responses to a second irradiation, and mutant frequencies at the Na(+)/K(+) ATPase and thymidine kinase loci were determined. A greater percentage of clones that survived exposure to (56)Fe particles exhibited instability (defined as clones showing one or more outlying characteristics) than in the case of those that survived gamma irradiation. The phenotypes of the unstable clones that survived exposure to (56)Fe particles were also qualitatively different from those of the clones that survived gamma irradiation. A greater percentage (20%) of the unstable clones that survived gamma irradiation than those that survived exposure to (56)Fe particles (4%) showed an altered response to the second irradiation, while an increase in the percentage of clones that had an outlying frequency of ouabain-resistant and thymidine kinase mutants was more evident in the clones exposed to (56)Fe particles than in those exposed to gamma rays. Growth alterations and increases in dicentric chromosomes were found only in clones with more than one alteration. These results underscore the complex nature of genomic instability and the likelihood that radiation-induced genomic instability arises from different original events.

  8. Delayed homicides and the proximate cause.

    PubMed

    Lin, Peter; Gill, James R

    2009-12-01

    Delayed homicides result from complications of remote injuries inflicted by "the hands of another." The investigation of delayed homicides may be a challenge due to a number of factors including: failure to report the death to the proper authorities, lack of ready and adequate documentation of the original injury and circumstances, and jurisdictional differences between the places of injury and death. The certification of these deaths also requires the demonstration of a pathophysiologic link between the remote injury and death. In sorting through these issues, it is helpful to rely upon the definition of the proximate cause of death. Over a 2-year period in New York City, there were 1211 deaths certified as homicide of which 42 were due to injuries sustained greater than 1 year before death. The survival interval ranged from 1.3 to 43.2 years. The most common immediate causes of death were: infections (22), seizures (7), and intestinal obstructions/hernias (6). Common patterns of complications included infection following a gunshot wound of the spinal cord, seizure disorder due to blunt head trauma, and intestinal obstruction/hernia due to adhesions from an abdominal stab wound. Spinal cord injuries resulted in paraplegia in 14 instances and quadriplegia in 8. The mean survival interval for paraplegics was 20.3 years and 14.8 years for quadriplegics; infections were a frequent immediate cause of death in both groups, particularly infections due to chronic bladder catheterization. The definition of proximate cause originated with civil law cases and was later applied to death certification as the proximate cause of death. The gradual extinction of the "year and a day rule" for the limitation of bringing homicide charges in delayed deaths may result in more of these deaths going to trial. Medical examiners/coroners must be able to explain the reasoning behind these death certifications and maintain consistent standards for the certification of all delayed deaths due

  9. The reduction of radiation damage to the spinal cord by post-irradiation administration of vasoactive drugs

    SciTech Connect

    Hornsey, S.; Myers, R.; Jenkinson, T. )

    1990-06-01

    Radiation induced white matter necrosis in the rat spinal cord is preceded by changes in permeability of the blood brain-barrier, reduced blood flow, and infarction so that the necrosis is an ischemic necrosis. Attempts have been made to modify this developing pathology by the administration of drugs post-irradiation but just prior to the changes in vascular permeability. Verapamyl, a calcium channel blocker, had no effect on the development of ataxia. Dipyridamole, a drug which increases blood flow and reduces thrombosis, delayed and reduced the onset of ataxia. A low iron diet and desferrioxamine which reduces reperfusion injury also delayed and reduced ataxia. These results support the thesis that vascular changes are an important pathway in the development of radiation necrosis and that reperfusion injury is an important factor in the development and exacerbation of radiation damage to the spinal cord.

  10. Radiation resistance and injury in starved Escherichia coli O157:H7 treated with electron-beam irradiation in 0.85% saline and in apple juice.

    PubMed

    Hong, Sujin; Mendonça, Aubrey F; Daraba, Aura; Shaw, Angela

    2014-11-01

    This study evaluated the influence of starvation on the radiation resistance and injury in Escherichia coli O157:H7, following electron beam irradiation in 0.85% (wt/vol) saline and in apple juice. Washed exponential-phase cells of E. coli O157:H7 that were grown in tryptic soy broth (TSB) at 35°C were starved in 0.85% saline (25°C) for 10 days. Exponential- or stationary-phase cells grown in TSB (35°C) served as controls. Samples of 0.85% saline or pasteurized apple juice, inoculated with control cells or cells starved for 8 days, were exposed to electron beam irradiation at doses ranging from 0.0 (control) to 0.70 kGy. The E. coli survivors were enumerated by plating diluted samples on tryptic soy agar or on Sorbitol McConkey agar and counting bacterial colonies after incubation (35°C) for 24 h. Starved cells consistently exhibited higher irradiation D-values than controls (p<0.05). The D-values for control and starved E. coli O157:H7 in 0.85% saline were 0.11 and 0.26 kGy, respectively; D-values in apple juice were 0.16, 0.19, and 0.33 kGy for exponential, stationary, and starved cells, respectively. Irradiation (0.70 kGy) of E. coli O157:H7 in apple juice reduced numbers of exponential- and stationary-phase cells by ∼4.32 and 3.74 logs, respectively, whereas starved cells were reduced by only 2.20 logs. Exponential-phase cells exhibited the lowest resistance to irradiation, and sublethal injury in survivors of this group was higher than that of stationary-phase or starved cells irradiated at 0.50 or 0.70 kGy (p<0.05). The results of this study indicate that starvation-induced stress cross-protects E. coli O157:H7 from ionizing radiation and should be considered an important factor when determining irradiation D-values for this pathogen.

  11. SU-C-BRA-07: Virtual Bronchoscopy-Guided IMRT Planning for Mapping and Avoiding Radiation Injury to the Airway Tree in Lung SAbR

    SciTech Connect

    Sawant, A; Modiri, A; Bland, R; Yan, Y; Ahn, C; Timmerman, R

    2015-06-15

    Purpose: Post-treatment radiation injury to central and peripheral airways is a potentially important, yet under-investigated determinant of toxicity in lung stereotactic ablative radiotherapy (SAbR). We integrate virtual bronchoscopy technology into the radiotherapy planning process to spatially map and quantify the radiosensitivity of bronchial segments, and propose novel IMRT planning that limits airway dose through non-isotropic intermediate- and low-dose spillage. Methods: Pre- and ∼8.5 months post-SAbR diagnostic-quality CT scans were retrospectively collected from six NSCLC patients (50–60Gy in 3–5 fractions). From each scan, ∼5 branching levels of the bronchial tree were segmented using LungPoint, a virtual bronchoscopic navigation system. The pre-SAbR CT and the segmented bronchial tree were imported into the Eclipse treatment planning system and deformably registered to the planning CT. The five-fraction equivalent dose from the clinically-delivered plan was calculated for each segment using the Universal Survival Curve model. The pre- and post-SAbR CTs were used to evaluate radiation-induced segmental collapse. Two of six patients exhibited significant segmental collapse with associated atelectasis and fibrosis, and were re-planned using IMRT. Results: Multivariate stepwise logistic regression over six patients (81 segments) showed that D0.01cc (minimum point dose within the 0.01cc receiving highest dose) was a significant independent factor associated with collapse (odds-ratio=1.17, p=0.010). The D0.01cc threshold for collapse was 57Gy, above which, collapse rate was 45%. In the two patients exhibiting segmental collapse, 22 out of 32 segments showed D0.01cc >57Gy. IMRT re-planning reduced D0.01cc below 57Gy in 15 of the 22 segments (68%) while simultaneously achieving the original clinical plan objectives for PTV coverage and OAR-sparing. Conclusion: Our results indicate that the administration of lung SAbR can Result in significant injury to

  12. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

    PubMed

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

    2009-12-01

    The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation. PMID:20041793

  13. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

    PubMed

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

    2009-12-01

    The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation.

  14. Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK.

    PubMed

    Toutounchian, Jordan J; Steinle, Jena J; Makena, Patrudu S; Waters, Christopher M; Wilson, Matthew W; Haik, Barrett G; Miller, Duane D; Yates, Charles R

    2014-01-01

    Radiation-induced damage to the retina triggers leukostasis, retinal endothelial cell (REC) death, and subsequent hypoxia. Resultant ischemia leads to visual loss and compensatory retinal neovascularization (RNV). Using human RECs, we demonstrated that radiation induced leukocyte adhesion through mechanisms involving p38MAPK, p53, and ICAM-1 activation. Additional phenotypic changes included p38MAPK-dependent tyrosine phosphorylation of the focal adhesion scaffolding protein, paxillin (Tyr118). The quinic acid derivative KZ-41 lessened leukocyte adhesion and paxillin-dependent proliferation via inhibition of p38MAPK-p53-ICAM-1 signaling. Using the murine oxygen-induced retinopathy (OIR) model, we examined the effect of KZ-41 on pathologic RNV. Daily ocular application of a KZ-41-loaded nanoemulsion significantly reduced both the avascular and neovascular areas in harvested retinal flat mounts when compared to the contralateral eye receiving vehicle alone. Our data highlight the potential benefit of KZ-41 in reducing both the retinal ischemia and neovascularization provoked by genotoxic insults. Further research into how quinic acid derivatives target and mitigate inflammation is needed to fully appreciate their therapeutic potential for the treatment of inflammatory retinal vasculopathies. PMID:24956278

  15. Nanoencapsulation of rice bran oil increases its protective effects against UVB radiation-induced skin injury in mice.

    PubMed

    Rigo, Lucas Almeida; da Silva, Cássia Regina; de Oliveira, Sara Marchesan; Cabreira, Thaíssa Nunes; de Bona da Silva, Cristiane; Ferreira, Juliano; Beck, Ruy Carlos Ruver

    2015-06-01

    Excessive UV-B radiation by sunlight produces inflammatory and oxidative damage of skin, which can lead to sunburn, photoaging, and cancer. This study evaluated whether nanoencapsulation improves the protective effects of rice bran oil against UVB radiation-induced skin damage in mice. Lipid-core nanocapsules containing rice bran oil were prepared, and had mean size around 200 nm, negative zeta potential (∼-9 mV), and low polydispersity index (<0.20). In order to allow application on the skin, a hydrogel containing the nanoencapsulated rice bran oil was prepared. This formulation was able to prevent ear edema induced by UVB irradiation by 60 ± 9%, when compared with a hydrogel containing LNC prepared with a mixture of medium chain triglycerides instead of rice bran oil. Protein carbonylation levels (biomarker of oxidative stress) and NF-κB nuclear translocation (biomarker of pro-inflammatory and carcinogenesis response) were reduced (81% and 87%, respectively) in animals treated with the hydrogel containing the nanoencapsulated rice bran oil. These in vivo results demonstrate the beneficial effects of nanoencapsulation to improve the protective properties of rice bran oil on skin damage caused by UVB exposure.

  16. Vascular Access Port Implantation and Serial Blood Sampling in a Gottingen Minipig (Sus scrofa domestica) Model of Acute Radiation Injury

    PubMed Central

    Moroni, Maria; Coolbaugh, Thea V; Mitchell, Jennifer M; Lombardini, Eric; Moccia, Krinon D; Shelton, Larry J; Nagy, Vitaly; Whitnall, Mark H

    2011-01-01

    Threats of nuclear and other radiologic exposures have been increasing, but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. Because of their similarity to humans in regard to physiology and anatomy, we are characterizing Gottingen minipigs as a model to aid the development of radiation countermeasures. Irradiated minipigs exhibit immunosuppression, severe thrombocytopenia, vascular leakage, and acute inflammation. These complications render serial acquisition of blood samples problematic. Vascular access ports (VAP) facilitate serial sampling, but their use often is complicated by infections and fibrin deposition. We demonstrate here the successful use of VAP for multiple blood samplings in irradiated minipigs. Device design and limited postoperative prophylactic antimicrobial therapy before irradiation were key to obtaining serial sampling, reducing swelling, and eliminating infection and skin necrosis at the implantation site. Modifications of previous protocols included the use of polydioxanone sutures instead of silk; eliminating chronic port access; single-use, sterile, antireflux prefilled syringes for flushing; strict aseptic weekly maintenance of the device, and acclimating animals to reduce stress. VAP remained functional in 19 of 20 irradiated animals for as long as 3 mo. The remaining VAP failed due to a small leak in the catheter, leading to clot formation. VAP-related sepsis occurred in 2 minipigs. Blood sampling did not cause detectable stress in nonanesthetized sham-irradiated animals, according to leukograms and clinical signs. PMID:21333166

  17. LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma

    PubMed Central

    Kong, Cheng; Zhu, Xiang-zhi; Lee, Tsair-Fwu; Feng, Ping-bo; Xu, Jian-hua; Qian, Pu-dong; Zhang, Lan-fang; He, Xia; Huang, Sheng-fu; Zhang, Yi-qin

    2016-01-01

    We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients. PMID:27210263

  18. LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma.

    PubMed

    Kong, Cheng; Zhu, Xiang-Zhi; Lee, Tsair-Fwu; Feng, Ping-Bo; Xu, Jian-Hua; Qian, Pu-Dong; Zhang, Lan-Fang; He, Xia; Huang, Sheng-Fu; Zhang, Yi-Qin

    2016-01-01

    We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients. PMID:27210263

  19. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor beta1 and tumor necrosis factor alpha.

    PubMed

    Xia, De-Hong; Xi, Lei; Xv, Chen; Mao, Wei-Dong; Shen, Wei-Sheng; Shu, Zhong-Qin; Yang, Hong-Zhi; Dai, Min

    2010-09-01

    The aim of this article was to investigate the effect of ambroxol on radiation lung injury and the expression of transforming growth factor beta(1) (TGF-beta(1)), as well as tumor necrosis factor alpha (TNF-alpha) in plasma. Totally, 120 patients with locally advanced lung cancer in radiotherapy were randomized into treatment and control groups. Patients in the treatment group took ambroxol orally at a dosage of 90 mg, three times per day for 3 months from the beginning of radiotherapy. The expression of TGF-beta(1) and TNF-alpha in plasma was analyzed. The clinical symptoms and lung diffusing capacity were monitored using high resolving power computed tomography. The level of TGF-beta(1) in the control group was increased (11.8 +/- 5.5 ng/ml), whereas in ambroxol-treated patients, the increase was not significant (5.6 +/- 2.6 ng/ml, P < 0.001). Radiotherapy-induced elevation of TNF-alpha levels, seen in control patients, was also abolished after treatment with ambroxol (5.1 +/- 1.0 vs. 2.4 +/- 0.8 ng/ml, P < 0.001). In the treatment group, carbon monoxide diffusion capacity was not significantly decreased at 6, 12, and 18 months post-radiotherapy, compared with the control group (P < 0.05). Ambroxol decreased the expression of TGF-beta(1) and TNF-alpha, and minimized the diminishment of lung diffusion capacity after radiotherapy.

  20. Time delay and distance measurement

    NASA Technical Reports Server (NTRS)

    Abshire, James B. (Inventor); Sun, Xiaoli (Inventor)

    2011-01-01

    A method for measuring time delay and distance may include providing an electromagnetic radiation carrier frequency and modulating one or more of amplitude, phase, frequency, polarization, and pointing angle of the carrier frequency with a return to zero (RZ) pseudo random noise (PN) code. The RZ PN code may have a constant bit period and a pulse duration that is less than the bit period. A receiver may detect the electromagnetic radiation and calculate the scattering profile versus time (or range) by computing a cross correlation function between the recorded received signal and a three-state RZ PN code kernel in the receiver. The method also may be used for pulse delay time (i.e., PPM) communications.

  1. Delayed onset arterial gas embolism.

    PubMed

    Moloff, A L

    1993-11-01

    Numerous civilian and military personnel are involved in SCUBA diving activities. In this day of rapid air travel it is important that all physicians, not just those living near the coast or dive centers, be familiar with the basics of diagnosing and treating diving-related injuries. One of the more serious complications of dysbarism is Arterial Gas Embolism (AGE). This case history involves an atypical presentation of delayed onset AGE in a military diver trainee, and its treatment. This article then reviews the incidence, etiology, pathophysiology, "classic" presentation and current treatment of this disease. Systemic pathophysiology secondary to the effects of intravascular air of AGE is also discussed.

  2. [Mechanism of injury of air-dry pea seeds under the influence of low doses of gamma-radiation].

    PubMed

    Veselova, T V; Veselovskiĭ, V A

    2012-01-01

    The aim of this work was to determine which processes in air-dry seeds result in bimodal changes of the pea seed quality under the influence of low doses of gamma-radiation. Pea seeds (cv. "Nemchinovsky-85", harvest 2006, 82% germination persentage) were exposed to gamma-radiation at doses of 3, 10 and 100 Gy The germination percentage decreased to 45% four days after irradiation at the dose of 3 Gy, rised up to 87% at doses of 10 Gy, while the dose of 100 Gy killed the most part of seeds. Seed fractions differing in quality were selected using the metod of Room temperature phosphorecsence (RTP): strong seed frasction I from non-irradiated seeds; weak seed fraction II from the seeds irradiated at a dose of 3 Gy; dead seeds from the seeds irradiated at a dose of 100 Gy. ThermoChemiLuminecnsece (TCL) of seed powders and cotyledons was used. It was shown that the increase of the TCL level in the temperature range from 50 to 110 degreesC was associated with the lipid peroxidation products. The TCL level of seeds subjected to gamma-irradiation at a dose of 3 Gy was similar to that of non-irradiated seeds in the temperature range 50 to 100 degreesC. Therefore, lipid peroxidation was not the cause of the abnormal seedling appearance. The TCL level within this temperature range was increased only in seeds subjected to y-irradiation at a dose of 100 Gy. The TCL level at 150 degreesC was in proportion with the exogenous glucose amount. The increased TCL level of seeds subjected to y-irradiation at a dose of 3 Gy at 150 degreesC resulted from the increase of the glucose content. This means that the transition from the fraction of strong seeds into the fraction of weak ones was the result of the activation of hydrolysis processes. Decrease in the water content of seeds testified to utilization of bound water in this process. The decrease of the glucose content in the "improved" seeds subjected to gamma-irradiation at a dose of 10 Gy most probably indicates the participation of

  3. Radiation protection in space.

    PubMed

    Reitz, G; Facius, R; Sandler, H

    1995-01-01

    Radiation environment, basic concepts of radiation protection, and specific aspects of the space radiation field are reviewed. The discussion of physico-chemical and subcellular radiation effects includes mechanisms of radiation action and cellular consequences. The discussion of radiobiological effects includes unique aspects of HZE particle effects, space flight findings, terrestrial findings, analysis of somatic radiation effects and effects on critical organs, and early and delayed effects. Other topics include the impact of the space flight environment, measurement of radiation exposure, establishing radiation protection limits, limitations in establishing space-based radiation exposure limits, radiation protection measures, and recommendations. PMID:11541474

  4. Electrophysiologic evidence of subclinical injury to the posterior columns of the human spinal cord after therapeutic radiation

    SciTech Connect

    Dorfman, L.J.; Donaldson, S.S.; Gupta, P.R.; Bosley, M.D.

    1982-12-15

    Spinal somatosensory conduction velocity (SSCV) was indirectly estimated from cerebral evoked potentials in 15 adults who had received therapeutic radiation (RT) (2000-4380 rad) to the thoracic spinal cord during treatment for lung cancer, and in 15 age-matched normal controls. Thirteen of the patients had also received 4400-5500 rad to the supraclavicular fossae. One-way impulse conduction time in the arm, estimated from F-wave latency, was prolonged in the patients as compared to controls but conduction time in the leg was similar in the two groups. SSCV was significantly slower in the patient group whereas supraspinal latency (cervical cord to cortex) was identical. SSCV in the patient group was not related to total RT dose but was correlated with both treatment time and number of fractions. These findings suggest that RT may produce subclinical spinal cord dysfunction even at conventional dosage schedules, and that it may be possible physiologically to monitor the myelopathic effects of RT in individual patients.

  5. Electrophysiologic evidence of subclinical injury to the posterior columns of the human spinal cord after therapeutic radiation

    SciTech Connect

    Dorfman, L.J.; Donaldson, S.S.; Gupta, P.R.; Bosley, T.M.

    1982-12-15

    Spinal somatosensory conduction velocity (SSCV) was indirectly estimated from cerebral evoked potentials in 15 adults who had received therapeutic radiation (RT) (2000-4380 rad) to the thoracic spinal cord during treatment for lung cancer, and in 15 age-matched normal controls. Thirteen of the patients had also received 4400-5500 rad to the supraclavicular fossae. One-way impulse conduction time in the arm, estimated from F-wave latency, was prolonged in the patients as compared to controls (12.0 +/- 1.2 versus 10.4 +/- 1.0 msec; P less than 0.001) but conduction time in the leg was similar in the two groups (22.4 +/- 2.4 versus 22.0 +/- 2.5 msec; P less than 0.1). SSCV was significantly slower in the patient group (37.9 +/- 13.9 versus 54.5 +/- 12.9 m/sec; P less than 0.001) whereas supraspinal latency (cervical cord to cortex) was identical (5.5 +/- 0.9 versus 5.5 +/- 0.8 msec; P less than 0.1). SSCV in the patient group was not related to total RT dose (r . 0.15; P . 0.2), but was correlated with both treatment time and number of fractions (r . 0.49 and 0.43; P . 0.003 and 0.007, respectively). These findings suggest that RT may produce subclinical spinal cord dysfunction even at conventional dosage schedules, and that it may be possible physiologically to monitor the myelopathic effects of RT in individual patients.

  6. Delayed effects of A-bomb radiation: a review of recent mortality rates and risk estimates for five-year survivors.

    PubMed

    Stewart, A M

    1982-06-01

    A review of published data relating to A-bomb survivors has led to the conclusion that since they were based on the mortality experiences of five year survivors estimates of radiation effects should have been controlled for two opposing forces-namely, selective survival of exceptionally fit individuals during the period of heavy acute mortality and residual disabilities. Both effects were dose-related and beyond question, and the disabilities probably included the effects of incomplete repair of bone marrow damage. Therefore, in addition to differences between high and low dose being largely obliterated, there was probably distortion of cancer effects. The two opposing forces are clearly the reason why the change from the high mortality rates of 1945-6 to the low rates of the 1950s was not accompanied by a change from a position to a negative association with dose, and imperviousness to the residual disabilities is probably the reason why sudden deaths of previously healthy individuals (exemplified by suicides) were an exception to this rule. Finally, impairment of bone marrow function probably accounts for the early epidemic of myeloid leukaemia; the apparent absence of other cancers at this time, and the relatively high dose-related death rates for blood diseases other than leukaemia.

  7. Head Injuries

    MedlinePlus

    ... injuries internal head injuries, which may involve the skull, the blood vessels within the skull, or the brain Fortunately, most childhood falls or ... knock the brain into the side of the skull or tear blood vessels. Some internal head injuries ...

  8. Eye Injuries

    MedlinePlus

    The structure of your face helps protect your eyes from injury. Still, injuries can damage your eye, sometimes severely enough that you could lose your vision. Most eye injuries are preventable. If you play sports or ...

  9. Blast Injuries

    MedlinePlus

    ... Service Members & Veterans Family & Caregivers Medical Providers Blast Injuries U.S. Army photo by Sgt. Gustavo Olgiati How ... tertiary injury Does a blast cause different brain injuries than blunt trauma? There currently is no evidence ...

  10. Sports Injuries

    MedlinePlus

    ... sometimes you can injure yourself when you play sports or exercise. Accidents, poor training practices, or improper ... can also lead to injuries. The most common sports injuries are Sprains and strains Knee injuries Swollen ...

  11. Hamstring injuries.

    PubMed

    Ropiak, Christopher R; Bosco, Joseph A

    2012-01-01

    Hamstring injuries are a frequent injury in athletes. Proximal injuries are common, ranging from strain to complete tear. Strains are managed nonoperatively, with rest followed by progressive stretching and strengthening. Reinjury is a concern. High grade complete tears are better managed surgically, with reattachment to the injured tendon or ischial tuberosity. Distal hamstring injury is usually associated with other knee injuries, and isolated injury is rare.

  12. Suppression of 125I-uptake in mouse thyroid by seaweed feeding: possible preventative effect of dietary seaweed on internal radiation injury of the thyroid by radioactive iodine.

    PubMed

    Maruyama, H; Yamamoto, I

    1992-12-01

    We conducted an animal experiment to determine how dietary seaweeds rich in iodine and dietary fibers suppress radioactive iodine uptake by the thyroid, using mice and four kinds of experimental diets, three with 1% or 2% powdered fronds of the kelp Laminaria religiosa and 2% powdered laver Porphyra yezoensis, and one with cellulose. Iodine content of a hot-water extract of the kelp was 0.530 +/- 0.001%, and its dietary fiber (DF) values were 52.8 +/- 1.2%. Iodine in an extract of the laver was 0.008 +/- 0.001%, and its DF values were 41.4% +/- 0.7%. A statistically significant reduction of 125I uptake by the thyroid, 3 hours after intragastric administration of the radionuclide at a dosage of 18.5 kBq or 185 kBq in 0.3 ml aqueous solution per mouse, was observed in mice previously fed the experimental diets containing 1% and 2% kelp during periods varying from 24 hours to 7 days. The degree of the suppression was observed to depend on the amount of iodine in the diet or in the injected sample, no matter whether organic or inorganic, judging from the results of an additional experiment. Thus, we conclude that previously fed iodine-rich material, especially dietary seaweeds rich in iodine and other minerals, vitamins, and beta-carotene, such as kelps or laver supplemented with inorganic iodine, may be effective in prevention of internal radiation injury of the thyroid. PMID:1344008

  13. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

    PubMed Central

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  14. Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients. Methods/design This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015. Discussion This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances. Trial registration ClinicalTrials.gov identifier NCT01682590, registered on 10 September 2012. PMID:24998258

  15. Laser eye injuries.

    PubMed

    Barkana, Y; Belkin, M

    2000-01-01

    Laser instruments are used in many spheres of human activity, including medicine, industry, laboratory research, entertainment, and, notably, the military. This widespread use of lasers has resulted in many accidental injuries. Injuries are almost always retinal, because of the concentration of visible and near-infrared radiation on the retina. The retina is therefore the body tissue most vulnerable to laser radiation. The nature and severity of this type of retinal injury is determined by multiple laser-related and eye-related factors, the most important being the duration and amount of energy delivered and the retinal location of the lesion. The clinical course of significant retinal laser injuries is characterized by sudden loss of vision, often followed by marked improvement over a few weeks, and occasionally severe late complications. Medical and surgical treatment is limited. Laser devices hazardous to the human eye are currently in widespread use by armed forces. Furthermore, lasers may be employed specifically for visual incapacitation on future battlefields. Adherence to safety practices effectively prevents accidental laser-induced ocular injuries. However, there is no practical way to prevent injuries that are maliciously inflicted, as expected from laser weapons.

  16. Attosecond Delays in Resonant Photoionization

    NASA Astrophysics Data System (ADS)

    Maquet, Alfred

    2015-05-01

    Attosecond delays in the photoionization of atomic states have been evidenced in recent experiments performed in the 2010's. The delays were associated to the emission of photoelectron wave packets ejected from different atomic states, in the combined presence of attosecond pulses of XUV radiation and of a synchronized IR laser pulse, the latter being used as a reference ``clock''. These experiments were performed at XUV frequencies connecting the ground state to a ``flat'' continuum. Theoretical treatments were able to relate the measured delays to Wigner's definition of time delays in terms of the energy derivative of the phase-shift attached to the continuum wave functions of the photoelectrons. Attention has recently shifted towards the case of resonant photoionization in the course of which the XUV frequency is tuned close to a resonance of the target system. The case of a transition towards an autoionizing states of the target is particularly interesting as it makes evident the role of electronic correlations. Here, we shall present recent advances realized in the theoretical interpretation of this new class of experiments.

  17. Iatrogenic accessory nerve injury.

    PubMed Central

    London, J.; London, N. J.; Kay, S. P.

    1996-01-01

    Accessory nerve injury produces considerable disability. The nerve is most frequently damaged as a complication of radical neck dissection, cervical lymph node biopsy and other surgical procedures. The problem is frequently compounded by a failure to recognise the error immediately after surgery when surgical repair has the greatest chance of success. We present cases which outline the risk of accessory nerve injury, the spectrum of clinical presentations and the problems produced by a failure to recognise the deficit. Regional anatomy, consequences of nerve damage and management options are discussed. Diagnostic biopsy of neck nodes should not be undertaken as a primary investigation and, when indicated, surgery in this region should be performed by suitably trained staff under well-defined conditions. Awareness of iatrogenic injury and its consequences would avoid delays in diagnosis and treatment. Images Figure 2 PMID:8678450

  18. Nerve Injuries in Athletes.

    PubMed

    Collins, K; Storey, M; Peterson, K; Nutter, P

    1988-01-01

    In brief: Nerve injuries in athletes may be serious and may delay or prevent an athlete's return to his or her sport. Over a two-year period, the authors evaluated the condition of 65 patients who had entrapments of a nerve or nerve root, documented with electromyography. They describe four case histories: Two patients had radial nerve entrapments, one caused by baseball pitching and the other by kayaking; one football player had combined suprascapular neuropathy and upper trunk brachial plexopathy; and one patient had carpal tunnel syndrome of a median nerve secondary to rowing. Sports-related peripheral nerve lesions of the lower extremity were not seen during the study period. Based on a literature review, the nerve injuries discussed represent the spectrum of nerve entrapments likely to be seen in US clinics. The authors conclude that peripheral nerve lesions should be considered in the differential diagnosis of sports injuries, particularly at the shoulder, elbow, and wrist.

  19. Speech and Language Delay

    MedlinePlus

    MENU Return to Web version Speech and Language Delay Overview How do I know if my child has speech delay? Every child develops at his or her ... of the same age, the problem may be speech delay. Your doctor may think your child has ...

  20. Delay Discounting and Gambling

    PubMed Central

    Madden, Gregory J.; Francisco, Monica T.; Brewer, Adam T.; Stein, Jeffrey S.

    2011-01-01

    Delay discounting describes the decline in the value of a reinforcer as the delay to that reinforcer increases. A review of the available studies revealed that steep delay discounting is positively correlated with problem or pathological gambling. One hypothesis regarding this correlation derives from the discounting equation proposed by Mazur (1989). According to the equation, steeper discounting renders the difference between fixed-delayed rewards and gambling-like variable-delayed rewards larger; with the latter being more valuable. The present study was designed to test this prediction by first assessing rats’ impulsive choices across four delays to a larger-later reinforcer. A second condition quantified strength of preference for mixed- over fixed-delays, with the duration of the latter adjusted between sessions to achieve indifference. Strength of preference for the mixed-delay alternative is given by the fixed delay at indifference (lower fixed-delay values reflect stronger preferences). Percent impulsive choice was not correlated with the value of the fixed delay at indifference and, therefore, the prediction of the hyperbolic model of gambling was not supported. A follow-up assessment revealed a significant decrease in impulsive choice after the second condition. This shift in impulsive choice could underlie the failure to observe the predicted correlation between impulsive choice and degree of preference for mixed- over fixed delays. PMID:21352902

  1. Prophylaxis against radiation injury. The use of elemental diet prior to and during radiotherapy for invasive bladder cancer and in early postoperative feeding following radical cystectomy and ileal conduit

    SciTech Connect

    McArdle, A.H.; Reid, E.C.; Laplante, M.P.; Freeman, C.R.

    1986-08-01

    Previous studies done in animals have shown that significant prophylaxis against radiation injury could be afforded by feeding an elemental diet (ED) for three days before and during radiation. In the present study 20 patients were fed an ED for three days before and for the four days during radiotherapy (five fractions of 400 rad (4 Gy) each) prior to radical cystectomy and ileal conduit for invasive bladder cancer; ED feeding was recommenced 24 hours postoperatively via a feeding jejunostomy. The ED-fed patients exhibited positive nitrogen balance preoperatively and had an early return to positive nitrogen balance postoperatively (3.60 +/- 0.32 days). There was also prompt return of bowel sounds (3.00 +/- 0.32 days). Histologically and ultrastructurally, biopsy specimens of the ileal mucosa showed normal morphologic findings, with maintenance of normal levels of enzyme activity in the brush border. Severe or bloody diarrhea was absent in these patients. These data suggest that ED feeding provides prophylaxis against the acute phase of radiation injury in patients undergoing high-dose, short-course radiotherapy for invasive bladder cancer and that it is a safe and feasible means of postoperative nutritional support, even in the presence of a fresh bowel anastomosis.

  2. Biophysics and medical effects of enhanced radiation weapons.

    PubMed

    Reeves, Glen I

    2012-08-01

    Enhanced radiation weapons (ERW) are fission-fusion devices where the massive numbers of neutrons generated during the fusion process are intentionally allowed to escape rather than be confined to increase yield (and fallout products). As a result, the energy partition of the weapon output shifts from blast and thermal energies toward prompt radiation. The neutron/gamma output ratio is also increased. Neutrons emitted from ERW are of higher energy than the Eave of neutrons from fission weapons. These factors affect the patterns of injury distribution; delay wound healing in combined injuries; reduce the therapeutic efficacy of medical countermeasures; and increase the dose to radiation-only casualties, thus potentiating the likelihood of encountering radiation-induced incapacitation. The risk of radiation-induced carcinogenesis is also increased. Radiation exposure to first responders from activation products is increased over that expected from a fission weapon of similar yield. However, the zone of dangerous fallout is significantly reduced in area. At least four nations have developed the potential to produce such weapons. Although the probability of detonation of an ERW in the near future is very small, it is nonzero, and clinicians and medical planners should be aware of the medical effects of ERW.

  3. Pancreatic injury.

    PubMed

    Ahmed, Nasim; Vernick, Jerome J

    2009-12-01

    Injury to the pancreas, because of its retroperitoneal location, is a rare occurrence, most commonly seen with penetrating injuries (gun shot or stab wounds). Blunt trauma to the pancreas accounts for only 25% of the cases. Pancreatic injuries are associated with high morbidity and mortality due to accompanying vascular and duodenal injuries. Pancreatic injuries are not always easy to diagnose resulting in life threatening complications. Physical examination as well as serum amylase is not diagnostic following blunt trauma. Computed tomography (CT) scan can delineate the injury or transaction of the pancreas. Endoscopic retrograde pancreaticography (ERCP) is the main diagnostic modality for evaluation of the main pancreatic duct. Unrecognized ductal injury leads to pancreatic pseudocyst, fistula, abscess, and other complications. Management depends upon the severity of the pancreatic injury as well as associated injuries. Damage control surgery in hemodynamic unstable patients reduces morbidity and mortality.

  4. Snowboard injuries.

    PubMed

    Pino, E C; Colville, M R

    1989-01-01

    A retrospective survey of 267 snowboarders was undertaken to determine the population at risk and types and mechanisms of injuries sustained in this sport. Snowboarders are young (average age, 21 years), male (greater than 90%), view themselves in average or above average physical condition (96%), and have varied sports interests. One hundred ten injuries that resulted in a physician visit were reported. Ligament sprains, fractures, and contusions were the most frequent types of injury. Fifty percent of all injuries occurred in the lower extremities, with ankle injuries being the most common. Snowboard riders using equipment with increased ankle support seem to be more protected from lower extremity injuries. The lower extremity injuries were concentrated in the forward limb of the snowboarder, where the rider's weight is disproportionately distributed. Differences in the mechanism and spectrum of injury between snowboarding and skiing injuries were noted, including: impact rather than torsion as the major mechanism of injury, a significant lack of thumb injuries, comparative increase in ankle injuries, a decrease in knee injuries, and a higher percentage of upper extremity injuries.

  5. Basketball injuries.

    PubMed

    Newman, Joel S; Newberg, Arthur H

    2010-11-01

    Basketball injuries are most prevalent in the lower extremity, especially at the ankle and knee. Most basketball injuries are orthopedic in nature and commonly include ligament sprains, musculotendinous strains, and overuse injuries including stress fractures. By virtue of its excellent contrast resolution and depiction of the soft tissues and trabecular bone, magnetic resonance imaging has become the principal modality for evaluating many basketball injuries. In this article, commonly encountered basketball injuries and their imaging appearances are described. The epidemiology of basketball injuries across various age groups and levels of competition and between genders are reviewed.

  6. Skateboard injuries.

    PubMed

    Cass, D T; Ross, F

    1990-08-01

    The recent increase in skateboard injuries is causing concern. Over a 30-month period there were 80 admissions (69 children) to Westmead Hospital because of skateboard injuries. Among children most injuries were minor, involving fractures to the upper limbs (47) or minor head injuries (8). The only serious injuries were a ruptured urethra and a closed head injury. Over the same time period skateboard riding caused five deaths in New South Wales. These all involved head injuries and in four instances collisions with cars. The data strongly support other studies that show skateboard riding is particularly dangerous near traffic and should be proscribed. However, in parkland and around the home the skateboard is an enjoyable toy with an acceptable risk of minor injury. Helmets should be worn and would have prevented all the head injury admissions in this series. Children under 10 have a higher risk of fractures and head injuries due to insufficient motor development to control the boards and the resultant falls. Skateboard injuries are an example of injuries caused by a "fad epidemic". To cope with these types of periodic events up-to-date data collection is needed, followed rapidly by an intervention programme so that serious injuries can be kept to a minimum.

  7. Corneal injury

    MedlinePlus

    ... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...

  8. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  9. Spinal injury

    MedlinePlus

    ... head. Alternative Names Spinal cord injury; SCI Images Skeletal spine Vertebra, cervical (neck) Vertebra, lumbar (low back) Vertebra, thoracic (mid back) Vertebral column Central nervous system Spinal cord injury Spinal anatomy Two person roll - ...

  10. Delayed reconstruction of a quadriceps tendon.

    PubMed

    Pocock, C A J; Trikha, S P; Bell, J S P

    2008-01-01

    Rupture of the quadriceps tendon is an uncommon injury and rapid diagnosis is important because delay in surgical repair generally is believed to adversely affect outcome. One study of 20 patients suggests repair should be done during the first 48 to 72 hours postinjury to achieve a successful outcome and late repair led to unsatisfactory recovery. Cases of delayed tendon repair have been reported, the longest to our knowledge being 11 months before surgical intervention. We present a case of successful outcome of a quadriceps tendon rupture reconstructed at least 8 years after occurrence and a review of the literature of delayed reconstructions. We show that successful restoration of extensor mechanism function can be achieved several years after tendon rupture.

  11. Delayed transient post-traumatic quadriplegia.

    PubMed

    Al-Shaaibi, Khaloud; Kariyattil, Rajeev

    2015-03-01

    Transient neurological deficit following cervical trauma have been reported following sports injuries, and has been referred to as cervical cord neurapraxia. The so-called "whiplash injuries" following minor motor vehicle collisions usually do not produce any neurological deficit. Here we report the case of a whiplash type of injury presenting with a delayed onset neurological deficit, which was followed by rapid and complete recovery. The patient, an otherwise healthy 34-year-old male, attended the emergency department of Sultan Qaboos University Hospital following a rear-end motor vehicle collision. We present images showing degenerative disc disease causing spinal canal narrowing and mild cord compression in the patient, but no spinal instability. Differential diagnoses are also discussed. PMID:25960840

  12. CGI delay compensation

    NASA Technical Reports Server (NTRS)

    Mcfarland, Richard E.

    1986-01-01

    Computer-generated graphics in real-time helicopter simulation produces objectionable scene-presentation time delays. In the flight simulation laboratory at Ames Research Center, it has been determined that these delays have an adverse influence on pilot performance during aggressive tasks such as nap-of-the-earth (NOE) maneuvers. Using contemporary equipment, computer-generated image (CGI) time delays are an unavoidable consequence of the operations required for scene generation. However, providing that magnitide distortions at higher frequencies are tolerable, delay compensation is possible over a restricted frequency range. This range, assumed to have an upper limit of perhaps 10 or 15 rad/sec, conforms approximately to the bandwidth associated with helicopter handling qualities research. A compensation algorithm is introduced here and evaluated in terms of tradeoffs in frequency responses. The algorithm has a discrete basis and accommodates both a large, constant transport delay interval and a periodic delay interval, as associated with asynchronous operations.

  13. Radiation accidents

    SciTech Connect

    Saenger, E.L.

    1986-09-01

    It is essential that emergency physicians understand ways to manage patients contaminated by radioactive materials and/or exposed to external radiation sources. Contamination accidents require careful surveys to identify the metabolic pathway of the radionuclides to guide prognosis and treatment. The level of treatment required will depend on careful surveys and meticulous decontamination. There is no specific therapy for the acute radiation syndrome. Prophylactic antibodies are desirable. For severely exposed patients treatment is similar to the supportive care given to patients undergoing organ transplantation. For high-dose extremity injury, no methods have been developed to reverse the fibrosing endarteritis that eventually leads to tissue death so frequently found with this type of injury. Although the Three Mile Island episode of March 1979 created tremendous public concern, there were no radiation injuries. The contamination outside the reactor building and the release of radioiodine were negligible. The accidental fuel element meltdown at Chernobyl, USSR, resulted in many cases of acute radiation syndrome. More than 100,000 people were exposed to high levels of radioactive fallout. The general principles outlined here are applicable to accidents of that degree of severity.

  14. Radiation accidents.

    PubMed

    Saenger, E L

    1986-09-01

    It is essential that emergency physicians understand ways to manage patients contaminated by radioactive materials and/or exposed to external radiation sources. Contamination accidents require careful surveys to identify the metabolic pathway of the radionuclides to guide prognosis and treatment. The level of treatment required will depend on careful surveys and meticulous decontamination. There is no specific therapy for the acute radiation syndrome. Prophylactic antibodies are desirable. For severely exposed patients treatment is similar to the supportive care given to patients undergoing organ transplantation. For high-dose extremity injury, no methods have been developed to reverse the fibrosing endarteritis that eventually leads to tissue death so frequently found with this type of injury. Although the Three Mile Island episode of March 1979 created tremendous public concern, there were no radiation injuries. The contamination outside the reactor building and the release of radioiodine were negligible. The accidental fuel element meltdown at Chernobyl, USSR, resulted in many cases of acute radiation syndrome. More than 100,000 people were exposed to high levels of radioactive fallout. The general principles outlined here are applicable to accidents of that degree of severity. PMID:3526994

  15. Delayed recombination and standard rulers

    SciTech Connect

    De Bernardis, Francesco; Melchiorri, Alessandro; Bean, Rachel; Galli, Silvia; Silk, Joseph I.; Verde, Licia

    2009-02-15

    Measurements of baryonic acoustic oscillations (BAOs) in galaxy surveys have been recognized as a powerful tool for constraining dark energy. However, this method relies on the knowledge of the size of the acoustic horizon at recombination derived from cosmic microwave background (CMB) anisotropy measurements. This estimate is typically derived assuming a standard recombination scheme; additional radiation sources can delay recombination altering the cosmic ionization history and the cosmological inferences drawn from CMB and BAO data. In this paper we quantify the effect of delayed recombination on the determination of dark energy parameters from future BAO surveys such as the Baryon Oscillation Spectroscopic Survey and the Wide-Field Multi-Object Spectrograph. We find the impact to be small but still not negligible. In particular, if recombination is nonstandard (to a level still allowed by CMB data), but this is ignored, future surveys may incorrectly suggest the presence of a redshift-dependent dark energy component. On the other hand, in the case of delayed recombination, adding to the analysis one extra parameter describing deviations from standard recombination does not significantly degrade the error bars on dark energy parameters and yields unbiased estimates. This is due to the CMB-BAO complementarity.

  16. VARIABLE TIME DELAY MEANS

    DOEpatents

    Clemensen, R.E.

    1959-11-01

    An electrically variable time delay line is described which may be readily controlled simuitaneously with variable impedance matching means coupied thereto such that reflections are prevented. Broadly, the delay line includes a signal winding about a magnetic core whose permeability is electrically variable. Inasmuch as the inductance of the line varies directly with the permeability, the time delay and characteristic impedance of the line both vary as the square root of the permeability. Consequently, impedance matching means may be varied similariy and simultaneously w:th the electrically variable permeability to match the line impedance over the entire range of time delay whereby reflections are prevented.

  17. Delayed recombination and cosmic parameters

    SciTech Connect

    Galli, Silvia; Melchiorri, Alessandro; Bean, Rachel; Silk, Joseph

    2008-09-15

    Current cosmological constraints from cosmic microwave background anisotropies are typically derived assuming a standard recombination scheme, however additional resonance and ionizing radiation sources can delay recombination, altering the cosmic ionization history and the cosmological inferences drawn from the cosmic microwave background data. We show that for recent observations of the cosmic microwave background anisotropy, from the Wilkinson microwave anisotropy probe satellite mission (WMAP) 5-year survey and from the arcminute cosmology bolometer array receiver experiment, additional resonance radiation is nearly degenerate with variations in the spectral index, n{sub s}, and has a marked effect on uncertainties in constraints on the Hubble constant, age of the universe, curvature and the upper bound on the neutrino mass. When a modified recombination scheme is considered, the redshift of recombination is constrained to z{sub *}=1078{+-}11, with uncertainties in the measurement weaker by 1 order of magnitude than those obtained under the assumption of standard recombination while constraints on the shift parameter are shifted by 1{sigma} to R=1.734{+-}0.028. From the WMAP5 data we obtain the following constraints on the resonance and ionization sources parameters: {epsilon}{sub {alpha}}<0.39 and {epsilon}{sub i}<0.058 at 95% c.l.. Although delayed recombination limits the precision of parameter estimation from the WMAP satellite, we demonstrate that this should not be the case for future, smaller angular scales measurements, such as those by the Planck satellite mission.

  18. Delayed recombination and cosmic parameters

    NASA Astrophysics Data System (ADS)

    Galli, Silvia; Bean, Rachel; Melchiorri, Alessandro; Silk, Joseph

    2008-09-01

    Current cosmological constraints from cosmic microwave background anisotropies are typically derived assuming a standard recombination scheme, however additional resonance and ionizing radiation sources can delay recombination, altering the cosmic ionization history and the cosmological inferences drawn from the cosmic microwave background data. We show that for recent observations of the cosmic microwave background anisotropy, from the Wilkinson microwave anisotropy probe satellite mission (WMAP) 5-year survey and from the arcminute cosmology bolometer array receiver experiment, additional resonance radiation is nearly degenerate with variations in the spectral index, ns, and has a marked effect on uncertainties in constraints on the Hubble constant, age of the universe, curvature and the upper bound on the neutrino mass. When a modified recombination scheme is considered, the redshift of recombination is constrained to z*=1078±11, with uncertainties in the measurement weaker by 1 order of magnitude than those obtained under the assumption of standard recombination while constraints on the shift parameter are shifted by 1σ to R=1.734±0.028. From the WMAP5 data we obtain the following constraints on the resonance and ionization sources parameters: γα<0.39 and γi<0.058 at 95% c.l.. Although delayed recombination limits the precision of parameter estimation from the WMAP satellite, we demonstrate that this should not be the case for future, smaller angular scales measurements, such as those by the Planck satellite mission.

  19. Head injury.

    PubMed

    Hureibi, K A; McLatchie, G R

    2010-05-01

    Head injury is one of the commonest injuries in sport. Most are mild but some can have serious outcomes. Sports medicine doctors should be able to recognise the clinical features and evaluate athletes with head injury. It is necessary during field assessment to recognise signs and symptoms that help in assessing the severity of injury and making a decision to return-to-play. Prevention of primary head injury should be the aim. This includes protective equipment like helmets and possible rule changes. PMID:20533694

  20. Delayed sequelae of pituitary irradiation.

    PubMed

    Woodruff, K H; Lyman, J T; Lawrence, J H; Tobias, C A; Born, J L; Fabrikant, J I

    1984-01-01

    Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  1. Delayed sequelae of pituitary irradiation

    SciTech Connect

    Woodruff, K.H.; Lyman, J.T.; Lawrence, J.H.; Tobias, C.A.; Born, J.L.; Fabrikant, J.I.

    1984-01-01

    Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal ral tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  2. Bicycling injuries.

    PubMed

    Silberman, Marc R

    2013-01-01

    Bicycling injuries can be classified into bicycle contact, traumatic, and overuse injuries. Despite the popularity of cycling, there are few scientific studies regarding injuries. Epidemiological studies are difficult to compare due to different methodologies and the diverse population of cyclists studied. There are only three studies conducted on top level professionals. Ninety-four percent of professionals in 1 year have experienced at least one overuse injury. Most overuse injuries are mild with limited time off the bike. The most common site of overuse injury is the knee, and the most common site of traumatic injury is the shoulder, with the clavicle having the most common fracture. Many overuse and bicycle contact ailments are relieved with simple bike adjustments.

  3. The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

    PubMed

    MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

    2012-10-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  4. Digital time delay

    DOEpatents

    Martin, A.D.

    1986-05-09

    Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay provides a first output signal at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits latch the high resolution data to form a first synchronizing data set. A selected time interval has been preset to internal counters and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses count down the counters to generate an internal pulse delayed by an internal which is functionally related to the preset time interval. A second LCD corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD to generate a second set of synchronizing data which is complementary with the first set of synchronizing data for presentation to logic circuits. The logic circuits further delay the internal output signal with the internal pulses. The final delayed output signal thereafter enables the output pulse generator to produce the desired output pulse at the preset time delay interval following input of the trigger pulse.

  5. Extensor tendon injuries in athletes.

    PubMed

    Chauhan, Aakash; Jacobs, Bruce; Andoga, Alexandra; Baratz, Mark E

    2014-03-01

    Extensor tendon injuries of the hand and wrist in high-level athletes can cause a delay in return to play and permanently affect their performance. Given the inherent demand for a speedy and complete recovery, orthopedic surgeons must have an understanding of how to best direct an athlete's treatment for these injuries. The extensor anatomy is very intricate and a thorough understanding of the anatomy can help with both diagnosis and treatment. However, untreated or poorly managed injuries are at risk of leading to chronic deformities. We will discuss the diagnosis and management of the most common extensor tendon injuries and tendinopathies of the hand found in athletes: mallet fingers, swan-neck deformities, boutonniere deformities, central slip ruptures, sagittal band ruptures, intersection syndrome, extensor carpi ulnaris tendinitis, and extensor carpi ulnaris subluxation. PMID:24651290

  6. Radiation dermatitis

    SciTech Connect

    Shack, R.B.; Lynch, J.B.

    1987-04-01

    Even in this era of modern radiotherapy, injuries associated with the medical and industrial use of radiation devices will continue to pose a difficult problem for the reconstructive surgeon. It must be borne in mind that the single most serious hazard to surgery in irradiated tissue is the lodgement of bacteria in tissue rendered avascular by the radiation and the secondary necrosis from the infection itself. The basic principles of wound management must be augmented by thorough knowledge of the use of well-vascularized muscle and musculocutaneous flap to provide adequate, blood-rich, soft-tissue coverage.

  7. Blast injury research models

    PubMed Central

    Kirkman, E.; Watts, S.; Cooper, G.

    2011-01-01

    Blast injuries are an increasing problem in both military and civilian practice. Primary blast injury to the lungs (blast lung) is found in a clinically significant proportion of casualties from explosions even in an open environment, and in a high proportion of severely injured casualties following explosions in confined spaces. Blast casualties also commonly suffer secondary and tertiary blast injuries resulting in significant blood loss. The presence of hypoxaemia owing to blast lung complicates the process of fluid resuscitation. Consequently, prolonged hypotensive resuscitation was found to be incompatible with survival after combined blast lung and haemorrhage. This article describes studies addressing new forward resuscitation strategies involving a hybrid blood pressure profile (initially hypotensive followed later by normotensive resuscitation) and the use of supplemental oxygen to increase survival and reduce physiological deterioration during prolonged resuscitation. Surprisingly, hypertonic saline dextran was found to be inferior to normal saline after combined blast injury and haemorrhage. New strategies have therefore been developed to address the needs of blast-injured casualties and are likely to be particularly useful under circumstances of enforced delayed evacuation to surgical care. PMID:21149352

  8. Skiing Injuries

    PubMed Central

    Bartlett, L. H.

    1975-01-01

    In the broad spectrum of orthopedic skiing injuries, ‘second aid’ on the mountain and at the base by the physician is very important. All skiing physicians should carry minimal medical supplies, including narcotic medication. Diagnosis and treatment of injuries at the hospital are outlined. Most ski fractures of the tibia can be treated by conservative methods. A more aggressive approach to diagnosis and treatment of ligamentous injuries of the knee is recommended. PMID:2046