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Sample records for chronic radiation injury

  1. Injury of the blood-testies barrier after low-dose-rate chronic radiation exposure

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    Sohn, Young Hoon; Bae Min Ji; Lee, Chang Geun; Yang, Kwang Mo; Jur, Kyu; Kim, Jong Sun [Dongnam Institute of Radiological and Medical Science, Busan (Korea, Republic of)

    2014-04-15

    The systemic effect of radiation increases in proportionally with the dose and dose rate. Little is known concerning the relationships between harmful effects and accumulated dose, which is derived from continuous low-dose rate radiation exposure. Recent our studies show that low-dose-rate chronic radiation exposure (3.49 mGy/h) causes adverse effects in the testis at a dose of 2 Gy (6 mGy/h). However, the mechanism of the low-dose-rate 2 Gy irradiation induced testicular injury remains unclear. The present results indicate that low-dose rate chronic radiation might affect the BTB permeability, possibly by decreasing levels of ZO-1, Occludin-1, and NPC-2. Furthermore, our results suggest that there is a risk of male infertility through BTB impairment even with low-dose-rate radiation if exposure is continuous.

  2. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG Yong; LI Ming-chun; FU Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation.Methods Animals were divided into three groups (n =10),they were animals exposed to radiation (Rad),normal control animals (Ctr),and irradiated animals treated with LTN (Rad + LTN).Animal model of chronic radiation stress injury was induced by irradiating mice with 60Co γ-ray for 6 weeks from Monday to Friday consecutively.Before radiation,the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL),whereas mice in other groups were injected with 0.9% physiological saline.The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen.The cell numbers and viability of T lymphocytes,which were isolated from the spleen,were determined by Trypan blue staining.Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured.Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes,associated with reduced T lymphocytes viability and functions,and elevated NO production.Treatment with LTN significantly normalized the elevated NO production,and attenuated the negative outcomes resulting from radiation mentioned above.Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  3. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG; Yong; LI; Ming-chun; FU; Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation. Methods Animals were divided into three groups (n = 10), they were animals exposed to radiation (Rad), normal control animals (Ctr), and irradiated animals treated with LTN (Rad + LTN). Animal model of chronic radiation stress injury was induced by irradiating mice with 60 Co γ-ray for 6 weeks from Monday to Friday consecutively. Before radiation, the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL), whereas mice in other groups were injected with 0.9% physiological saline. The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen. The cell numbers and viability of T lymphocytes, which were isolated from the spleen, were determined by Trypan blue staining. Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured. Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes, associated with reduced T lymphocytes viability and functions, and elevated NO production. Treatment with LTN significantly normalized the elevated NO production, and attenuated the negative outcomes resulting from radiation mentioned above. Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  4. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

    Science.gov (United States)

    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

  5. Acute local radiation injuries

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    Gongora, R. (Institut Curie, 75 - Paris (France)); Jammet, H. (Commissariat a l' Energie Atomique, ISPN, 92 - Fontenay-aux-Roses (France))

    1983-01-01

    Local acute radiation injuries do not occur very often. Their origin is generally accidental. They show specific anatomo-clinical features. The clinical evolution and therapeutic behaviour are dependent on the dose level and topographical distribution. The dosimetric assessment requires physical methods and paraclinical investigations. From a study of 60 cases followed by the International Center of Radiopathology, the clinical symptomatology is described and the problems raised to the radiopathologist physician by local acute radiation injuries are stated.

  6. Chronic avulsive injuries of childhood

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    Donnelly, L.F.; Helms, C.A. [Dept. of Radiology, Duke Univ. Medical Center, Durham, NC (United States); Bisset, G.S. III [Dept. of Radiology, Duke Univ. Medical Center, Durham, NC (United States)]|[Department of Pediatrics, Duke University Medical Center, Durham, NC (United States); Squire, D.L. [Department of Pediatrics, Duke University Medical Center, Durham, NC (United States)

    1999-03-01

    Children and adolescents are prone to avulsive injuries related to a combination of their propensity for great strength, ability to sustain extreme levels of activity, and immature growing apophyses. Appropriate interpretation of imaging studies showing chronic avulsive injuries is essential so that the irregularity and periostitis that can be associated with chronic avulsions is not misinterpreted as probable malignancy. This article reviews the chronic avulsive injuries of childhood. (orig.) With 12 figs., 8 refs.

  7. Radiation Injury to the Brain

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    ... Tumors Brain Tumors Brain Disorders AVMs Radiosurgery Gamma Knife Linac Radiotherapy Overview Childhood Brain Tumors IMRT Radiation Therapy Radiation Injury Treatment Day Making a Decision Centers of Excellence Publications Definitions Q & ...

  8. Chronic radiation syndrome

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    Akleyev, Alexander V. [Urals Research Centre for Radiation Medicine, Chelyabinsk (Russian Federation). Clinical Dept.

    2014-04-01

    Comprehensive analysis of chronic radiation syndrome, covering epidemiology, pathogenesis, pathoanatomy, diagnosis and treatment. Based on observations in a unique sample of exposed residents of the Techa riverside villages in the Urals. Casts new light on the condition. Of value for all practitioners and researchers with an interest in chronic radiation syndrome. This book covers all aspects of chronic radiation syndrome (CRS) based on observations in a unique sample of residents of the Techa riverside villages in the southern Urals who were exposed to radioactive contamination in the 1950s owing to releases of liquid radioactive wastes from Mayak Production Association, which produced plutonium for weapons. In total, 940 cases of CRS were diagnosed in this population and these patients were subjected to detailed analysis. The opening chapters address the definition and classification of CRS, epidemiology and pathogenesis, covering molecular and cellular mechanisms, radioadaptation, and the role of tissue reactions. The pathoanatomy of CRS during the development and recovery stages is discussed for all organ systems. Clinical manifestations of CRS at the different stages are then described in detail and the dynamics of hematopoietic changes are thoroughly examined. In the following chapters, principles of diagnosis (including assessment of the exposure doses to critical organs) and differential diagnosis from a wide range of other conditions are discussed and current and potential treatment options, described. The medical and social rehabilitation of persons with CRS is also covered. This book, which casts new light on the condition, will be of value for all practitioners and researchers with an interest in CRS.

  9. Mechanisms of chronic pain from whiplash injury.

    Science.gov (United States)

    Davis, Charles G

    2013-02-01

    This article is to provide insights into the mechanisms underlying chronic pain from whiplash injury. Studies show that injury produces plasticity changes of different neuronal structures that are responsible for amplification of nociception and exaggerated pain responses. There is consistent evidence for hypersensitivity of the central nervous system to sensory stimulation in chronic pain after whiplash injury. Tissue damage, detected or not by the available diagnostic methods, is probably the main determinant of central hypersensitivity. Different mechanisms underlie and co-exist in the chronic whiplash condition. Spinal cord hyperexcitability in patients with chronic pain after whiplash injury can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain pain in the absence of detectable tissue damage. Whiplash is a heterogeneous condition with some individuals showing features suggestive of neuropathic pain. A predominantly neuropathic pain component is related to a higher pain/disability level.

  10. Chronic radiation enteritis and malnutrition.

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    Webb, Gwilym James; Brooke, Rachael; De Silva, Aminda Niroshan

    2013-07-01

    Radiation enteritis is defined as the loss of absorptive capacity of the intestine following irradiation, which is most commonly seen after radiotherapy for pelvic and abdominal malignancies. It is divided into acute and chronic forms and usually presents with diarrhea and malabsorption. Malnutrition is a common complication of chronic radiation enteritis (CRE). We reviewed the etiology, prevalence, symptoms, diagnosis and management of CRE and CRE with malnutrition in this article. Functional short bowel syndrome as a cause of malnutrition in CRE is also considered. The diagnostic work-up includes serum markers, endoscopy, cross-sectional imaging and the exclusion of alternative diagnoses such as recurrent malignancy. Management options of CRE include dietary manipulation, anti-motility agents, electrolyte correction, probiotics, parenteral nutrition, surgical resection and small bowel transplantation. Treatment may also be required for coexisting conditions including vitamin B12 deficiency, bile acid malabsorption and depression.

  11. Rabbit model of radiation-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Zhen-Zong Du; Hua Ren; Jian-Fei Song; Li-Fei Zhang; Feng Lin; Hai-Yong Wang

    2013-01-01

    Objective:To explore the feasibility of establishing an animal model of chronic radiation-induced lung injury.Methods:Twenty-eightNewZealand white rabbits were randomly divided into3 groups(the right lung irradiation group, the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established by high-does radiotherapy in the irradiation groups, then all rabbits underwentCT and pathological examinations at1,2,4,8,12,16 weeks, respectively after radiation.Results:Within4 weeks of irradiation, some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At8-12 weeks after irradiation,CT scanning showed ground glass samples signs, patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

  12. Hypoaminoacidemia Characterizes Chronic Traumatic Brain Injury.

    Science.gov (United States)

    Durham, William J; Foreman, Jack P; Randolph, Kathleen M; Danesi, Christopher P; Spratt, Heidi; Masel, Brian D; Summons, Jennifer R; Singh, Charan K; Morrison, Melissa; Robles, Claudia; Wolfram, Cindy; Kreber, Lisa A; Urban, Randall J; Sheffield-Moore, Melinda; Masel, Brent E

    2017-01-15

    Individuals with a history of traumatic brain injury (TBI) are at increased risk for a number of disorders, including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. However, mediators of the long-term morbidity are uncertain. We conducted a multi-site, prospective trial in chronic TBI patients (∼18 years post-TBI) living in long-term 24-h care environments and local controls without a history of head injury. Inability to give informed consent was exclusionary for participation. A total of 41 individuals (17 moderate-severe TBI, 24 controls) were studied before and after consumption of a standardized breakfast to determine if concentrations of amino acids, cytokines, C-reactive protein, and insulin are potential mediators of long-term TBI morbidity. Analyte concentrations were measured in serum drawn before (fasting) and 1 h after meal consumption. Mean ages were 44 ± 15 and 49 ± 11 years for controls and chronic TBI patients, respectively. Chronic TBI patients had significantly lower circulating concentrations of numerous individual amino acids, as well as essential amino acids (p = 0.03) and large neutral amino acids (p = 0.003) considered as groups, and displayed fundamentally altered cytokine-amino acid relationships. Many years after injury, TBI patients exhibit abnormal metabolic responses and altered relationships between circulating amino acids, cytokines, and hormones. This pattern is consistent with TBI, inducing a chronic disease state in patients. Understanding the mechanisms causing the chronic disease state could lead to new treatments for its prevention.

  13. Computational Biology: Modeling Chronic Renal Allograft Injury.

    Science.gov (United States)

    Stegall, Mark D; Borrows, Richard

    2015-01-01

    New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical and experimental data and how we plan to expand this approach to investigate specific mechanisms of chronic renal allograft injury.

  14. Surgical treatment of intestinal radiation injury

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    Maekelae, J.Ne.; Nevasaari, K.; Kairaluoma, M.I.

    1987-10-01

    A review of 43 consecutive patients requiring operation for serious intestinal radiation injury was undertaken to elucidate the efficacy of surgical treatment. The most common site of radiation injury was the rectum (19 cases), followed by the small bowel (13 cases), the colon (7 cases), and the combination of these (4 cases). The overall operative mortality was 14%; morbidity, 47%; and the postoperative symptom-free period, 18 +/- 30 months. Colostomy (N = 20) carried the lowest risk of mortality, 0%, as compared with resection (N = 17) and bypass procedure (N = 6), which were accompanied by the mortalities of 24% and 33%, respectively. During the follow-up (3-13 years) 12 patients (28%) died of recurrent cancer and 9 patients (21%) of persistent radiation injury, which yielded an overall mortality of 65% after resection and 50% and 65% after bypass and colostomy procedures, respectively. Continuing radiation damage led to 15 late reoperations. Ten of these were performed after colostomy, four after resection, and one after bypass. We conclude that colostomy cannot be regarded as a preferred operative method, because it does not prevent the progression of radiation injury and because it is, for this reason, associated with a higher late-complication rate. A more radical surgery is recommended but with the limitation that the operative method must be adapted to the operative finding.

  15. Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept (Radiation Injury Algorithms)

    Science.gov (United States)

    2014-01-01

    Category three or RC3) in a Rhesus monkey total- body irradiation (TBI) model. Multivariate Radiation Injury Estimation algorithms were formulated for...multivariate algorithm for calculating the appropriate RC severity for H-ARS with a Rhesus monkey TBI model using a 6.5 Gy dose, which based on the...Correspondence should be addressed to David L. Bolduc, Ph.D.; david.bolduc@usuhs.edu Running title. Radiation Injury Algorithms Key terms

  16. Behavioral endpoints for radiation injury

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    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.

  17. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    Michael eRobbins

    2012-07-01

    Full Text Available 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

  18. Chronic Traumatic Brain Injury in Amateur Boxers

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    M. Rahmati

    2008-04-01

    Full Text Available Introduction & objective: Despite of young and adolescence intent to the boxing sport, because of dominant aggression and direct blows contact to head, face and central nervous system, it is continuously criticize by different groups. The groups of sporting and physician conventions are distinguished boxing with physical and neuropsychological disorders and some groups believe that side effects of this sport are not more than other sports. For this base the aim of this study was to determine the chronic traumatic brain injury in a group amateur boxers.Materials & Methods: In a case-control study, three groups of sport men were considered, each group contained 20 randomly selected cases. The first group were amateur boxers with 4 years minimal activity(directly has been presented to the head blows, second group were amateur soccer players with 4 years minimal activity(has been presented to the not very severe head blows, third group were non athlete subjects .The groups were matched in weight, height, age and education .To understand brain disorder interview by medicine method has been used, then Wiskancin, Bonardele, Bender geshtalt, Kim karad visual memory, Benton and wechler memory (Alef type tests has been performed and EEG has got in the same hour and condition.Results: The homogeneity of between group variances was gained by the statistical method. Also between structural–visual abilities neuropsychological aspect in groups, significant difference has been gained (p= 0.000. In Kim karad visual memory test at the mild and long term visual memory deficit, significant differences between three groups was observed (P= 0.000, P=0.009 that least score has been belonged to the boxers. Also in boxers 6 abnormal EEGs is observed.Conclusion: It can be said that of four years amateur boxing can affect on boxers visual and memory perception and their spatial orientation. Additionally our study have showed that amateur boxing has a significant

  19. Endoscopic management of chronic radiation proctitis.

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    Rustagi, Tarun; Mashimo, Hiroshi

    2011-11-01

    Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications. This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis.

  20. Endoscopic management of chronic radiation proctitis

    Institute of Scientific and Technical Information of China (English)

    Tarun Rustagi; Hiroshi Mashimo

    2011-01-01

    Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications.This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis.

  1. Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

    Science.gov (United States)

    2015-10-01

    central sensitization to nociceptive stimuli culminates in profound debilitating pain that serves no adaptive purpose for the sufferer. It is now...Award Number: W81XWH-11-1-0806 TITLE: Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment...29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0806 Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time

  2. Reduction of radiation injury of fresh agricultural products by saccharide

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    Hayashi, Toru; Todoroki, Setsuko [National Food Research Inst., Tsukuba, Ibaraki (Japan)

    1998-02-01

    To establish irradiation technologies as one of alternative technology of methyl bromide fumigation, radiation sensitivities for each kind of fresh agricultural products and reduction of radiation injury were investigated. Fresh vegetables and flowers such as cabbage, sprouts, asparagus, lettuce, chrysanthemum, carnation, rose, etc. were used and irradiated with 750 Gy {gamma}-ray. Flowers received radiation injury were soaked into various kinds of solutions for one night, then they were irradiated with 500 Gy {gamma}-ray. They showed different radiation sensitivities. Cruciferae plant showed radioresistance and Compositae plant radiosensitivity. A keeping quality agent for cut flowers indicated protection effect on radiation injury. (S.Y.)

  3. Studies of acute and chronic radiation injury at the Biological and Medical Research Division, Argonne National Laboratory, 1970-1992: The JANUS Program Survival and Pathology Data

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    Grahn, D.; Wright, B.J.; Carnes, B.A.; Williamson, F.S.; Fox, C.

    1995-02-01

    A research reactor for exclusive use in experimental radiobiology was designed and built at Argonne National Laboratory in the 1960`s. It was located in a special addition to Building 202, which housed the Division of Biological and Medical Research. Its location assured easy access for all users to the animal facilities, and it was also near the existing gamma-irradiation facilities. The water-cooled, heterogeneous 200-kW(th) reactor, named JANUS, became the focal point for a range of radiobiological studies gathered under the rubic of {open_quotes}the JANUS program{close_quotes}. The program ran from about 1969 to 1992 and included research at all levels of biological organization, from subcellular to organism. More than a dozen moderate- to large-scale studies with the B6CF{sub 1} mouse were carried out; these focused on the late effects of whole-body exposure to gamma rays or fission neutrons, in matching exposure regimes. In broad terms, these studies collected data on survival and on the pathology observed at death. A deliberate effort was made to establish the cause of death. This archieve describes these late-effects studies and their general findings. The database includes exposure parameters, time of death, and the gross pathology and histopathology in codified form. A series of appendices describes all pathology procedures and codes, treatment or irradiation codes, and the manner in which the data can be accessed in the ORACLE database management system. A series of tables also presents summaries of the individual experiments in terms of radiation quality, sample sizes at entry, mean survival times by sex, and number of gross pathology and histopathology records.

  4. The anatomy and biomechanics of acute and chronic whiplash injury.

    Science.gov (United States)

    Siegmund, Gunter P; Winkelstein, Beth A; Ivancic, Paul C; Svensson, Mats Y; Vasavada, Anita

    2009-04-01

    Whiplash injury is the most common motor vehicle injury, yet it is also one of the most poorly understood. Here we examine the evidence supporting an organic basis for acute and chronic whiplash injuries and review the anatomical sites within the neck that are potentially injured during these collisions. For each proposed anatomical site--facet joints, spinal ligaments, intervertebral discs, vertebral arteries, dorsal root ganglia, and neck muscles--we present the clinical evidence supporting that injury site, its relevant anatomy, the mechanism of and tolerance to injury, and the future research needed to determine whether that site is responsible for some whiplash injuries. This article serves as a snapshot of the current state of whiplash biomechanics research and provides a roadmap for future research to better understand and ultimately prevent whiplash injuries.

  5. Integrative Metabolic Signatures for Hepatic Radiation Injury.

    Directory of Open Access Journals (Sweden)

    Irwin Jack Kurland

    Full Text Available 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.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.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.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.

  6. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury.

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    Hay, Jennifer; Johnson, Victoria E; Smith, Douglas H; Stewart, William

    2016-05-23

    Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article.

  7. Radiation Combined Injury: DNA Damage, Apoptosis, and Autophagy

    Science.gov (United States)

    2010-01-01

    the course of their disease (5) represents another significant source of exposure as normal tissues are subjected to radiation injury. Those charged...received thermal burns concurrent with radiation injury, (26, 35). At the Chernobyl reactor meltdown, 10% of 237 victims exposed to radiation received...injections, orally administered drugs, and perhaps subcutaneous injections (39) may be the most complex treatments available to mass casualty victims

  8. Histomorphologic change of radiation pneumonitis in rat lungs: captopril reduces rat lung injury induced by irradiation

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    Kim, Jin Hee [College of Medicine, Keimhyung Univ., Taegu (Korea, Republic of)

    1999-09-01

    To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-{alpha} and TGF {beta} and rat lung damage by radiation and captopril. Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group expression of TNF-{alpha} and TGF-{beta}] increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF- P increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation

  9. Chronic haemorrhagic radiation proctitis: A review

    Institute of Scientific and Technical Information of China (English)

    Vishnu Prasad Nelamangala Ramakrishnaiah; Srinivasan Krishnamachari

    2016-01-01

    Chronic haemorrhagic radiation proctitis(CHRP) is a difficult problem faced by the patients following radiation for pelvic malignancy. There is no standardtreatment for this condition, but many methods of treatment are available. The aim of this study was to review the literature to see whether there is an improvement in the available evidence in comparison with previously published systematic reviews in treating patients with CHRP. The Pub Med/Medline database and Google Scholar search was selectively searched. Studies, which treated patients with rectal bleeding due to chronic radiation proctitis or CHRP, were included. Seventy studies were finally selected out of which 14 were randomized controlled clinical trials. Though these studies could not be compared, it could be seen that there was an improvement in the methodology of the studies. There was an objective assessment of symptoms, signs and an objective assessment of outcomes. But, still, there were only a few studies that looked into the quality of life following treatment of CHRP. To increase recruitment to trials, a national registry of cases with established late radiation toxicity would facilitate the further improvement of such studies. Some of the conclusions that could be reached based on the available evidence are 4% formalin should be the first line treatment for patients with CHRP. Formalin and argon plasma coagulation(APC) are equally effective, but formalin is better for severe disease. Refractory patients, not responding to formalin or APC, need to be referred for hyperbaric oxygen therapy or surgery. Radio-frequency ablation is a promising modality that needs to be studied further in randomized trials.

  10. Radiation resistance and injury of Yersinia enterocolitica

    Energy Technology Data Exchange (ETDEWEB)

    El-Zawahry, Y.A.; Rowley, D.B.

    1979-01-01

    The D values of Yersinia enterocolitica strains IP134, IP107, and WA, irradiated at 25/sup 0/C in Trypticase soy broth, ranged from 9.7 to 11.8 krad. When irradiated in ground beef at 25 and -30/sup 0/C, the D value of strain IP107 and 19.5 and 38.8 krad, respectively. Cells suspended in Trypticase soy broth were more sensitive to storage at -20/sup 0/C than those mixed in ground beef. The percentages of inactivation and of injury (inability to form colonies in the presence of 3.0% NaCl) of cells stored in ground beef for 10 days at -20/sup 0/C were 70 and 23%, respectively. Prior irradiation did not alter the cell's sensitivity to storage at -20/sup 0/C, nor did storage at -20/sup 0/C alter the cell's resistance to irradiation at 25/sup 0/C. Added NaCl concentrations of up to 4.0% in Trypticase soy agar (TSA) (which contains 0.5% NaCl) had little effect on colony formation at 36/sup 0/C of unirradiated Y. enterocolitica. With added 4.0% NaCl, 79% of the cells formed colonies at 36/sup 0/C; with 5.0% NaCl added, no colonies were formed. Although 2.5% NaCl added to ground beef did not sensitize Y. enterocolitica cells to irradiation, when added to TSA it reduced the number of apparent radiation survivors. Cells uninjured by irradiation formed colonies on TSA when incubated at either 36 or 5/sup 0/C. More survivors of an exposure to 60 krad were capable of recovery and forming colonies on TSA when incubated at 36/sup 0/C for 1 day than at 5/sup 0/C for 14 days. This difference in count was considered a manifestation of injury to certain survivors of irradiation.

  11. Ninety-nine years of radiation injuries in dental radiography

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Kadzuo (Nippon Dental Univ., Niigata (Japan). School of Dentistry at Niigata)

    1994-06-01

    A German dentist, F.O. Walkhoff, has started dental radiography as early as two weeks after Roentgen's discovery on November 8, 1895. The purpose of this paper is to revisit radiation injuries by dividing the era into the era of Kells (before World War II) and the era of low exposure doses (after World War II). Edmund Kells (1856-1928), a pioneer of dental radiologist in the United States, has later become a victim of radiation injuries. During the era of Kells, skin radiation injuries were frequent among the group of dental and medical personnels. In the era of low exposure doses, cancers, leukemia, and genetic effects have begun to receive attention. Radiation injuries occurring in a dental practice are discussed in the context of the two eras. (N.K.) 43 refs.

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

    Science.gov (United States)

    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

  13. Peripheral nervous system involvement in chronic spinal cord injury

    DEFF Research Database (Denmark)

    Tankisi, Hatice; Pugdahl, Kirsten; Rasmussen, Mikkel Mylius

    2015-01-01

    Introduction: Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). Methods: Twelve subjects with chronic low cervical or thoracic SCI were included...

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

    Science.gov (United States)

    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

  15. The paradox of chronic neuroinflammation, systemic immune suppression and autoimmunity after traumatic chronic spinal cord injury

    OpenAIRE

    Schwab, Jan M.; Zhang, Yi; Kopp, Marcel A; Brommer, Benedikt; Popovich, Phillip G.

    2014-01-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the “immune privileged/specialized” milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of “SCI disease” ...

  16. Chronic radiation-induced dermatitis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Spałek M

    2016-12-01

    Full Text Available Mateusz Spałek Department of Radiotherapy I, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Abstract: Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF. RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and

  17. Management of radiation injuries of 10 cases of gastrointestinal tracts

    Energy Technology Data Exchange (ETDEWEB)

    Tomida, Takashi; Yano, Takashi; Hidaka, Naoaki; Okada, Yoshikatsu; Iwasaki, Makoto; Goshima, Hiromichi

    1984-11-01

    Ten cases of delayed radiation injuries of the gastrointestinal tracts (consisting of 2 with peptic ulcer, 4 with intestinal obstruction, and 4 with rectal bleeding) are reported. Although conservative therapy or artificial colostomy was undertaken in all cases, satisfactory results were not obtained. In four cases in which subsequent resection of the gastrointestinal tracts was performed, the prognosis was favorable, but various symptoms still continued in the other non-resected cases. Delayed radiation injuries are progressive lesions involving the vasculo-connective tissue, so that cure can not be achieved. Resection of the damaged gastrointestinal tract is recommended, however, this is difficult to do in many cases. (Namekawa, K.).

  18. The characteristics of chronic central pain after traumatic brain injury.

    Science.gov (United States)

    Ofek, Hadas; Defrin, Ruth

    2007-10-01

    Central pain following traumatic brain injury (TBI) has not been studied in depth. Our purpose was to conduct a systematic study of patients with TBI suffering from chronic central pain, and to describe the characteristics of the central pain. Groups were TBI patients with (TBIP) and without central pain (TBINP) and healthy controls. TBI patients with other pain mechanisms were excluded from the study. Participants underwent quantitative somatosensory testing in the painful and pain-free body regions. Thresholds for warmth, cold, heat-pain, touch and graphesthesia were measured and pathologically evoked pain (allodynia, hyperpathia and wind-up pain) evaluated. Chronic pain was mapped and characterized. Chronic pain developed at a relatively late onset (6.6+/-9 months) was almost exclusively unilateral and reported as pricking, throbbing and burning. Although both TBIP and TBINP exhibited a significant reduction in thermal and tactile sensations compared to controls, thermal sensations in the painful regions of TBIP were significantly more impaired than pain-free regions in the same patients (p<0.01) and in TBINP (p<0.01). Painful regions also exhibited very high rates of allodynia, hyperpathia and exaggerated wind-up. The characteristics of the chronic pain resembled those of other central pain patients although TBIP displayed several unique features. The sensory profile indicated that damage to the pain and temperature systems is a necessary but not sufficient condition for the development of chronic central pain following TBI. Neuronal hyperexcitability may be a contributing factor to the chronic pain.

  19. Postconcussion Symptoms in Patients with Injury-Related Chronic Pain

    Directory of Open Access Journals (Sweden)

    Britt Marie Stålnacke

    2012-01-01

    Full Text Available Background. Postconcussion symptoms (PCSs—such as fatigue, headache, irritability, dizziness, and impaired memory—are commonly reported in patients who have mild traumatic brain injuries (MTBIs. Evaluation of PCS after MTBI is proposed to have a diagnostic value although it is unclear whether PCS are specific to MTBI. After whiplash injuries, patients most often complain of headaches and neck pain; the other PCS are not as closely evaluated. In patients with chronic pain because of other injuries, the presence of PCS is unclear. This study aimed to describe the frequency of PCS in patients with injury-related pain and to examine the relationships between PCS, pain, and psychological factors. Methods. This study collected data using questionnaires addressing PCS (Rivermead Postconcussion Questionnaire, RPQ, pain intensity (Visual Analogue Scale, depression, anxiety (Hospital, Anxiety, and Depression Scale, and posttraumatic stress (Impact of Event Scale. Results. Fatigue (90.7%, sleep disturbance (84.9%, headache (73.5%, poor concentration (88.2%, and poor memory (67.1% were some of the most commonly reported PCS. Significant relationships were found between PCS and posttraumatic stress, depression, and anxiety. Conclusion. To optimize treatment, it is important to assess each patient’s PCS, the mechanism of injury, and factors such as posttraumatic stress and depression.

  20. Antioxidant mechanisms in radiation injury and radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Melatonin as Protection Against Radiation Injury

    DEFF Research Database (Denmark)

    Zetner, D; Andersen, L P H; Rosenberg, J

    2016-01-01

    -hormone melatonin is a free radical scavenger, and induces several anti-oxidative enzymes. This review investigates the scientific literature on the protective effects of melatonin against exposure to ionizing radiation, and discusses the clinical potential of melatonin as prophylactic treatment against ionizing...... radiation damage. Methods: A systematic literature search was performed and included experimental or clinical studies written in English that investigated the protective effects of melatonin against gamma or X-ray irradiation in vivo. Studies were excluded if patients were treated with chemotherapy...... concomitantly. Results: 37 studies were included in the review. All were of experimental case-control design and employed animals. The studies demonstrated that exogenous melatonin reduced oxidative stress and inflammation in all investigated tissues. Furthermore, melatonin increased 30-day survival...

  2. Chronic post-traumatic headache after mild head injury

    DEFF Research Database (Denmark)

    Kjeldgaard, Dorte; Forchhammer, Hysse; Teasdale, Tom

    2014-01-01

    to or above the cut-off score for having post-traumatic stress disorder (PTSD) according to the HTQ. In terms of demographics and headache, the groups were comparable except the CPTH group were more often without affiliation to the labour market ( P ...BACKGROUND: The aetiology behind chronic post-traumatic headache (CPTH) after mild head injury is unclear and management is complicated. In order to optimize treatment strategies we aimed to characterize a CPTH population. METHODS: Ninety patients with CPTH and 45 patients with chronic primary...... headaches were enrolled from the Danish Headache Center. All patients were interviewed about demographic and headache data. They completed the Harvard Trauma Questionnaire (HTQ), Rivermead Post Concussion Symptoms Questionnaire, SF-36 and a headache diary. RESULTS: The CPTH group experienced more cognitive...

  3. Incidence and predictors of chronic headache attributed to whiplash injury.

    Science.gov (United States)

    Obermann, M; Nebel, K; Riegel, A; Thiemann, D; Yoon, M-S; Keidel, M; Stude, P; Diener, Hc; Katsarava, Z

    2010-05-01

    We identified clinical, demographic and psychological predictive factors that may contribute to the development of chronic headache associated with mild to moderate whiplash injury [Quebec Task Force (QTF) ≤ II] and determined the incidence of this chronic pain state. Patients were recruited prospectively from six participating accident and emergency departments. While 4.6% of patients developed chronic headache attributed to whiplash injury according to the International Classification of Headache Disorders, 2nd edn criteria, 15.2% of patients complained about headache lasting > 42 days (QTF criteria). Predictive factors were pre-existing facial pain [odds ratio (OR) 9.7, 95% confidence interval (CI) 2.1, 10.4; P = 0.017], lack of confidence to recover completely (OR 5.5, 95% CI 2.0, 13.2; P = 0.005), sore throat (OR 5.0, 95% CI 1.5, 8.9; P = 0.013), medication overuse (OR 4.2, 95% CI 1.4, 12.3; P = 0.009), high Neck Disability Index (OR 4.0, 95% CI 1.3, 12.6; P = 0.019), hopelessness/anxiety (OR 3.8, 95% CI 1.3, 8.7; P = 0.024), and depression (OR 3.3, 95% CI 1.2, 9.4; P = 0.024). The lack of a control group limits the conclusions that can be drawn from this study. Identified predictors closely resemble those found in chronic primary headache disorders.

  4. Radiological and Nuclear Emergencies: Medical Management of Radiation Injuries

    Directory of Open Access Journals (Sweden)

    L. Ravi Shankar

    2011-02-01

    Full Text Available Nuclear radiation which could be in the form of alpha, beta, gamma rays, etc, could cause radioactive contamination, radiation burns, acute radiation syndrome or a combination of any of these above-mentioned disasters. Effects of radiation and the subsequent treatment depend on the severity of exposure and the organs directly involved. Radiation levels up to 200 rads lead to nausea and vomiting whilst radiation levels between 200 rads and 400 rads lead to diarrhea, vomiting and pneumonitis. Whilst 450 rads is lethal in 50 per cent population, doses above this cause increased fatality and organ involvement with the Central Nervous System being affected with 2000 rads radiation. Nuclear disaster management lies most importantly in identifying that patient who would recover if treated immediately. Whereas decontamination of skin and wounds is done first, immediate first aid may take priority in a seriously injured patient. In the event of internal contamination, effective decorporation maybe required. This is followed by prevention and treatment of infections in sterile conditions. Radiation burn injuries will require effective long-term management. Finally, what would be most important is the necessity to have suitable hospital care where bone marrow, stem cell transfusion and restitution of the immune system would take place.Defence Science Journal, 2011, 61(2, pp.113-117, DOI:http://dx.doi.org/10.14429/dsj.61.830

  5. Chronic neuroendocrinological sequelae of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sklar, C.A. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Constine, L.S. [Univ. of Rochester Medical Center, Rochester, NY (United States)

    1995-03-30

    A variety of neuroendocrine disturbances are observed following treatment with external radiation therapy when the hypothalamic-pituitary axis (HPA) is included in the treatment field. Radiation-induced abnormalities are generally dose dependent and may develop many years after irradiation. Growth hormone deficiency and premature sexual development can occur following doses as low as 18 Gy fractionated radiation and are the most common neuroendocrine problems noted in children. Deficiency of gonadotropins, thyroid stimulating hormone, and adrenocorticotropin are seen primarily in individuals treated with > 40 Gy HPA irradiation. Hyperprolactinemia can be seen following high-dose radiotherapy (>40 Gy), especially among young women. Most neuroendocrine disturbances that develop as a result of HPA irradiation are treatable; patients at risk require long-term endocrine follow-up. 23 refs., 6 figs., 2 tabs.

  6. Experimental model of cutaneous radiation injury in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Meirelles, Rafael Panisi de Campos [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina; Hochman, Bernardo [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. de Cirurgia; Helene Junior, Americo; Fraga, Murillo Francisco Pires [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Dept. de Cirurgia. Divisao de Cirurgia Plastica; Lellis, Rute [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Divisao de Patologia; Ferreira, Lydia Masako, E-mail: rpcmeirelles@yahoo.com.br, E-mail: lydia.dcir@epm.br [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Mediciana. Divisao de Cirugia Plastica

    2013-07-01

    Purpose: to describe an experimental model of cutaneous radiation injury in rabbits. Methods: on this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: after 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 2000 cGy had a 60-day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the 3000cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. One of the animals from group 4500 cGy died on the 7th day with visceral necrosis. The other from the same group had total skin necrosis. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was observed. Conclusion: The proposed experimental model is reproducible. This study suggests that the dosage 4500cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits. (author)

  7. Clinical and dosimetric factors of radiation-induced esophageal injury: Radiation-induced esophageal toxicity

    Institute of Scientific and Technical Information of China (English)

    Wen-Bo Qiao; Yan-Hui Zhao; Yan-Bin Zhao; Rui-Zhi Wang

    2005-01-01

    AIM: To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during threedimensional conformal radiotherapy (3D-CRT). METHODS: We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria.RESULTS: Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, nograde 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P= 0.0001<0.01).CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

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

    Science.gov (United States)

    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.

  9. Expertise of radiation injuries in the GDR and examples of gynecological contact therapy

    Energy Technology Data Exchange (ETDEWEB)

    Arndt, D. (Staatliches Amt fuer Atomsicherheit und Strahlenschutz, Berlin (German Democratic Republic)); Lenz, U. (Betriebspoliklinik des Kombinats Elektro-Apparate-Werke Berlin-Treptow (German Democratic Republic)); Matschke, S. (Akademie der Wissenschaften der DDR, Berlin. Zentralinstitut fuer Krebsforschung); Schmidt, H. (Akademie der Wissenschaften der DDR, Leipzig. Zentralinstitut fuer Isotopen- und Strahlenforschung); Thormann, T. (Humboldt-Universitaet, Berlin (German Democratic Republic). Bereich Medizin (Charite))

    Expertise in cases of radiation injuries is given in the GDR by different institutions depending on etiological factors. Occupational diseases due to ionizing radiation are judged by the National Board of Nuclear Safety and Radiation Protection of the GDR while radiation injuries in medicine are dealt with by institutions for Medical Expertise. Details of organization and procedure of expertise are described as well as cooperation between the institutions mentioned. Two cases of iatrogenic radiation injuries in gynecological intracavitary contact therapy are dealt with and conclusions are drawn for future measures in guaranteeing full radiation protection.

  10. Coniferyl Aldehyde Ameliorates Radiation Intestine Injury via Endothelial Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ye Ji; Jung, Myung Gu; Lee, Yoonjin; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yunsil [Ewha Woman' s Univ., Seoul (Korea, Republic of); Ko, Younggyu [Korea Univ., Seoul (Korea, Republic of)

    2014-05-15

    Cancer treatments related gastrointestinal toxicity has also been recognized as a significant economic burden. Especially, extensive apoptosis of microvascular endothelial cell of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Coniferyl aldehyde (CA) is phenolic compounds isolated from cork stoppers, and one of the major pyrolysis products of lignin. Shi H. was support for the empirical use of CA as a medicinal food for cardiovascular diseases. CA has positive effect in broad way but there is no consequence in radiation induced intestine damage. Here, we investigate effect of CA on small intestine after abdominal IR to mice in this study. In this study, CA increased the survival rate in C3H mice against 13.5 Gy abdominal IR. We found CA protects small intestine via preventing endothelial cell apoptosis and enhancing their angiogenic activity. CA also showed protective effect on crypt cell survival. Endothelial cell survival may affect crypt cell protection against IR. From this data, we concluded that CA is effective for protection against abdominal radiation injury. CA could ameliorate side-effect of radiation therapy.

  11. The investigation of radiation enteritis, especially ileum injuries treated surgically

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Masanari; Watanabe, Satoshi; Honda, Ichiro; Yamamoto, Hiroshi; Yano, Yoshimasa; Hatano, Kazuo [Chiba Cancer Center Hospital (Japan)

    2000-01-01

    Radiation therapy has been widely used as one of several therapies for malignant disease of the lower abdomen. However, radiation enteritis was a severe side effect, and it was very difficult to treat and care. We report the cases of radiation enteritis that we encountered, especially ileum injuries. There were 27 regions in 23 patients: 10 obstipation, 8 fistula 6 perforation, 2 obstipation and perforation, 1 obstipation and fistula to urinary tract, and 1 perforation and bleeding of sigmoid colon. We treated these by combined bypass, resection of the bowels, external fistula, and others. Radiation enteritis is considered a progressive and irreversible disease, and many patients would experience recurrences over their lifetime, and in some cases would need multiple operations. The leakage and the short bowel after resection were severe problems, and in addition, we found that the abdominal wall was one of the difficult problems to treat and care, such as many external fistula and hardening of abdominal wall after polysurgery and radiation therapy. (author)

  12. Neurotherapy for chronic headache following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    David V Nelson; Mary Lee Esty

    2015-01-01

    Background:Chronic headache following traumatic brain injury (TBI) sustained in military service, while common, is highly challenging to treat with existing pharmacologic and non-pharmacologic interventions, and it may be complicated by co-morbid posttraumatic stress. Recently, a novel form of brainwave-based intervention known as the Flexyx Neurotherapy System (FNS), which involves minute pulses of electromagnetic energy stimulation of brainwave activity, has been suggested as a means to address symptoms of TBI. This study reports on a clinical series of patients with chronic headache following service-connected TBI treated with FNS. Methods: Nine veterans of the wars in Afghanistan and Iraq with moderate to severe chronic headaches following service-connected TBI complicated by posttraumatic stress symptoms were treated in 20 individual FNS sessions at the Brain Wellness and Biofeedback Center of Washington (in Bethesda, Maryland, USA). They periodically completed measures including the Brief Pain Inventory-Headache (BPI-HA), previous week worst and average pain ratings, the Posttraumatic Stress Disorder Checklist-Military version (PCL-M), and an individual treatment session numerical rating scale (NRS) for the degree of cognitive dysfunction. Data analyses included beginning-to-end of treatmentt-test comparisons for the BPI-HA, PCL-M, and cognitive dysfunction NRS. Results: All beginning-to-end of treatmentt-test comparisons for the BPI-HA, PCL-M, and cognitive dysfunction NRS indicated statistically significant decreases. All but one participant experienced a reduction in headaches along with reductions in posttraumatic stress and perceived cognitive dysfunction, with a subset experiencing the virtual elimination of headaches. One participant obtained modest headache relief but no improvements in posttraumatic stress or cognitive dysfunction. Conclusions: FNS may be a potentially efficacious treatment for chronic posttraumatic headache sustained in military

  13. Effect of Teriparatide, Vibration and the Combination on Bone Mass and Bone Architecture in Chronic Spinal Cord Injury

    Science.gov (United States)

    2014-10-01

    Spinal Cord Injury Effect of Teriparatide, Vibration and the Combination on Bone Mass and Bone Architechture in Chronic... Spinal Cord Injury 5a. CONTRACT NUMBER W81XWH-10-1-0951 Mass and Bone Architecture in Chronic Spinal Cord Injury 5b. GRANT NUMBER 5c. PROGRAM...distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Severe bone loss commonly occurs in individuals with chronic spinal cord injury who are

  14. Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-12-2-0109 TITLE: Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury...2014-29 Sept 2015 4. TITLE AND SUBTITLE Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain 5a. CONTRACT NUMBER W81XWH-12-2-0109...study is to evaluate the efficacy of a telephone-delivered cognitive behavioral treatment (T-CBT) in Veterans with a history of traumatic brain injury

  15. [Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?].

    Science.gov (United States)

    Piskunov, A K; Nikitin, K V; Potapov, A A

    2015-01-01

    Investigation of the mechanisms of radiation-induced brain injury is a relevant fundamental objective of radiobiology and neuroradiology. Damage to the healthy brain tissue is the key factor limiting the application of radiation therapy in patients with nervous systems neoplasms. Furthermore, postradiation brain injury can be clinically indiscernible from continued tumor growth and requires differential diagnosis. Thus, there exists high demand for biomarkers of radiation effects on the brain in neurosurgery and radiobiology. These markers could be used for better understanding and quantifying the effects of ionizing radiation on brain tissues, as well as for elaborating personalized therapy. Despite the high demand, biomarkers of radiation-induced brain injury have not been identified thus far. The cellular and molecular mechanisms of the effect of ionizing radiation on the brain were analyzed in this review in order to identify potential biomarkers of radiation-induced injury to nervous tissue.

  16. Apoptotic cell death as a target for the treatment of acute and chronic liver injury

    NARCIS (Netherlands)

    Schoemaker, Marieke Henriëtte

    2004-01-01

    Acute liver failure can develop as a consequence of viral hepatitis, drug- or toxin-induced toxicity or rejection after liver transplantation, whereas chronic liver injury can be due to long-term exposure to alcohol, chemicals, chronic viral hepatitis, metabolic or cholestatic disorders. During acut

  17. Acute kidney injury in acute on chronic liver failure.

    Science.gov (United States)

    Maiwall, Rakhi; Sarin, S K; Moreau, Richard

    2016-03-01

    Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.

  18. Family needs in the chronic phase after severe brain injury in Denmark

    DEFF Research Database (Denmark)

    Doser, Karoline; Norup, Anne

    2014-01-01

    Abstract Objective: This preliminary study aimed at investigating (1) changes in the status of family members between time of injury and follow-up in the chronic phase and (2) the most important needs within the family in the chronic phase and whether the needs were perceived as met. Participants......: The sample comprised 42 relatives (76% female, mean age = 53 years) of patients with severe brain injury, who had received intensive sub-acute rehabilitation. The relatives were contacted in the chronic phase after brain injury. Outcome measure: A set of questions about demographics and time spent caregiving...... for the patient was completed. The relatives completed the revised version of the Family Needs Questionnaire, a questionnaire consisting of 37 items related to different needs following brain injury. Results: Significant changes in status were found in employment (z = -3.464, p = 0.001) and co-habitation (z = -3...

  19. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Science.gov (United States)

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

    The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of

  20. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  1. Studies of acute and chronic radiation injury at the Biological and Medical Research Division, Argonne National Laboratory, 1953-1970: Description of individual studies, data files, codes, and summaries of significant findings

    Energy Technology Data Exchange (ETDEWEB)

    Grahn, D.; Fox, C.; Wright, B.J.; Carnes, B.A.

    1994-05-01

    Between 1953 and 1970, studies on the long-term effects of external x-ray and {gamma} irradiation on inbred and hybrid mouse stocks were carried out at the Biological and Medical Research Division, Argonne National Laboratory. The results of these studies, plus the mating, litter, and pre-experimental stock records, were routinely coded on IBM cards for statistical analysis and record maintenance. Also retained were the survival data from studies performed in the period 1943-1953 at the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. The card-image data files have been corrected where necessary and refiled on hard disks for long-term storage and ease of accessibility. In this report, the individual studies and data files are described, and pertinent factors regarding caging, husbandry, radiation procedures, choice of animals, and other logistical details are summarized. Some of the findings are also presented. Descriptions of the different mouse stocks and hybrids are included in an appendix; more than three dozen stocks were involved in these studies. Two other appendices detail the data files in their original card-image format and the numerical codes used to describe the animal`s exit from an experiment and, for some studies, any associated pathologic findings. Tabular summaries of sample sizes, dose levels, and other variables are also given to assist investigators in their selection of data for analysis. The archive is open to any investigator with legitimate interests and a willingness to collaborate and acknowledge the source of the data and to recognize appropriate conditions or caveats.

  2. A prospective study to evaluate a new residential community reintegration programme for severe chronic brain injury: the Brain Integration Programme.

    NARCIS (Netherlands)

    Geurtsen, G.J.; Martina, J.D.; Heugten, C.M. van; Geurts, A.C.H.

    2008-01-01

    PURPOSE: To assess the effectiveness of a residential community reintegration programme for participants with chronic sequelae of severe acquired brain injury that hamper community functioning. DESIGN: Prospective cohort study. SUBJECTS: Twenty-four participants with acquired brain injury (traumatic

  3. Management of postoperative radiation injury of the urinary bladder by hyperbaric oxygen (HBO)

    Energy Technology Data Exchange (ETDEWEB)

    Peusch-Dreyer, D.; Dreyer, K.H. [Zentrum fuer Tauch- und Ueberdruckmedizin (ZETUeM), Bremen (Germany); Mueller, C.D. [Druckkammerzentrum Magdeburg (Germany); Carl, U. [Klinik fuer Strahlentherapie und Radioonkologie, Universitaet Duesseldorf (Germany)

    1998-11-01

    Aim: In many case reports the success of treatment of late complications of radiotherapy with hyperbaric oxygenation (HBO) has been shown. This synopsis attempts to review HBO in the treatment of chronic radiation injury of the bladder. Patients and methods: Three female patients who had developed urge-incontinence after a Wertheim operation and combined brachy-teletherapy with cobalt-60 and afterloading and did not respond to various drug therapies, were treated with HBO to a maximum of 40 applications. Results: In all patients HBO haltered and inverted the dynamic process underlying chronic bladder changes after irradiation. Rationales for the HBO are the reduction of tissue hypoxia and the induction of neoangiogenesis. Conclusions: There are no prospective trials up to date showing the benefit of HBO to urinary disorders caused by radiation cystitis. The positive results of our retrospective study should encourage clinicians to initiate prospective studies with the use of HBO in the treatment of radiation cystitis. (orig.) [Deutsch] Ziel: Ueber die erfolgreiche Anwendung der hyperbaren Sauerstofftherapie (HBO) zur Behandlung von Strahlenspaetkomplikationen ist in zahlreichen Publikationen berichtet worden. Ziel dieser Arbeit ist es, den Einsatz der HBO bei der Behandlung von Miktionsbeschwerden bei chronisch radiogenen Harnblasenschaeden zu bewerten. Patienten und Methode: Drei Patientinnen, die nach einer kombinierten Brachyteletherapie mit Kobalt 60 und Afterloading nach Wertheim-Operation unter einer medikamentoes nicht zu beeinflussenden Urge-Inkontinenz litten, wurden der HBO mit maximal 40 Behandlungen zugefuehrt. Ergebnisse: Die HBO war bei allen Patientinnen in der Lage, den dynamischen Krankheitsprozess der Strahlenzystitis aufzuhalten und teilweise umzukehren. Grundlage hierfuer ist die Beseitigung der Gewebshypoxie. Dieses wiederum stellt die Voraussetzung fuer eine Neovaskularisation im bestrahlten Gewebe dar. Schlussfolgerung: Prospektive Studien

  4. Chronic Prosopis glandulosa treatment blunts neutrophil infiltration and enhances muscle repair after contusion injury.

    Science.gov (United States)

    George, Cindy; Smith, Carine; Isaacs, Ashwin W; Huisamen, Barbara

    2015-01-23

    The current treatment options for soft tissue injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscle. The current study aimed to evaluate the effects of oral Prosopis glandulosa treatment on inflammation and regeneration in skeletal muscle after contusion injury, in comparison to a conventional treatment. The gastrocnemius muscle of rats was subjected to mass-drop injury and muscle samples collected after 1-, 3 h, 1- and 7 days post-injury. Rats were treated with P. glandulosa (100 mg/kg/day) either for 8 weeks prior to injury (up until day 7 post-injury), only post-injury, or with topically applied diclofenac post-injury (0.57 mg/kg). Neutrophil (His48-positive) and macrophage (F4/80-positive) infiltration was assessed by means of immunohistochemistry. Indicators of muscle satellite cell proliferation (ADAM12) and regeneration (desmin) were used to evaluate muscle repair. Chronic P. glandulosa and diclofenac treatment (p<0.0001) was associated with suppression of the neutrophil response to contusion injury, however only chronic P. glandulosa treatment facilitated more effective muscle recovery (increased ADAM12 (p<0.05) and desmin (p<0.001) expression), while diclofenac treatment had inhibitory effects on repair, despite effective inhibition of neutrophil response. Data indicates that P. glandulosa treatment results in more effective muscle repair after contusion.

  5. Baclofen reversed thermal place preference in rats with chronic constriction injury.

    Science.gov (United States)

    Salte, K; Lea, G; Franek, M; Vaculin, S

    2016-06-20

    Chronic constriction injury to the sciatic nerve was used as an animal model of neuropathic pain. Instead of frequently used reflex-based tests we used an operant thermal place preference test to evaluate signs of neuropathic pain and the effect of baclofen administration in rats with neuropathy. Chronic constriction injury was induced by four loose ligations of the sciatic nerve. Thermal place preference (45 °C vs. 22 °C and 45 °C vs. 11 °C) was measured after the ligation and after the administration of baclofen in sham and experimental rats. Rats with the chronic constriction injury spent significantly less time on the colder plate compared to sham operated animals at the combination 45 °C vs. 11 °C. After administration of baclofen (10 mg/kg s.c.), the aversion to the colder plate in rats with chronic constriction injury disappeared. At the combination 45 °C vs. 22 °C, no difference in time spent on colder and/or warmer plate was found between sham and experimental animals. These findings show the importance of cold allodynia evaluation in rats with chronic constriction injury and the effectiveness of baclofen in this neuropathic pain model.

  6. Chronic Neck Pain and Whiplash: A Case-Control Study of the Relationship between Acute Whiplash Injuries and Chronic Neck Pain

    Directory of Open Access Journals (Sweden)

    Michael D Freeman

    2006-01-01

    Full Text Available The authors undertook a case-control study of chronic neck pain and whiplash injuries in nine states in the United States to determine whether whiplash injuries contributed significantly to the population of individuals with chronic neck and other spine pain.

  7. Chronic multiple knee ligament injuries: epidemiological analysis of more than one hundred cases

    Directory of Open Access Journals (Sweden)

    Rosalvo Zosimo Bispo Júnior

    2008-01-01

    Full Text Available INTRODUCTION: Diagnosis and treatment of multiple ligament injuries of the knee remain a real challenge for most surgeons. OBJECTIVE: To find out the epidemiological profile of patients surgically treated at a Reference Service with more than one chronic ligament injury in the knee joint. MATERIALS AND METHODS: Of a total of 978 operated patients, 109 presented at least two associated ligament injuries in the same knee. Demographic and clinical variables were evaluated. RESULTS: The anterior cruciate ligament group presented a larger number of cases of ligament injuries related with sports practice and falls, while the posterior cruciate ligament and anterior cruciate ligament + posterior cruciate ligament groups presented more cases related to traffic accidents and trauma with object (weight on the knee (p<0.001. The varus group presented significantly higher values of time since injury (p<0.01. In the group with new anterior cruciate ligament injury (neoligament associated with other ligament injuries the disruption times were higher, showing statistical significance (p<0.001. CONCLUSIONS: Anterior cruciate ligament injury associated with other ligament injuries other than posterior cruciate ligament injury are related to sports practice and falls. Posterior cruciate ligament injury associated to other ligament injuries, including or not anterior cruciate ligament injury, are related to traffic accidents and direct trauma caused by an object on the knee. Significant delay between primary ligament injuries and their reconstructions generates varus deformity of the affected knee. In spite of the large delay in seeking medical treatment, few patients with neoligament anterior cruciate ligament injury and other combined disruptions will develop varus deformity.

  8. Experimental studies on radiation injury of the salivary gland

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Kazuko

    1987-06-01

    Parotid glands of male Wistar rats were irradiated. In the first group, the animals were irradiated by 4 fractions of 4 different daily doses ; 4.7 Gy, 5.7 Gy, 6.6 Gy and 7.4 Gy. Each dose corresponds to 30 Gy, 40 Gy, 50 Gy and 60 Gy by ordinary 2 Gy-a-day irradiation respectively in the estimation of TDF value. Degree of radiation injury and recovery of the parotid glands was examined histologically, and the area ratio (acini/total gland) was calculated at 1, 3 and 6 months after the completion of irradiation. In the second group, the animals were irradiated by the following schedule ; 10 fractions of 3.6 Gy daily (I-group) and 20 fractions of 1.8 Gy (II a-group), 2.2 Gy (II b-group) and 2.9 Gy (II c-group) twice-a-day, for 2 weeks, 5 days per week. Histological changes of parotid glands the irradiation, such as collapse of acini, degeneration of acinar cells, dilatation of ducts, fibrosis and fatty replacement were found. These changes increased corresponding to the absorbed dose. In 60 Gy-group the area ratio (acini/total gland) decreased with time, 1, 3 and 6 months after the irradiation (40 %, 20 % and 10 % of the control group, respectively), while, there was no remarkable change in 50 Gy-group (60 %) and 40 Gy-group (70 - 80 %). Whereas the area ratio in 30 Gy-group decreased at 1 and 3 months (80 - 85 %), it increased up to the nearly equal level of the control group at 6 months after the irradiation. It was suggested that the borderline dose which allowed the salivary gland to recover from radiation injury existed between 30 Gy and 40 Gy. The area ratio of II b-group at 1 and 3 months after the irradiation (50 %, 48 %) was nearly equal to that of I-group (53 %, 57 %). While the area ratio of II a-group (71 %, 73 %) was larger than that of I-group with a statistical significance. (J.P.N.).

  9. Chronic issues related to traumatic brain injury : traumatic brain injury is not an incident

    NARCIS (Netherlands)

    Grauwmeijer, Erik; van der Naalt, Joukje; ribbers, gerard

    2016-01-01

    Despite an increased awareness of the long-term consequences of traumatic brain injury, health care professionals often consider traumatic brain injury as an incident. However, patients with traumatic brain injury may experience long-term neurological, cognitive and behavioural problems. Due to the

  10. Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

    Science.gov (United States)

    Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

    2015-06-04

    Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model.

  11. Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Zuncheng Zheng; Guifeng Liu; Yuexia Chen; Shugang Wei

    2013-01-01

    Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.

  12. Olfactory ensheathing cell transplantation for a patient with chronic sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Zhang F

    2016-12-01

    Full Text Available Feng Zhang,1,2 Xiangzhi Meng,2 Fang Lu,2 Aixian Liu,2 Hongyun Huang1,2 1Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, 2Neurorehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, People’s Republic of China Objective: To observe the result of olfactory ensheathing cell (OEC transplantation in a patient with chronic sciatic nerve injury. Case report: A 53-year-old male patient with chronic (1 year sciatic nerve injury on left side received OEC transplantation at the lesion site. He received follow-up assessment according to the American Spinal Injury Association standard at 10 days, 6 months, and 1 year after OEC therapy. The muscle strength of his left lower limb increased and numbness decreased during the early stage of cell therapy. His motor function improved with each evaluation. His limp walking gait recovered, and numbness sensation got nearly normal after 1 year of follow-up. There were no side effects. Conclusion: OEC transplantation may be an option for chronic peripheral (sciatic nerve injury. Keywords: olfactory ensheathing cell transplantation, sciatic nerve injury, peripheral nerve injury, function improvement, neurorestoration

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

    Science.gov (United States)

    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.

  14. Chronic Spinal Injury Repair by Olfactory Bulb Ensheathing Glia and Feasibility for Autologous Therapy

    Science.gov (United States)

    Muñoz-Quiles, Cintia; Santos-Benito, Fernando F.; Llamusí, M. Beatriz; Ramón-Cueto, Almudena

    2009-01-01

    Olfactory bulb ensheathing glia (OB-OEG) promote repair of spinal cord injury (SCI) in rats after transplantation at acute or subacute (up to 45 days) stages. The most relevant clinical scenario in humans, however, is chronic SCI, in which no more major cellular or molecular changes occur at the injury site; this occurs after the third month in rodents. Whether adult OB-OEG grafts promote repair of severe chronic SCI has not been previously addressed. Rats with complete SCI that were transplanted with OB-OEG 4 months after injury exhibited progressive improvement in motor function and axonal regeneration from different brainstem nuclei across and beyond the SCI site. A positive correlation between motor outcome and axonal regeneration suggested a role for brainstem neurons in the recovery. Functional and histological outcomes did not differ at subacute or chronic stages. Thus, autologous transplantation is a feasible approach as there is time for patient stabilization and OEG preparation in human chronic SCI; the healing effects of OB-OEG on established injuries may offer new therapeutic opportunities for chronic SCI patients. PMID:19915486

  15. Chronic radiation proctopathy:A practical review of endoscopic treatment

    Institute of Scientific and Technical Information of China (English)

    Luciano Lenz; Rachel Rohr; Frank Nakao; Ermelindo Libera; Angelo Ferrari

    2016-01-01

    Chronic radiation proctopathy(CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbidmortality. Endoscopy has a role in the diagnosis,staging and treatment of this disease. Currently available endoscopic modalities are formalin,potassium titanyl phosphate laser,neodymium:yttrium-aluminum-garnet laser,argon laser,bipolar electrocoagulation(BiCAP),heater probe,band ligation,cryotherapy,radiofrequency ablation and argon plasma coagulation(APC). Among these options,APC is the most promising.

  16. Effects in Plant Populations Resulting from Chronic Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, Stanislav A.; Volkova, Polina Yu.; Vasiliyev, Denis V.; Dikareva, Nina S.; Oudalova, Alla A. [Russian Institute of Agricultural Radiology and Agroecology, 249032, Obninsk (Russian Federation)

    2014-07-01

    environment activates genetic mechanisms, changing a population's resistance to exposure. However, there are ecological situations in which enhanced resistance has not evolved or has not persisted. Consequently, there are good theoretical and practical reasons for more attention being paid to the mechanisms by which populations becomes more radioresistant and to those situations where radio-adaptation appears not to be taking place. Since radio-adaptation plays an important role in response of populations on radiation exposure, this process needs to be incorporated into management programmes. To this very day, the effects of chronic exposure on living organisms and populations remain poorly explored, and represent a much needed field of research. In spite of the long history of the research, we are still far from complete understanding underlying processes in exposed populations. Neglecting field-collected data in favour of simplified short-term experiments that tend to overestimate adverse effects will obviously have detrimental effect for understanding, predicting, and mitigating consequences of the radiation impact on the environment. Much more is to be elucidated in our understanding before we will be able to give an objective and comprehensive assessment of the biological consequences of chronic, low-level radiation exposures to natural plant and animal populations. (authors)

  17. Investigation of Chronic Pain Following Traumatic Brain Injury

    Science.gov (United States)

    2014-03-01

    to those in other chronic pain states such as migraine and fibromyalgia when controlled for co-morbid insomnia, depression and PTSD. The study groups...to be compared for this work include patients with chronic migraine, fibromyalgia , post-traumatic pain post mTBI, asymptomatic individuals post mTBI...migraine, fibromyalgia , post-traumatic pain post mTBI, asymptomatic individuals post mTBI, and normal controls. The understanding of the

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

    Science.gov (United States)

    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.

  19. Magnetic resonance imaging of spinal cord injury in chronic stage

    Energy Technology Data Exchange (ETDEWEB)

    Tobimatsu, Haruki; Nihei, Ryuichi; Kimura, Tetsuhiko; Yano, Hideo; Touyama, Tetsuo; Tobimatsu, Yoshiko; Suyama, Naoto; Yoshino, Yasumasa (National Rehabilitation Center for the Disabled, Tokorozawa, Saitama (Japan))

    1991-10-01

    Magnetic resonance (MR) images of a total of 195 patients with cervical (125) or thoracic (70) spinal cord injury were reviewed. The imaging studies of the spinal cord lesions were correlated with clinical manifestations. Sequential MR imaging revealed hypointensity on T1-weighted images (T1WI) and hyperintensity on T2-weighted images (T2WI) in all patients, except for five patients showing no signal changes and two showing isointensity, suggesting gliosis, myelomalacia, and syringomyelia. Spinal cord lesions were classified into four types: small lesions, large lesions, complete transverse, and longitudinal rupture. These lesions were well correlated with the severity of injury and paralysis. Complete paralysis was frequently associated with enlarged, complete transverse for cervical spinal cord injury, and longitudinal ruptured or thinned complete transverse for thoracic spinal cord injury. The height of paralysis was well in agreement with that of lesions. For incomplete paralysis, localized lesions were seen within the spinal cord, coinciding with the paralysis or severity. Traumatic syringomyelia was seen in 17 patients (8.7%)-- for the cervical site (10 patients, 8%) and the thoracic site (7 patients, 10%). When homogeneous and marginally clear hypointensity is shown on T1-weighted images and vacuolated hyperintensity is shown on T2-weighted images, in addition to lesions spreading two or more cords or 1.5 or more cords above the nervous root level of paralysis, traumatic syringomyelia is strongly suspected, requiring the follow up observation. (N.K.).

  20. Combination of Radiation and Burn Injury Alters FDG Uptake in Mice

    OpenAIRE

    2012-01-01

    Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure, on glucose metabolism in mice using [18F] Fluorodeoxyglucose (18FDG). Groups of male mice weighing approximately 30g were studied. Group 1 was irradiated with a 137Cs source (9 Gy). Group 2 received full thickness burn injury on 25% total body surface area followed by resuscitated with saline (2mL, IP)...

  1. TGF-beta, radiation-induced pulmonary Injury and lung cancer

    NARCIS (Netherlands)

    Vujaskovic, Z; Groen, HJM

    2000-01-01

    Purpose: To determine whether changes in TGF-beta plasma levels during radiation therapy may be useful in predicting radiation-induced pulmonary injury and tumour response in non-small-cell lung cancer (NSCLC) patients. Materials and methods: Plasma TGF-beta was investigated in 27 patients with stag

  2. The Relation of Mild Traumatic Brain Injury to Chronic Lapses of Attention

    Science.gov (United States)

    Pontifex, Matthew B.; Broglio, Steven P.; Drollette, Eric S.; Scudder, Mark R.; Johnson, Chris R.; O'Connor, Phillip M.; Hillman, Charles H.

    2012-01-01

    We assessed the extent to which failures in sustained attention were associated with chronic mild traumatic brain injury (mTBI) deficits in cognitive control among college-age young adults with and without a history of sport-related concussion. Participants completed the ImPACT computer-based assessment and a modified flanker task. Results…

  3. Treatment of Oppositional Behavior in Children of Parents with Brain Injury and Chronic Pain.

    Science.gov (United States)

    Ducharme, Joseph M.; Davidson, Amy; Rushford, Nancy

    2002-01-01

    This case study evaluated effects of errorless compliance training on cooperation of sons of two fathers with brain injury and chronic pain. Following treatment, children displayed high levels of compliance to parent requests as well as generalization and maintenance of treatment gains. Errorless compliance training is recommended to foster…

  4. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    GURPREET KAUR

    2015-03-01

    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  5. The effects of chronic fluoxetine treatment following injury of medial frontal cortex in mice.

    Science.gov (United States)

    McAllister, Brendan B; Spanswick, Simon C; Patel, Payal P; Barneto, Alison A; Dyck, Richard H

    2015-09-01

    Injury of the brain is a leading cause of long-term disability. Recent evidence indicates that the selective serotonin reuptake inhibitor drug fluoxetine may be beneficial when administered following brain injury. However, its potential to promote recovery and the mechanisms by which it might do so require further characterization. In the present experiment, fluoxetine was administered to mice for 4 weeks following injury of medial frontal cortex (MFC). MFC injury altered behavior, reducing locomotion, decreasing swim speed in the Morris water task, and decreasing anxiety-like behavior in the elevated plus maze. Fluoxetine treatment did not affect these behavioral alterations, but it did increase the social dominance of the injured mice, as assessed by the tube test. Fluoxetine treatment also hastened learning of a T-maze position discrimination task, independently of lesion condition. Anatomically, fluoxetine failed to decrease lesion size, increase the survival of cells born 1-week post injury in the hippocampal dentate gyrus, or reverse the reduction in spine density in layer II/III pyramidal neurons in cingulate cortex caused by the lesions. Fluoxetine did, however, increase the dendritic arborization of these cells, which was reduced in the mice with lesions. Thus, while not all the effects of MFC injury were ameliorated, the behavioral outcome of mice with MFC injuries was improved, and one of the neuroanatomical sequelae of the lesions counteracted, by chronic fluoxetine, further contributing to the evidence that fluoxetine could be a useful treatment following brain injury.

  6. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    Science.gov (United States)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  7. Liver Injury Induced by Anticancer Chemotherapy and Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Y. Maor

    2013-01-01

    Full Text Available Cytotoxic chemotherapy prolongs survival of patients with advanced and metastatic tumors. This is, however, a double-edged sword with many adverse effects. Since the liver has a rich blood supply and plays an active role in the metabolism of medications, it is not surprising that there can be hepatic injury related to chemotherapy. In addition, radioembolization may affect the parenchyma of normal and cirrhotic livers. We review chemotherapy-associated liver injury in patients with colorectal liver metastases, including downsizing chemotherapy and neoadjuvant chemotherapy. We discuss the mechanism of the hepatic injury, secondary to reactive oxygen species, and the spectrum of hepatic injury including, steatosis, steatohepatitis, hepatic sinusoidal injury and highlight the pharmacogenomics of such liver insults. Methods for reducing and treating the hepatotoxicity are discussed for specific agents including tamxifen and the newly introduced targeted antibodies.

  8. 皮下埋线治疗慢性软组织损伤53例%53 cases of chronic soft tissue injury using subcutaneous line embedding therapy

    Institute of Scientific and Technical Information of China (English)

    叶立汉; 胡亚明

    2003-01-01

    @@ INTRODUCTION Acupuncture and ventouse can dredge meridian, activate blood circulation and relieve pain thus is effective to chronic soft tissue injury.We investigated a kind of method using subcutaneous line-embedding therapy to cure chronic soft tissue injury and explore a high performance and effective method in curing chronic soft tissue injury.

  9. Chronic neck pain disability due to an acute whiplash injury

    NARCIS (Netherlands)

    Nederhand, Marc J.; Hermens, Hermie J.; IJzerman, Maarten J.; Turk, Dennis C.; Zilvold, Gerrit

    2003-01-01

    Several theories about musculoskeletal pain syndromes such as whiplash-associated disorder (WAD) suggest that pain and muscle activity interact and may contribute to the chronicity of symptoms. Studies using surface electromyography (sEMG) have demonstrated abnormal muscle activation patterns of the

  10. Serum Markers and Intestinal Mucosal Injury in Chronic Gastrointestinal Ischemia

    NARCIS (Netherlands)

    D. van Noord (Désirée); P.B.F. Mensink (Peter); R.J. de Knegt (Robert); M. Ouwendijk (Martine); J. Francke (Jan Paul); A.J. van Vuuren (Hanneke); B.E. Hansen (Bettina); E.J. Kuipers (Ernst)

    2010-01-01

    textabstractBackground: Diagnosing chronic gastrointestinal ischemia (CGI) is a challenging problem in clinical practice. Serum markers for CGI would be of great diagnostic value as a non-invasive test method. Aims: This study investigated serum markers in patients with well-defined ischemia. Furthe

  11. Combination of Radiation and Burn Injury Alters FDG Uptake in Mice

    Science.gov (United States)

    Carter, Edward A.; Winter, David; Tolman, Crystal; Paul, Kasie; Hamrahi, Victoria; Tompkins, Ronald; Fischman, Alan J.

    2012-01-01

    Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure, on glucose metabolism in mice using [18F] Fluorodeoxyglucose (18FDG). Groups of male mice weighing approximately 30g were studied. Group 1 was irradiated with a 137Cs source (9 Gy). Group 2 received full thickness burn injury on 25% total body surface area followed by resuscitated with saline (2mL, IP). Group 3 received radiation followed 10 minutes later by burn injury. Group 4 were sham treated controls. After treatment, the mice were fasted for 23 hours and then injected (IV) with 50 µCi of 18FDG. One hour post injection, the mice were sacrificed and biodistribution was measured. Positive blood cultures were observed in all groups of animals compared to the shams. Increased mortality was observed after 6 days in the burn plus radiated group as compared to the other groups. Radiation and burn treatments separately or in combination produced major changes in 18FDG uptake by many tissues. In the heart, brown adipose tissue (BAT) and spleen, radiation plus burn produced a much greater increase (p<0.0001) in 18FDG accumulation than either treatment separately. All three treatments produced moderate decreases in 18FDG accumulation (p<0.01) in the brain and gonads. Burn injury, but not irradiation, increased 18FDG accumulation in skeletal muscle; however the combination of burn plus radiation decreased 18FDG accumulation in skeletal muscle. This model may be useful for understanding the effects of burns + irradiation injury on glucose metabolism and in developing treatments for victims of injuries produced by the combination of burn plus irradiation. PMID:23143615

  12. Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

    Science.gov (United States)

    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 responses in

  13. Late health effects of chronic radiation exposure of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Yarmoshenko, Ilia V.; Malinovsky, Georgy P.; Konshina, Lidia G.; Zhukovsky, Michael V. [Institute of Industrial Ecology UB RAS, 620219, 20, Sophy Kovalevskoy St., Ekaterinburg (Russian Federation); Tuzankina, Irina A. [Institute of Immunology and Physiology UB RAS, 620049, 106, Pervomayskaya St., Ekaterinburg (Russian Federation)

    2014-07-01

    infectious etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

  14. Mitochondrial Roles and Cytoprotection in Chronic Liver Injury

    Directory of Open Access Journals (Sweden)

    Davide Degli Esposti

    2012-01-01

    Full Text Available The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts.

  15. Combined anterior cruciate ligament and posterolateral reconstruction of the knee using allograft tissue in chronic knee injuries.

    Science.gov (United States)

    Fanelli, Gregory C; Fanelli, David G; Edson, Craig J; Fanelli, Matthew G

    2014-10-01

    Combined anterior cruciate ligament (ACL) and posterolateral injury of the knee can result in significant functional instability for the affected individual. Both components of the instability must be treated to maximize the probability of success for the surgical procedure. Higher failure rates of the ACL reconstruction have been reported when the posterolateral instability has been left untreated. The purpose of this article is to describe our surgical technique, and present the results of 34 chronic combined ACL posterolateral reconstructions in 34 knees using allograft tissue, and evaluating these patient outcomes with KT 1000 knee ligament arthrometer, Lysholm, Tegner, and Hospital for Special Surgery knee ligament rating scales. In addition, observations regarding patient demographics with combined ACL posterolateral instability, postoperative range of motion loss, postinjury degenerative joint disease, infection rate, return to function, and the use of radiated and nonirradiated allograft tissues will be presented.

  16. Analysis of reproductive function in persons exposed to chronic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kossenko, M.M.; Ostroumova, E.V.; Vyushkova, O.V. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)

    2000-05-01

    The purpose of the study was to analyze the reproductive function in individuals exposed to radiation in the riverside villages on the Techa in the Southern Urals. The exposure of the population, numbering 28000, occurred in 1950-1956 as a result of discharges into the river of radioactive wastes from the Mayak facility for processing weapon plutonium. The residents were exposed to chronic radiation, both external and internal. The range of exposure doses to gonads was sufficiently wide: 20-1270 mSv. However, the distribution of doses among the exposed individuals was ununiform, and the proportion of people whose dose was below 120 mGy accounted for 74%. The following characteristics of exposed women were analyzed: menstrual function, outcomes of pregnancy, birth rates, health status for newborns. The analysis of the menstrual function in exposed women showed that in persons exposed in childhood, menarche was registered at the age of 14.3 years, on the average (based on literature sources, menarche is attained at the age of 13 for unexposed population). The mean age at menopause was 47.9 years for exposed women (the respective mean value for Russia is 50.8 years). Pregnancy outcomes were analyzed in 9000 exposed women. The rate of medical and criminal abortions was estimated as 79 per 100 labors. The rate of spontaneous abortions for exposed women was slightly higher, 3.11%, than for controls, 2.30%; these difference, however, were statistically insignificant. The total loss of fetus or neonate (unfavorable outcomes of pregnancy: spontaneous abortions, stillbirths, early neonatal death) was estimated to be 4.58% at zero dose. Exposure to gonads at the dose 1 Sv, estimated using the above-indicated method, yielded 3% of additional unfavorable outcomes of pregnancy. It was shown, based on the analysis of birth rates for the Techa Cohort that they had not undergone any essential changes over the first 25 years of exposure compared to the respective coefficients for

  17. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

    Science.gov (United States)

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-10-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas.

  18. Chronic neck pain disability due to an acute whiplash injury.

    Science.gov (United States)

    Nederhand, Marc J; Hermens, Hermie J; IJzerman, Maarten J; Turk, Dennis C; Zilvold, Gerrit

    2003-03-01

    Several theories about musculoskeletal pain syndromes such as whiplash-associated disorder (WAD) suggest that pain and muscle activity interact and may contribute to the chronicity of symptoms. Studies using surface electromyography (sEMG) have demonstrated abnormal muscle activation patterns of the upper trapezius muscles in the chronic stage of WAD (grade II). There are, however, no studies that confirm that these muscle reactions are initiated in the acute stage of WAD, nor that these muscle reactions persist in the transition from acute neck pain to chronic neck pain disability. We analyzed the muscle activation patterns of the upper trapezius muscles in a cohort of 92 subjects with acute neck pain due to a motor vehicle accident (MVA). This cohort was followed up in order to evaluate differences in muscular activation patterns between subjects who have recovered and those subjects who have not recovered following an acute WAD and developed chronic neck pain. sEMG parameters were obtained at 1, 4, 8, 12, and 24 weeks after an MVA. The level of muscle reactivity (the difference in pre- and post-exercise EMG levels) and the level of muscle activity during an isometric and a dynamic task were used as EMG parameters. The results revealed no elevated muscle reactivity either in the acute stage, or during the follow-up period. The results of both the isometric and dynamic task, showed statistically significant different EMG levels between four neck pain disability subgroups (analysis of variance reaching P-levels of 0.000), with an inverse relationship between the level of neck pain disability and EMG level. Furthermore, follow-up assessments of the EMG level during these two tasks, did not show a time related change. In conclusion, in subjects with future disability, the acute stage is characterized by a reorganization of the muscular activation of neck and shoulder muscles, possibly aimed at minimizing the use of painful muscles. This change of motor control, is in

  19. RADIATION DOSE–VOLUME EFFECTS IN RADIATION-INDUCED RECTAL INJURY

    Science.gov (United States)

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

    2010-01-01

    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 TD50 = 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. PMID:20171506

  20. Characterization of chronic pain and somatosensory function in spinal cord injury subjects.

    Science.gov (United States)

    Defrin, R; Ohry, A; Blumen, N; Urca, G

    2001-01-01

    The pathophysiology of the chronic pain following spinal cord injury (SCI) is unclear. In order to study it's underlying mechanism we characterized the neurological profile of SCI subjects with (SCIP) and without (SCINP) chronic pain. Characterization comprised of thermal threshold testing for warmth, cold and heat pain and tactile sensibility testing of touch, graphesthesia and identification of speed of movement of touch stimuli on the skin. In addition, spontaneously painful areas were mapped in SCIP and evoked pathological pain--allodynia, hyperpathia and wind-up pain evaluated for both groups. Both SCIP and SCINP showed similar reductions in both thermal and tactile sensations. In both groups thermal sensations were significantly more impaired than tactile sensations. Chronic pain was present only in skin areas below the lesion with impaired or absent temperature and heat-pain sensibilities. Conversely, all the thermally impaired skin areas in SCIP were painful while painfree areas in the same subjects were normal. In contrast, chronic pain could be found in skin areas without any impairment in tactile sensibilities. Allodynia could only be elicited in SCIP and a significantly higher incidence of pathologically evoked pain (i.e. hyperpathia and wind-up pain) was seen in the chronic pain areas compared to SCINP. We conclude that damage to the spinothalamic tract (STT) is a necessary condition for the occurrence of chronic pain following SCI. However, STT lesion is not a sufficient condition since it could also be found in SCINP. The abnormal evoked pain seen in SCIP is probably due to neuronal hyperexcitability in these subjects. The fact that apparently identical sensory impairments manifest as chronic pain and hyperexcitability in one subject but not in another implies that either genetic predisposition or subtle differences in the nature of spinal injury determine the emergence of chronic pain following SCI.

  1. Does hypokalemia contribute to acute kidney injury in chronic laxative abuse?

    Directory of Open Access Journals (Sweden)

    Eun-Young Lee

    2015-06-01

    Full Text Available Prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease, known as “hypokalemic nephropathy,” but it is not clear whether it contributes to acute kidney injury (AKI. A 42-year-old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa (AN-P, developed an anuric AKI requiring hemodialysis and a mild AKI 2 months later. Both episodes of AKI involved severe to moderate hypokalemia (1.2 and 2.7 mmol/L, respectively, volume depletion, and mild rhabdomyolysis. The histologic findings of the first AKI revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury. Along with these observations, the intertwined relationship among precipitants of recurrent AKI in AN-P is discussed, and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia-induced AKI.

  2. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury.

    Science.gov (United States)

    Williamson, John; Isaki, Emi

    2015-01-01

    The use of a modified Facial Affect Recognition (FAR) training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years) traumatic brain injury (TBI). The modified FAR training was administered via telepractice to target social communication skills. Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-play. Pre- and post-therapy measures included static facial photos to identify emotion and the Prutting and Kirchner Pragmatic Protocol for social communication. Both participants with chronic TBI showed gains on identifying facial emotions on the static photos.

  3. Late results of mucosal proctectomy and colo-anal sleeve anastomosis for chronic irradiation rectal injury

    Energy Technology Data Exchange (ETDEWEB)

    Browning, G.G.P.; Varma, J.S.; Smith, A.N.; Small, W.P.; Duncan, W.

    1987-01-01

    Ten patients with severe chronic irradiation injury to the rectum were treated by mucosal proctectomy and colo-anal sleeve anastomosis. The indications were: recurrent rectal bleeding (five), stricture (three), fistula (one) and intractable pain (one). Overall follow-up has ranged from 8 to 77 months (mean 40 months). In the present survivors (n=7) the follow-up ranges from 18 to 77 months (mean 52 months). Six patients have been followed up for more than 3 years and four for more than 5 years. There was no operative mortality. Three anastomotic strictures occurred but the protecting stoma could be closed in all but one patient. Continence was acceptable although urgency and frequency of defaecation were troublesome symptoms. The operation is recommended for life-threatening, haemorrhagic chronic irradiation injury to the rectum.

  4. Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries.OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats.DESIGN: A randomized controlled animal trial.SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University.MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220 - 250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point.METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7 - 10 days.MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively.RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly

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

    Energy Technology Data Exchange (ETDEWEB)

    Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

    2013-09-27

    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.

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

    Directory of Open Access Journals (Sweden)

    B.H. Bakkal

    2013-09-01

    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); 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.

  8. Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury.

    Science.gov (United States)

    Schaub, Johanna R; Malato, Yann; Gormond, Coralie; Willenbring, Holger

    2014-08-21

    Hepatocytes provide most liver functions, but they can also proliferate and regenerate the liver after injury. However, under some liver injury conditions, particularly chronic liver injury where hepatocyte proliferation is impaired, liver stem cells (LSCs) are thought to replenish lost hepatocytes. Conflicting results have been reported about the identity of LSCs and their contribution to liver regeneration. To address this uncertainty, we followed candidate LSC populations by genetic fate tracing in adult mice with chronic liver injury due to a choline-deficient, ethionine-supplemented diet. In contrast to previous studies, we failed to detect hepatocytes derived from biliary epithelial cells or mesenchymal liver cells beyond a negligible frequency. In fact, we failed to detect hepatocytes that were not derived from pre-existing hepatocytes. In conclusion, our findings argue against LSCs, or other nonhepatocyte cell types, providing a backup system for hepatocyte regeneration in this common mouse model of chronic liver injury.

  9. Evidence against a Stem Cell Origin of New Hepatocytes in a Common Mouse Model of Chronic Liver Injury

    Directory of Open Access Journals (Sweden)

    Johanna R. Schaub

    2014-08-01

    Full Text Available Hepatocytes provide most liver functions, but they can also proliferate and regenerate the liver after injury. However, under some liver injury conditions, particularly chronic liver injury where hepatocyte proliferation is impaired, liver stem cells (LSCs are thought to replenish lost hepatocytes. Conflicting results have been reported about the identity of LSCs and their contribution to liver regeneration. To address this uncertainty, we followed candidate LSC populations by genetic fate tracing in adult mice with chronic liver injury due to a choline-deficient, ethionine-supplemented diet. In contrast to previous studies, we failed to detect hepatocytes derived from biliary epithelial cells or mesenchymal liver cells beyond a negligible frequency. In fact, we failed to detect hepatocytes that were not derived from pre-existing hepatocytes. In conclusion, our findings argue against LSCs, or other nonhepatocyte cell types, providing a backup system for hepatocyte regeneration in this common mouse model of chronic liver injury.

  10. Three-year follow-up results of a residential community reintegration program for patients with chronic acquired brain injury.

    NARCIS (Netherlands)

    Geurtsen, G.J.; Heugten, C.M. van; Martina, J.D.; Rietveld, A.C.; Meijer, R.; Geurts, A.C.H.

    2012-01-01

    OBJECTIVE: To evaluate outcomes of a residential community reintegration program 3 years after treatment on independent living, societal participation, emotional well-being, and quality of life in patients with chronic acquired brain injury and psychosocial problems hampering societal participation.

  11. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

    OpenAIRE

    Schmid Axel; Küttner Axel; Amann Kerstin U; Opgenoorth Mirian; Schnellhardt Susanne; Jacobi Johannes; Eckardt Kai-Uwe; Hilgers Karl F

    2010-01-01

    Abstract Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of wh...

  12. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury

    OpenAIRE

    John Williamson; Emi Isaki

    2015-01-01

    The use of a modified Facial Affect Recognition (FAR) training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years) traumatic brain injury (TBI).  The modified FAR training was administered via telepractice to target social communication skills.  Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and ro...

  13. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury

    OpenAIRE

    Williamson, John; ISAKI, EMI

    2015-01-01

    The use of a modified Facial Affect Recognition (FAR) training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years) traumatic brain injury (TBI). The modified FAR training was administered via telepractice to target social communication skills. Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-pl...

  14. Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

    Science.gov (United States)

    2014-10-01

    RNSH. Kathy is a registered nurse and Francesca has many years clinical trials experience. Kathy and Francesca have continued the job sharing...Questionnaire Q4 September 2012 • Treatment Algorithm for Autonomic Dysreflexia ( Hypertensive Crisis) in Spinal Cord (10 April2006) CURRENT • Treatment...Algorithm for Autonomic Dysreflexia ( Hypertensive Crisis) in Spinal Cord Injury (2010) CURRENT Approval 20/2/2013 • Protocol Version 4 dated 12

  15. Baseline donor chronic renal injury confers the same transplant survival disadvantage for DCD and DBD kidneys.

    Science.gov (United States)

    Kosmoliaptsis, V; Salji, M; Bardsley, V; Chen, Y; Thiru, S; Griffiths, M H; Copley, H C; Saeb-Parsy, K; Bradley, J A; Torpey, N; Pettigrew, G J

    2015-03-01

    Histological assessment of baseline chronic kidney injury may discriminate kidneys that are suitable for transplantation, but has not been validated for appraisal of donation after circulatory death (DCD) kidneys. 'Time-zero' biopsies for 371 consecutive, solitary, deceased-donor kidneys transplanted at our center between 2006 and 2010 (65.5% DCD, 34.5% donation after brain death [DBD]) were reviewed and baseline chronic degenerative injury scored using Remuzzi's classification. High scores correlated with donor age and extended criteria donors (42% of donors), but the spectrum of scores was similar for DCD and DBD kidneys. Transplant outcomes for kidneys scoring from 0 to 4 were comparable (1 and 3 year graft survival 95% and 92%), but were much poorer for kidneys scoring ≥5, with 1 year graft survival only 73%, and 12.5% suffering primary nonfunction. Critically, high Remuzzi scores conferred the same survival disadvantage for DCD and DBD kidneys. On multi-variable regression analysis, time-zero biopsy score was the only independent predictor for graft survival, whereas one-year graft estimated glomerular filtration rate (eGFR) correlated with donor age and biopsy score. In conclusion, the relationship between severity of chronic kidney injury and transplant outcome is similar for DCD and DBD kidneys. Kidneys with Remuzzi scores of ≤4 can be implanted singly with acceptable results.

  16. Optic Nerve Injury in a Patient with Chronic Allergic Conjunctivitis

    Directory of Open Access Journals (Sweden)

    Ribhi Hazin

    2014-01-01

    Full Text Available Manipulation of the optic nerve can lead to irreversible vision changes. We present a patient with a past medical history of skin allergy and allergic conjunctivitis (AC who presented with insidious unexplained unilateral vision loss. Physical exam revealed significant blepharospasm, mild lid edema, bulbar conjunctival hyperemia, afferent pupillary defect, and slight papillary hypertrophy. Slit lamp examination demonstrated superior and inferior conjunctival scarring as well as superior corneal scarring but no signs of external trauma or neurological damage were noted. Conjunctival cultures and cytologic evaluation demonstrated significant eosinophilic infiltration. Subsequent ophthalmoscopic examination revealed optic nerve atrophy. Upon further questioning, the patient admitted to vigorous itching of the affected eye for many months. Given the presenting symptoms, history, and negative ophthalmological workup, it was determined that the optic nerve atrophy was likely secondary to digital pressure from vigorous itching. Although AC can be a significant source of decreased vision via corneal ulceration, no reported cases have ever described AC-induced vision loss of this degree from vigorous itching and chronic pressure leading to optic nerve damage. Despite being self-limiting in nature, allergic conjunctivitis should be properly managed as extreme cases can result in mechanical compression of the optic nerve and compromise vision.

  17. Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury.

    Science.gov (United States)

    Wang, Ying-Ying; Jiang, Hong; Pan, Jun; Huang, Xiao-Ru; Wang, Yu-Cheng; Huang, Hong-Feng; To, Ka-Fai; Nikolic-Paterson, David J; Lan, Hui-Yao; Chen, Jiang-Hua

    2017-02-16

    Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers. CD68(+)/α-SMA(+) cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and α-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of α-SMA(+) myofibroblasts in renal allografts originated from recipient bone marrow-derived macrophages. Knockout of Smad3 protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in Smad3-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow-derived M2-type macrophages to myofibroblasts in the renal allograft is regulated via a Smad3-dependent mechanism.

  18. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  19. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation. PMID:26795421

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

    Energy Technology Data Exchange (ETDEWEB)

    Ó Broin, Pilib [Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Department of Mathematical Sciences, Yeshiva University, New York, New York (United States); Vaitheesvaran, Bhavapriya [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Saha, Subhrajit [Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Hartil, Kirsten [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Chen, Emily I. [Department of Pharmacology, Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York (United States); Goldman, Devorah; Fleming, William Harv [Department of Medicine, Oregon Health and Science University, Portland, Oregon (United States); Kurland, Irwin J. [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Guha, Chandan, E-mail: cguha@montefiore.org [Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Golden, Aaron, E-mail: aaron.golden@einstein.yu.edu [Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Department of Mathematical Sciences, Yeshiva University, New York, New York (United States)

    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.

  1. Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

    OpenAIRE

    Keirstead Hans S; Nistor Gabriel; Radojicic Milan

    2007-01-01

    Abstract Background Chronic spinal cord injury (SCI) can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Methods Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an In...

  2. Future directions in therapy of whole body radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. [The future of hyperbaric oxygen therapy: added value in the treatment of late radiation injury?

    NARCIS (Netherlands)

    Geel, A.N. van; Poortmans, P.; Koppert, L.B.

    2015-01-01

    There is some evidence for the benefit of hyperbaric oxygen therapy in late radiation tissue injury (LRTI) affecting the head, neck and lower bowel, but there is little evidence for or against the benefit in other tissues (e.g. the breast) affected by LRTI. There is a need for large prospective tria

  4. Radiological and functional assessment of radiation-induced lung injury in the rat

    NARCIS (Netherlands)

    Vujaskovic, Z; Down, JD; van t'Veld, AA; Mooyaart, EL; Meertens, H; Piers, DA; Szabo, BG; Konings, AWT

    1998-01-01

    The purpose of this study is to develop an experimental model to measure localized radiation-induced lung injury using multiple end-points including breathing frequency, high-resolution computed tomography (CT), and radionuclide perfusion. The rats were anaesthetized and the right lung irradiated wi

  5. Fear of movement/(re)injury and muscular reactivity in chronic low back pain patients : an experimental investigation

    NARCIS (Netherlands)

    Vlaeyen, Johan W.S.; Seelen, HAM; Peters, Madelon L.; de Jong, Peter; Aretz, E; Beisiegel, E; Weber, WEJ

    1999-01-01

    This experiment was set up to test the hypothesis that confrontation with feared movements would lead to symptom-specific muscular reactivity in chronic low back pain patients who report high fear of movement/(re)injury. Thirty-one chronic low back pain patients were asked to watch a neutral nature

  6. Combined Injury Modeling: Radiation and Burn Workshop Report

    Science.gov (United States)

    2010-10-01

    Sepsis resulting from burns differs from that from radiation. Viruses and fungi , in addition to bacteria, can enter the bloodstream and develop...In Reviews in Cancer Biology & Therapeutics (ed. Kasid, Notario, Haimovitz-Friedman and Bar-Eli) Research Signpost, 2007. Williams C. Successful

  7. Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

    Directory of Open Access Journals (Sweden)

    Su Lin

    2011-11-01

    Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

  8. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun; Kang, Jeong Wook [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Dong Won [Department of Plastic Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Oh, Sang Ho [Department of Dermatology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Yun-Sil [College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewah Womans University, Seoul 120-750 (Korea, Republic of); Lee, Eun-Jung [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    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.

  10. Palmitoylethanolamide regulates development of intestinal radiation injury in a mast cell dependent manner

    Science.gov (United States)

    Wang, Junru; Zheng, Junying; Kulkarni, Ashwini; Wang, Wen; Garg, Sarita; Prather, Paul L.; Hauer-Jensen, Martin

    2014-01-01

    Background Mast cells and neuroimmune interactions regulate the severity of intestinal radiation mucositis, a dose-limiting toxicity during radiation therapy of abdominal malignancies. Aims Because endocannabinoids regulate intestinal inflammation, we investigated the effect of the cannabimimetic, palmitoylethanolamide (PEA), in a mast competent (+/+) and mast cell deficient (Ws/Ws) rat model. Methods Rats underwent localized, fractionated intestinal irradiation and received daily injections with vehicle or PEA from 1 day before until 2 weeks after radiation. Intestinal injury was assessed non-invasively by luminol bioluminescence, and, at 2 weeks, by histology, morphometry, and immunohistochemical analysis, gene expression analysis, and pathway analysis. Results Compared to +/+ rats, Ws/Ws rats sustained more intestinal structural injury (p=0.01), mucosal damage (p=0.02), neutrophil infiltration (p=0.0003), and collagen deposition (p=0.004). PEA reduced structural radiation injury (p=0.02), intestinal wall thickness (p=0.03), collagen deposition (p=0.03), and intestinal inflammation (p=0.02) in Ws/Ws rats, but not in +/+ rats. PEA inhibited mast cell-derived cellular immune response and anti-inflammatory IL-6 and IL-10 signaling, and activated the prothrombin pathway in +/+ rats. In contrast, while PEA suppressed non-mast cell derived immune responses, it increased anti-inflammatory IL-10 and IL-6 signaling and decreased activation of the prothrombin pathway in Ws/Ws rats. Conclusions These data demonstrate that the absence of mast cells exacerbate radiation enteropathy by mechanisms that likely involve the coagulation system, anti-inflammatory cytokine signaling, and the innate immune system; and that these mechanisms are regulated by PEA in a mast cell-dependent manner. The endocannabinoid system should be explored as target for mitigating intestinal radiation injury. PMID:24848354

  11. Acute Pseudohepatitis in a Chronic Substance Abuser Secondary to Occult Seat Belt Injury

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    Eric CS Lam

    1999-01-01

    Full Text Available Causes of a massive elevation in serum aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] in the substance-abusing patient include viral hepatitis and drug hepatotoxicity. A patient chronically addicted to injection heroin and cocaine presented to the emergency room in a confused state and was admitted to a medical ward with an AST of 4120 U/L, ALT 3820 U/L and right upper quadrant discomfort. Investigations for viral and hepatotoxic causes for the liver dysfunction revealed only hepatitis C seropositivity. A computed tomogram of the abdomen, however, revealed a significant contusion to the right lobe of the liver consistent with traumatic injury. A motor vehicle accident, in which the patient was wearing a seat belt, and which had occurred a few days before admission and had been thought to be minor, was the cause of the liver dysfunction. Significant blunt abdominal traumatic injuries are usually managed exclusively by surgical trauma units. This case underlines the need for medical specialists to be aware of hepatic contusion injuries and to have a high index of suspicion when investigating unexplained hepatocellular dysfunction in chronic substance abusers who have been in motor vehicle accidents.

  12. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-04-01

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis.

  13. DIETARY FLAXSEED PREVENTS RADIATION-INDUCED OXIDATIVE LUNG DAMAGE, INFLAMMATION AND FIBROSIS IN A MOUSE MODEL OF THORACIC RADIATION INJURY

    Science.gov (United States)

    Lee, James C.; Krochak, Ryan; Blouin, Aaron; Kanterakis, Stathis; Chatterjee, Shampa; Arguiri, Evguenia; Vachani, Anil; Solomides, Charalambos C.; Cengel, Keith A.; Christofidou-Solomidou, Melpo

    2009-01-01

    Flaxseed (FS) has high contents of omega-3 fatty acids and lignans with antioxidant properties. Its use in preventing thoracic X-ray radiation therapy (XRT)-induced pneumonopathy has never been evaluated. We evaluated FS supplementation given to mice given before and post-XRT. FS-derived lignans, known for their direct antioxidant properties, were evaluated in abrogating ROS generation in cultured endothelial cells following gamma radiation exposure. Mice were fed 10% FS or isocaloric control diet for three weeks and given 13.5 Gy thoracic XRT. Lungs were evaluated at 24 hours for markers of radiation-induced injury, three weeks for acute lung damage (lipid peroxidation, lung edema and inflammation), and at four months for late lung damage (inflammation and fibrosis). FS-Lignans blunted ROS generation in vitro, resulting from radiation in a dose-dependent manner. FS-fed mice had reduced expression of lung injury biomarkers (Bax, p21, and TGF-beta1) at 24 hours following XRT and reduced oxidative lung damage as measured by malondialdehyde (MDA) levels at 3 weeks following XRT. In addition, FS-fed mice had decreased lung fibrosis as determined by hydroxyproline content and decreased inflammatory cell influx into lungs at 4 months post XRT. Importantly, when Lewis Lung carcinoma cells were injected systemically in mice, FS dietary supplementation did not appear to protect lung tumors from responding to thoracic XRT. Dietary FS is protective against pulmonary fibrosis, inflammation and oxidative lung damage in a murine model. Moreover, in this model, tumor radioprotection was not observed. FS lignans exhibited potent radiation-induced ROS scavenging action. Taken together, these data suggest that dietary flaxseed may be clinically useful as an agent to increase the therapeutic index of thoracic XRT by increasing the radiation tolerance of lung tissues. PMID:18981722

  14. Functional electrical stimulation therapy improves grasping in chronic cervical spinal cord injury: Two case studies

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    Miller Rosalynn C.

    2008-01-01

    Full Text Available OBJECTIVE AND IMPORTANCE: To present case studies of two individuals with chronic cervical spinal cord injury (SCI who participated in functional electrical stimulation (FES therapy with the objective to restore voluntary grasp function. CLINICAL PRESENTATION: Both individuals (right hand dominant males, age 24 and 31 had a sustained a cervical SCI (C6 and C4-5, respectively at least 8 years prior to participation in this study. INTERVENTION: Both individuals participated in an individualized FES therapy program for 6 weeks. FES therapy was administered through a regimen of three, one-hour sessions, per week for three months. A single arm of each participant (n = 2 was treated. FES therapy is an integrative intervention strategy combining muscle strengthening, functional movement training and stretching. The participant's hand movement abilities were assessed pre and post FES therapy using the Manual Muscle Test (MMT, a modified Sollerman Hand Function Test (mSHFT, and the Reach, Grasp, Transport and Release Task (RGTR. DISCUSSION: As the injuries of participants in the current study were chronic and thus neurologically stable, no spontaneous improvements/recovery in hand function was expected. However, FES as part of an integrated therapeutic approach affected restoration and improvement of hand function in both participants. CONCLUSION: The concurrent improvement in strength, integrated motor function and object contact following FES therapy, demonstrated that there is potential for affecting change in hand function of individuals with chronic SCI.

  15. Late radiation injury of the colon and rectum. Surgical management and outcome

    Energy Technology Data Exchange (ETDEWEB)

    Kimose, H.H.; Fischer, L.; Spjeldnaes, N.; Wara, P. (Aarhus Municipal Hospital (Denmark))

    1989-08-01

    After a median latency of 2 years, the initial late colorectal radiation injuries in 182 patients were: stricture (37 percent), minor lesions (36 percent), rectovaginal fistula (22 percent), and gangrene or other fistulas (5 percent). Due to progression, new colorectal injuries, primarily stricture (55 percent) and fistula (42 percent), occurred in 68 patients (37 percent). Resection provided the best results. However, the resectability rate was low (46 percent) and resection was primarily performed in patients with a circumscript well-defined stricture of the proximal rectum or sigmoid colon with an anastomotic leakage rate of 5 percent. The prevailing management of 78 patients with fistula or stricture with synchronous fistula was defunctioning colostomy, primarily end-sigmoidostomy, providing fair results in half of the patients. Stomal complications occurred in 15 percent. The radiation-induced colorectal mortality was 8 percent. Colorectal fistula and associated radiation injuries of the urinary tract, and especially of the small bowel, were the major determinants of fatal outcome, yielding an overall radiation-induced mortality of 25 percent. After a median observation time of 13 years, half of the patients were alive at follow-up; 56 percent of these had a fair outcome whereas the remaining patients continued to have mild symptoms responding to conservative measures (34 percent) or disabling symptoms (10 percent).

  16. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

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    Janaína Garcia Gonçalves

    Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

  17. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

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    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract Objective Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  18. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

    Full Text Available Objective: Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries.Method:This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment.Results:Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion:Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  19. Protective effects of emodin and astragalus polysaccharides on chronic hepatic injury in rats

    Institute of Scientific and Technical Information of China (English)

    DANG Shuang-suo; ZHANG Xin; JIA Xiao-li; CHENG Ya-nan; SONG Ping; LIU En-qi; HE Qian; LI Zong-fang

    2008-01-01

    Background Chinese medicine plays an important role in hepatoprotective treatment. This study was conducted to investigate the protective effects of emodin and astragalus polysaccharides (APS) in a rat model of chronic hepatic injury.Methods Chronic hepatic injury was induced by hypodermic injection of an olive oil solution containing 40% carbon tetrachloride (CCI4) twice a week, in addition to a diet of 79.5% maizena, 20% fat, 0.5% cholesterol, and 10% alcohol in the drinking water ad libitum for 12 weeks. Meanwhile, the rats were exposed to different concentrations of emodin (40 mg·kg-1·d-1), APS (200 mg·kg-1·d-1), combination drug (emodin 40 mg.kg-1·d-1 combined with APS 200 mg.kg-1·d-1) and colchicine (0.1 mg·kg-1·d-1) in parallel by oral gavage (once a day for 12 weeks). At the end of 12 weeks, blood serum and liver tissue were taken. Serum was collected to determine the levels of total bilirubin (TBIL), alanine transaminase (ALT),aspartate transaminose (AST), and albumin (ALB). Liver and spleen indexes were assayed, followed by the measurements of the liver associated enzyme superoxide dismutase (SOD) and malondialdehyde (MDA). Histopathological changes were studied using optical microscopy.Results Splenohepatomegalia was alleviated and serum levels of TBIL and ALT were reduced in the groups treated with emodin and APS when compared to the control group. In addition, the ALB level in the APS and combination groups was higher. Similarly, the SOD activity of liver homogenates was significantly higher in the groups treated with emodin and APS, while administration of the herbal derivatives prevented the elevation in MDA levels. Histological analysis showed that the APS and combination groups significantly ameliorated the hepatic injury.Conclusions Co-administration of emodin and APS demonstrated a synergistic action in reducing ALT and restoring ALB in the serum from a rat model of chronic hepatic injury. Emodin and APS may ameliorate the CCI4-induced

  20. Early Stage of Chronic Kidney Disease with Renal Injury Caused by Hypertension in a Dog

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    Akira Yabuki

    2011-01-01

    Full Text Available A 10-year-old spayed female Papillon weighing 4.0 kg presented with a history of persistent hematuria and pollakiuria. Concurrent bladder calculi, a mammary gland tumor, and nonazotemic early stage of chronic kidney disease with contracted kidneys were noted in this dog. The dog underwent cystectomy, unilateral mastectomy, and intraoperative renal biopsy. On the basis of histopathological analysis of renal biopsy results, it was suspected that renal injury of the dog was caused by persistent hypertension, and a follow-up examination revealed severe hypertension. The dog was treated with a combination of an angiotensin-converting enzyme inhibitor and calcium channel blocker. The treatment produced a good outcome in the dog, and there has been no progression of the chronic kidney disease for over 2 years.

  1. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury

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    John Williamson

    2015-07-01

    Full Text Available The use of a modified Facial Affect Recognition (FAR training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years traumatic brain injury (TBI.  The modified FAR training was administered via telepractice to target social communication skills.  Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-play.  Pre- and post-therapy measures included static facial photos to identify emotion and the Prutting and Kirchner Pragmatic Protocol for social communication.  Both participants with chronic TBI showed gains on identifying facial emotions on the static photos.               

  2. Surgical treatment of radiation injuries of the colon and rectum

    Energy Technology Data Exchange (ETDEWEB)

    Jao, S.W.; Beart, R.W. Jr.; Gunderson, L.L.

    1986-02-01

    Between 1950 and 1983, radiation-induced proctitis was diagnosed proctoscopically in 720 patients at the Mayo Clinic. Sixty-two patients with severe colorectal symptoms were treated surgically. The interval from cessation of radiotherapy to onset of symptoms ranged from 3 weeks to 24 months (mean 33 months). The 62 patients underwent a total of 143 operations with 8 operative deaths (13 percent), and 40 patients (65 percent) had 61 complications. The morbidity rate was lower after colostomy alone (44 percent in 27 patients) than after more aggressive operations (80 percent in 35 patients). Transverse loop colostomy and descending colostomy were safer than sigmoid colostomy. The dissection adhesions, opening of tissue planes, and careless manipulation of intestine may result in necrosis and perforation of the intestine, bladder, or vaginal wall; these were the main causes of fecal and other internal fistulas in our study.

  3. Behavior, physiology, and energy deposition in rats chronically exposed to 2450-MHz radiation

    Energy Technology Data Exchange (ETDEWEB)

    D' Andrea, J.A.; Gandhi, O.P.

    1987-11-01

    The research program was initiated to determine both the specific absorption rate (SAR) and the behavioral and physiological consequences of chronic c-w microwave radiation exposure at 2450 MHz in the laboratory rat. Whole-body average and local SARs at discrete sites within the body of rats and mice were determined experimentally using different exposure systems and analytical techniques. The whole-body average SAR and the distribution of SAR within the body depends on a variety of factors: type of exposure system, polarization of the field, size of the animal, and angle of radiation incident on the body. Three experiments were conducted to determine the effects of chronic exposure to 2450-MHz microwave radiation on several measures of rat behavior and physiology. Groups of rats were exposed intermittently to 2450-MHz radiation at power densities of 0.5 mW/sq. cm. or 2.5 mW/sq. cm. for 90 days.

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

    Science.gov (United States)

    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. Nd: YAG laser therapy of rectosigmoid bleeding due to radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Leuchter, R.S.; Petrilli, E.S.; Dwyer, R.M.; Hacker, N.F.; Castaldo, T.W.; Lagasse, L.D.

    1982-06-01

    The Nd:YAG laser was used to treat a patient bleeding from the rectosigmoid as a result of radiation injury related to therapy for cervical carcinoma. Successful laser therapy was performed after a diverting colostomy failed to control persistent bleeding. Further surgical procedures were not required. Characteristics of Nd:YAG laser as compared with those of the carbon dioxide and argon lasers are considered.

  6. YKL-40 expression in CD14+ liver cells in acute and chronic injury

    Institute of Scientific and Technical Information of China (English)

    Oscar Pizano-Martínez; Vidal Delgado-Rizo; Irinea Ya(n)ez-Sánchez; Pilar Alatorre-Carranza; Alejandra Miranda-Díaz; Pablo C Ortiz-Lazareno; Trinidad García-Iglesias; Adrian Daneri-Navarro; Mónica Vázquez-Del Mercado; Mary Fafutis-Morris

    2011-01-01

    AIM: To demonstrate that CD14+ cells are an important source of the growth factor YKL-40 in acute and chronic liver damage.METHODS: Rats were inoculated with one dose of CCl4 to induce acute damage. Liver biopsies were obtained at 0, 6, 12, 24, 48 and 72 h. For chronic damage, CCl4 was administered three days per week for 6 or 8 wk. Tissue samples were collected, and cellular populations were isolated by liver digestion and purified by cell sorting. YKL-40 mRNA and protein expression were evaluated by real-time polymerase chain reaction and western blot. RESULTS: Acute liver damage induced a rapid increase of YKL-40 mRNA beginning at 12 h. Expression peaked at 24 h, with a 26-fold increase over basal levels. By 72 h however, YKL-40 expression levels had nearly returned to control levels. On the other hand, chronic damage induced a sustained increase in YKL-40 expression, with 7- and 9-fold higher levels at 6 and 8 wk, respectively. The pattern of YKL-40 expression in different subpopulations showed that CD14+ cells, which include Kupffer cells, are a source of YKL-40 after acute damage at 72 h [0.09 relative expression units (REU)] as well as after chronic injury at 6 wk (0.11 REU). Hepatocytes, in turn, accounted for 0.06 and 0.01 REU after 72 h (acute) or 6 wk (chronic), respectively. The rest of the CD14- cells (including T lymphocytes, B lymphocytes, natural killer and natural killer T cells) yielded 0.07 and 0.15 REU at 72 h and 6 wk, respectively. YKL-40 protein expression in liver was detected at 72 h as well as 6 and 8 wk, with the highest expression relative to controls (11-fold; P ≤ 0.05) seen at 6 wk. Macrophages were stimulated by lipopolysaccharide. We demonstrate that under these conditions, these cells showed maximum expression of YKL-40 at 12 h, with P < 0.05 compared with controls.CONCLUSION: Hepatic CD14+ cells are an YKL-40 mRNA and protein source in acute and chronic liver injury, with expression patterns similar to growth factors implicated

  7. Functional Recovery in Chronic Stage of Spinal Cord Injury by Neurorestorative Approach: A Case Report

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    Alok Sharma

    2014-01-01

    Full Text Available Spinal cord injury (SCI at an early age can be debilitating for the child’s growth. Current treatments show a level of stagnancy, after which the recovery is minimal. Cellular therapy is an emerging area of research and has been found to possess many benefits in the previous studies. Transplantation of autologous bone marrow mononuclear cells (BMMNCs has demonstrated therapeutic potential for many neurological conditions, including spinal cord injury. Here we report a case of 6-year-old girl with traumatic SCI at the level of C7-D1 4 years back, who underwent 2 doses of cell transplantation with autologous BMMNCs with an interval of 6 months along with standard rehabilitation. The patient did not have any major or minor side effects. The patient showed clinical improvements throughout the 6 months after transplantation, which was assessed using Functional Independence Measure (before: 82, after: 101 out of 126. There were patchy areas of sensory gain in bilateral feet recorded, with improvements in the bladder sensation and control. Improved gait was seen as a result of better strength in abdominals and back extensors. The fact that there was functional improvement in the chronic plateau phase indicates the potential of cell therapy in chronic SCI. Further clinical studies are warranted.

  8. Chronic abdominal pain in long-term spinal cord injury: a follow-up study

    DEFF Research Database (Denmark)

    Nielsen, Steffen D; Faaborg, Pia Møller; Christensen, Peter

    2017-01-01

    -reported constipation. The median intensity (numeric rating scale) was 6.0 (range 3-10) and it was often associated with autonomic symptoms. Nine (8%) of the 115 individuals who responded in both 2006 and 2015 had developed new abdominal pain or discomfort, 30 (26%) no longer reported it, and 28 (24%) reported......A longitudinal postal survey was carried to evaluate the prevalence and characteristics of abdominal pain in long-term spinal cord injury (SCI). In 2006, a questionnaire on chronic abdominal pain and discomfort was sent to the 284 members of the Danish SCI association who had been members...... abdominal pain. The mean time since injury was 30.5 (9.8) years. Chronic abdominal pain or discomfort was reported by 32.8% (41/125), and 23% (29/125) of responders had been at least moderately bothered by this in the past week. Abdominal pain or discomfort was more common in women and in those with self...

  9. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  10. Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept

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    David L. Bolduc

    2014-01-01

    Full Text Available Multivariate radiation injury estimation algorithms were formulated for estimating severe hematopoietic acute radiation syndrome (H-ARS injury (i.e., response category three or RC3 in a rhesus monkey total-body irradiation (TBI model. Classical CBC and serum chemistry blood parameters were examined prior to irradiation (d 0 and on d 7, 10, 14, 21, and 25 after irradiation involving 24 nonhuman primates (NHP (Macaca mulatta given 6.5-Gy 60Co Υ-rays (0.4 Gy min−1 TBI. A correlation matrix was formulated with the RC3 severity level designated as the “dependent variable” and independent variables down selected based on their radioresponsiveness and relatively low multicollinearity using stepwise-linear regression analyses. Final candidate independent variables included CBC counts (absolute number of neutrophils, lymphocytes, and platelets in formulating the “CBC” RC3 estimation algorithm. Additionally, the formulation of a diagnostic CBC and serum chemistry “CBC-SCHEM” RC3 algorithm expanded upon the CBC algorithm model with the addition of hematocrit and the serum enzyme levels of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. Both algorithms estimated RC3 with over 90% predictive power. Only the CBC-SCHEM RC3 algorithm, however, met the critical three assumptions of linear least squares demonstrating slightly greater precision for radiation injury estimation, but with significantly decreased prediction error indicating increased statistical robustness.

  11. Effects of sodium citrate on salt sensitivity and kidney injury in chronic renal failure.

    Science.gov (United States)

    Kim, Sejoong; Yang, Jin Young; Jung, Eun Sook; Lee, Jeonghwan; Heo, Nam Ju; Lee, Jae Wook; Na, Ki Young; Han, Jin Suk

    2014-12-01

    Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

  12. A case of radiation pulmonary injury simulating bronchiolitis obliterans organizing pneumonia following postoperative radiotherapy for breast cancer

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    Katoh, Toshiyuki; Iwata, Masaru; Yoshida, Norio; Katagiri, Akira; Takeda, Naoya [Kariya General Hospital, Aichi (Japan)

    2001-09-01

    A 57-year-old female underwent conservative surgery for a left sided breast cancer, and received 48 Gy postoperative radiation therapy. One year later, a chest CT scan disclosed bilateral patchy ground glass opacities. She had no subjective symptom. These abnormal opacities disappeared spontaneously without any treatment. We considered this was a radiation lung injury simulating bronchiolitis obliterans organizing pneumonia. We emphasize that the symptomless and spontaneous resolution of this type of lung injury should be kept is mind. (author)

  13. Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis.

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    Chen, Jinglou; Du, Lifen; Li, Jingjing; Song, Hongping

    2016-10-01

    Cadmium (Cd) pollution is a serious environmental problem. Kidney is a main target organ of Cd toxicity. This study was undertaken to investigate the potential protective effects of epigallocatechin-3-gallate (EGCG) against chronic renal injury and fibrosis induced by CdCl2. Rat model was induced by exposing to 250 mg/L CdCl2 through drinking water. The renal function was evaluated by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (SCR). The oxidative stress was measured by detecting the levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione/oxidized glutathione (GSH/GSSG) and renal enzymatic antioxidant status. Additionally, the renal levels of transforming growth factor-β1 (TGF-β1), Smad3, phosphorylation-Smad3 (pp-Smad3), α-smooth muscle actin (α-SMA), vimentin and E-cadherin were measured by western blot assay. Renal levels of microRNA-21 (miR-21), miR-29a/b/c and miR-192 were measured by quantitative RT-PCR. It was found that EGCG ameliorated the CdCl2-induced renal injury, inhibited the level of oxidative stress, normalized renal enzymatic antioxidant status and E-cadherin level, as well as attenuated the over generation of TGF-β1, pp-Smad3, vimentin and α-SMA. EGCG also decreased the production of miR-21 and miR-192, and enhanced the levels of miR-29a/b/c. These results showed that EGCG could attenuate Cd induced chronic renal injury.

  14. A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

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    Jianhong Ye

    Full Text Available PURPOSE: To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC patients. METHODS AND MATERIALS: Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs, internal carotid arteries (ICAs and basal artery (BA were estimated through Transcranial Color Doppler (TCD. The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. RESULTS: Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05. IMT had positive correlation with post radiation interval (p = 0.049. Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001. Plaques were more common in patients with TLN than patients without TLN (p = 0.038. In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001. Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001. CONCLUSION: Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

  15. The MET Receptor Tyrosine Kinase Confers Repair of Murine Pancreatic Acinar Cells following Acute and Chronic Injury

    Science.gov (United States)

    Gaziova, Ivana; Jackson, Daniel; Boor, Paul J.; Carter, Dwayne; Cruz-Monserrate, Zobeida; Elferink, Cornelis J.; Joshi, Aditya D.; Kaphalia, Bhupendra; Logsdon, Craig D.; Pereira de Castro, Karen; Soong, Lynn; Tao, Xinrong; Qiu, Suimin; Elferink, Lisa A.

    2016-01-01

    Acinar cells represent the primary target in necroinflammatory diseases of the pancreas, including pancreatitis. The signaling pathways guiding acinar cell repair and regeneration following injury remain poorly understood. The purpose of this study was to determine the importance of Hepatocyte Growth Factor Receptor/MET signaling as an intrinsic repair mechanism for acinar cells following acute damage and chronic alcohol-associated injury. Here, we generated mice with targeted deletion of MET in adult acinar cells (MET-/-). Acute and repetitive pancreatic injury was induced in MET-/- and control mice with cerulein, and chronic injury by feeding mice Lieber-DeCarli diets containing alcohol with or without enhancement of repetitive pancreatic injury. We examined the exocrine pancreas of these mice histologically for acinar death, edema, inflammation and collagen deposition and changes in the transcriptional program. We show that MET expression is relatively low in normal adult pancreas. However, MET levels were elevated in ductal and acinar cells in human pancreatitis specimens, consistent with a role for MET in an adaptive repair mechanism. We report that genetic deletion of MET in adult murine acinar cells was linked to increased acinar cell death, chronic inflammation and delayed recovery (regeneration) of pancreatic exocrine tissue. Notably, increased pancreatic collagen deposition was detected in MET knockout mice following repetitive injury as well alcohol-associated injury. Finally, we identified specific alterations of the pancreatic transcriptome associated with MET signaling during injury, involved in tissue repair, inflammation and endoplasmic reticulum stress. Together, these data demonstrate the importance of MET signaling for acinar repair and regeneration, a novel finding that could attenuate the symptomology of pancreatic injury. PMID:27798657

  16. Diffusion tensor imaging detects chronic microstructural changes in white and grey matter after traumatic brain injury in rat

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    Teemu eLaitinen

    2015-04-01

    Full Text Available Traumatic brain injury (TBI is a major cause of disability and death in people of all ages worldwide. An initial brain injury caused by external mechanical forces triggers a cascade of tissue changes that lead to a wide spectrum of symptoms and disabilities, such as cognitive deficits, mood or anxiety disorders, motor impairments, chronic pain, and epilepsy. We investigated the detectability of secondary injury at a chronic time-point using ex vivo diffusion tensor imaging (DTI in a rat model of TBI, lateral fluid percussion injury. Our analysis of ex vivo DTI data revealed persistent microstructural tissue changes in white matter tracts, such as the splenium of the corpus callosum, angular bundle, and internal capsule. Histologic examination revealed mainly loss of myelinated axons and/or iron accumulation. Grey matter areas in the thalamus exhibited an increase in fractional anisotropy associated with neurodegeneration, myelinated fiber loss, and/or calcifications at the chronic phase. In addition, we examined whether these changes could also be detected with in vivo settings at the same chronic time-point. Our results provide insight into DTI detection of microstructural changes in the chronic phase of TBI, and elucidate how these changes correlate with cellular level alterations. These findings suggest that DTI could be a useful tool for detecting potential imaging biomarkers after TBI as indicators of progressive damage or recovery

  17. [Endolacunar laser radiation of the tonsils in conservative treatment of chronic tonsillitis].

    Science.gov (United States)

    Staroverova, T K; Shul'diakov, V A; Raĭgorodskiĭ, Iu M; Tatarenko, D A

    2007-01-01

    Vegetative and immune system indices, clinical symptoms of chronic tonsillitis exacerbation were compared in laser radiation of the tonsils with two methods - surface pharyngeal and endolacunar. The results show that under endolacunar method the symptoms regress 1.46 times faster, the number of late exacerbations decrease 1.5-2-fold.

  18. Twitch and tetanic properties of human thenar motor units paralyzed by chronic spinal cord injury.

    Science.gov (United States)

    Häger-Ross, C K; Klein, C S; Thomas, C K

    2006-07-01

    Little is known about how human motor units respond to chronic paralysis. Our aim was to record surface electromyographic (EMG) signals, twitch forces, and tetanic forces from paralyzed motor units in the thenar muscles of individuals (n = 12) with chronic (1.5-19 yr) cervical spinal cord injury (SCI). Each motor unit was activated by intraneural stimulation of its motor axon using single pulses and trains of pulses at frequencies between 5 and 100 Hz. Paralyzed motor units (n = 48) had small EMGs and weak tetanic forces (n = 32 units) but strong twitch forces, resulting in half-maximal force being achieved at a median of only 8 Hz. The distributions for cumulative twitch and tetanic forces also separated less for paralyzed units than for control units, indicating that increases in stimulation frequency made a smaller relative contribution to the total force output in paralyzed muscles. Paralysis also induced slowing of conduction velocities, twitch contraction times and EMG durations. However, the elevated ratios between the twitch and the tetanic forces, but not contractile speed, correlated significantly with the extent to which unit force summated in response to different frequencies of stimulation. Despite changes in the absolute values of many electrical and mechanical properties of paralyzed motor units, most of the distributions shifted uniformly relative to those of thenar units obtained from control subjects. Thus human thenar muscles paralyzed by SCI retain a population of motor units with heterogeneous contractile properties because chronic paralysis influenced all of the motor units similarly.

  19. Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2.

    Science.gov (United States)

    Nissenbaum, Jonathan; Devor, Marshall; Seltzer, Ze'ev; Gebauer, Mathias; Michaelis, Martin; Tal, Michael; Dorfman, Ruslan; Abitbul-Yarkoni, Merav; Lu, Yan; Elahipanah, Tina; delCanho, Sonia; Minert, Anne; Fried, Kaj; Persson, Anna-Karin; Shpigler, Hagai; Shabo, Erez; Yakir, Benjamin; Pisanté, Anne; Darvasi, Ariel

    2010-09-01

    Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca(2+) channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments.

  20. Extracorporeal shock wave therapy for painful chronic neurogenic heterotopic ossification after traumatic brain injury: a case report.

    Science.gov (United States)

    Choi, Yong Min; Hong, Seok Hyun; Lee, Chang Hyun; Kang, Jin Ho; Oh, Ju Sun

    2015-04-01

    Neurogenic heterotopic ossification (NHO) is a process of benign bone formation and growth in soft tissues surrounding major synovial joints and is associated with central nervous system (CNS) injuries. It is a common complication in major CNS injuries, such as traumatic brain injury, spinal cord injury, and stroke. Here, we report the case of a 72-year-old male, who experienced a traumatic brain injury and painful chronic NHO around the left hip joint. Three applications of extracorporeal shock wave therapy (ESWT) were administered to the area of NHO, which resulted in pain relief and an improvement in the loss of motion in the left hip joint. Improvements were also noted in walking performance and activities of daily living, although the size of NHO remained unchanged. Therapeutic effects of ESWT lasted for 12 weeks.

  1. Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122.

    Science.gov (United States)

    van der Meer, A J; Farid, W R R; Sonneveld, M J; de Ruiter, P E; Boonstra, A; van Vuuren, A J; Verheij, J; Hansen, B E; de Knegt, R J; van der Laan, L J W; Janssen, H L A

    2013-03-01

    As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte-derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte-derived miR-122 and miR-192 were analysed in sera of 102 chronic HCV-infected patients and 24 healthy controls. Serum levels of miR-122 and miR-192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P chronic HCV infection (P = 0.026). Importantly, miR-122 was also superior in discriminating chronic HCV-infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte-derived microRNAs in circulation and demonstrated that in particular miR-122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.

  2. Repeated Closed Head Injury in Mice Results in Sustained Motor and Memory Deficits and Chronic Cellular Changes.

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    Amanda N Bolton Hall

    Full Text Available Millions of mild traumatic brain injuries (TBIs occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at 48h intervals, or five sham injuries at 24h intervals were evaluated across a 10 week period after injury. Animals with repeated CHI exhibited motor coordination and memory deficits, but not gait abnormalities when compared to sham animals. At 10wks post-injury, no notable neuron loss or glial reactivity was observed in the cortex, hippocampus, or corpus callosum. Argyrophilic axons were found in the pyramidal tract of some injured animals, but neither silver stain accumulation nor inflammatory responses in the injury groups were statistically different from the sham group in this region. However, argyrophilic axons, microgliosis and astrogliosis were significantly increased within the optic tract of injured animals. Repeated mild CHI also resulted in microgliosis and a loss of neurofilament protein 200 in the optic nerve. Lengthening the inter-injury interval from 24h to 48h did not effectively reduce these behavioral or cellular responses. These results suggest that repeated mild CHI results in persistent behavioral dysfunction and chronic pathological changes within the visual system, neither of which was significantly attenuated by lengthening the inter-injury interval from 24h to 48h.

  3. Altered activation patterns by triceps surae stretch reflex pathways in acute and chronic spinal cord injury.

    Science.gov (United States)

    Frigon, Alain; Johnson, Michael D; Heckman, C J

    2011-10-01

    Spinal reflexes are modified by spinal cord injury (SCI) due the loss of excitatory inputs from supraspinal structures and changes within the spinal cord. The stretch reflex is one of the simplest pathways of the central nervous system and was used presently to evaluate how inputs from primary and secondary muscle spindles interact with spinal circuits before and after spinal transection (i.e., spinalization) in 12 adult decerebrate cats. Seven cats were spinalized and allowed to recover for 1 mo (i.e., chronic spinal state), whereas 5 cats were evaluated before (i.e., intact state) and after acute spinalization (i.e., acute spinal state). Stretch reflexes were evoked by stretching the left triceps surae (TS) muscles. The force evoked by TS muscles was recorded along with the activity of several hindlimb muscles. Stretch reflexes were abolished in the acute spinal state due to an inability to activate TS muscles, such as soleus (Sol) and lateral gastrocnemius (LG). In chronic spinal cats, reflex force had partly recovered but Sol and LG activity remained considerably depressed, despite the fact that injecting clonidine could recruit these muscles during locomotor-like activity. In contrast, other muscles not recruited in the intact state, most notably semitendinosus and sartorius, were strongly activated by stretching TS muscles in chronic spinal cats. Therefore, stretch reflex pathways from TS muscles to multiple hindlimb muscles undergo functional reorganization following spinalization, both acute and chronic. Altered activation patterns by stretch reflex pathways could explain some sensorimotor deficits observed during locomotion and postural corrections after SCI.

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

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    Daojiang Yu

    2016-10-01

    Full Text Available 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.

  5. Pharmacological correlation between the formalin test and the neuropathic pain behavior in different species with chronic constriction injury.

    NARCIS (Netherlands)

    Vissers, K.C.P.; Geenen, F.; Biermans, R.; Meert, T.F.

    2006-01-01

    Research on mechanisms of drug action, and preclinical screening of molecules with a potential activity on neuropathic pain requires extensive animal work. The chronic constriction injury model is one of the best-characterized models of neuropathic pain behavior in rats, but requires extensive time

  6. Functional Magnetic Resonance Imaging of Chronic Dysarthric Speech after Childhood Brain Injury: Reliance on a Left-Hemisphere Compensatory Network

    Science.gov (United States)

    Morgan, Angela T.; Masterton, Richard; Pigdon, Lauren; Connelly, Alan; Liegeois, Frederique J.

    2013-01-01

    Severe and persistent speech disorder, dysarthria, may be present for life after brain injury in childhood, yet the neural correlates of this chronic disorder remain elusive. Although abundant literature is available on language reorganization after lesions in childhood, little is known about the capacity of motor speech networks to reorganize…

  7. Gonadectomy affects brain derived neurotrophic factor in rats after chronic constriction nerve injury

    Institute of Scientific and Technical Information of China (English)

    Xin ZHAO; Xin WANG; Shu-yun ZHENG; Jian-guo XU

    2004-01-01

    AIM: To assess the effect of gonadectomy on brain derived neurotrophic factor (BDNF) expression in neuropathic pain. METHODS: Using chronic constriction injury (CCI) model, we detected BDNF mRNA in dorsal root ganglion and protein content in spinal cord by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay respectively. The time point we chose was post CCI operation d 0, 3, 7, 14, and 21.RESULTS: After CCI surgery, BDNF mRNA in ipsilateral DRGs was upregulated and reached its maximum on post operation d 7. BDNF protein level in ipsilateral spinal cord was also increased and reached its maximum on post operation d 14. The magnitude of this increase in gonadectomy (GDX) rats was significantly smaller than the GDX-sham rats at each time point. CONCLUSION: Gonadectomy reduced the BDNF increment after CCI surgery.Estrogen may affect nociceptive processing by its effect on BDNF.

  8. Intestinal microbiota-kidney cross talk in acute kidney injury and chronic kidney disease.

    Science.gov (United States)

    Noel, Sanjeev; Martina-Lingua, Maria N; Bandapalle, Samatha; Pluznick, Jennifer; Hamad, Abdel Rahim A; Peterson, Daniel A; Rabb, Hamid

    2014-01-01

    The pathophysiology of acute kidney injury (AKI) involves multiple and overlapping immunological, biochemical, and hemodynamic mechanisms that modulate the effects of both the initial insult and the subsequent repair. Limited but recent experimental data have revealed that the intestinal microbiota significantly affects outcomes in AKI. Additional evidence shows significant changes in the intestinal microbiota in chronic kidney disease patients and in experimental AKI. In this minireview, we discuss the current status of the effect of intestinal microbiota on kidney diseases, the immunomodulatory effects of intestinal microbiota, and the potential mechanisms by which microbiota can modify kidney diseases and vice versa. We also propose future studies to clarify the role of intestinal microbiota in kidney diseases and to explore how the modification of gut microbiota may be a potential therapeutic tool.

  9. Antiallodynic Effect of Herbal Medicine Yokukansan on Peripheral Neuropathy in Rats with Chronic Constriction Injury

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    Yasuyuki Suzuki

    2012-01-01

    Full Text Available Yokukansan, one of the traditional Japanese herbal medicines, ameliorated neuropathic pain symptoms in patients. In this study, we investigated the effects of yokukansan on neuropathic pain in chronic constriction injury (CCI model. Oral administration of yokukansan significantly inhibited mechanical and cold allodynia in the von Frey hair or acetone test, respectively. In comparison, amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not significant, antiallodynic effects in the mechanical and cold tests. Yokukansan significantly inhibited the cerebrospinal fluid dialysate level of glutamate that had increased by the stimulation of brush or acetone. Glutamate transporter inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that yokukansan was confirmed to have antiallodynic effects in CCI rats, which are related to a blockade of glutamatergic neurotransmission via activation of glutamate transporters in the spinal cord.

  10. Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.

    Science.gov (United States)

    Kim, Hyun Jee

    2015-08-01

    The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model.

  11. Modeling hematopoietic system response caused by chronic exposure to ionizing radiation.

    Science.gov (United States)

    Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akleyev, Alexander V; Yashin, Anatoly I

    2011-05-01

    A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, erythrocytes, and platelets). The required model parameters were estimated based on available results of human and experimental animal studies. They include the steady-state number of hematopoietic stem cells and peripheral blood cell lines in an unexposed organism, amplification parameters for each blood line, parameters describing proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity related to cell death and non-lethal cell damage. The model predictions were tested using data on hematological measurements (e.g., blood counts) performed in 1950-1956 in the Techa River residents chronically exposed to ionizing radiation since 1949. The suggested model of hematopoiesis is capable of describing experimental findings in the Techa River Cohort, including: (1) slopes of the dose-effect curves reflecting the inhibition of hematopoiesis due to chronic ionizing radiation, (2) delay in effect of chronic exposure and accumulated character of the effect, and (3) dose-rate patterns for different cytopenic states (e.g., leukopenia, thrombocytopenia).

  12. Chronic low-dose radiation protects cells from high-dose radiation via increase of AKT expression by NF-{sub k}B

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    Park, Hyung Sun; Seong, Ki Moon; Kim, Ji Young; Kim, Cha Soon; Yang, Kwang Hee; Nam, Seon Young [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., LTD., Gyeongju (Korea, Republic of)

    2013-04-15

    Exposure to low-dose and low-dose rate of ionizing radiation is an important issue in radiation protection. Low-dose ionizing radiation has been observed to elicit distinctly different responses compared to high-dose radiation, in various biological systems including the reproductive, immune, and hematopoietic systems (Liu et al. 2006). Some data were reported that low-dose radiation could initiate beneficial effects by stimulating cell growth, DNA repair, activation of transcription factors and gene expression (Calabrese et al., 2004). Cells exposed to low-dose radiation can develop adaptive resistance to subsequent high-dose radiation induced DNA damage, gene mutation, and cell death. We previously reported that low-dose of ionizing radiation induced cell survival through the activation of AKT (protein kinase B, PKB) pathway (Park et al., 2009). AKT has been shown to be potently activated in response to a wide variety of growth factors and ionizing radiation. Cell survival against ionizing radiation seems to be associated with the activation of AKT pathway via phosphorylation of its downstream nuclear target molecules. In the present study, we examined the effects of chronic low-dose irradiation in human lung fibroblast cells. The aim was to explore the possibility of a low-dose radiation-induced adaptive cellular response against subsequent challenging high-dose irradiation. In the present study, we examined the regulatory mechanism responsible for cellular response induced by chronic low-dose of ionizing radiation in normal human cells. We found that the level of AKT protein was closely associated with cell survival. In addition, NF-{sub k}B activation by chronic low-dose radiation regulates AKT activation via gene expression and acinus expression. In conclusion, our data demonstrate that chronic low-dose radiation could inhibit the cell death induced by cytotoxic high-dose radiation through the modulation of the level of AKT and acinus proteins via NF-{sub k

  13. The value of multimodal magnetic resonance imaging in the differential diagnosis of glioma recurrence and radiation brain injury

    Directory of Open Access Journals (Sweden)

    Guang-zhi GE

    2015-11-01

    Full Text Available Objective  To explore the application of a combination of diFFusion weighted imaging (DWI, perfusion weighted imaging (PWI and magnetic resonance spectroscopy (MRS in the differential diagnosis of glioma recurrence and radiation brain injury. Methods The clinical and imaging data of 32 patients were retrospectively analyzed, including 15 cases of glioma recurrence and 17 cases of radiation brain injury, admitted from Jan. 2011 to Dec. 2013 in General Hospital of Beijing Command. The DWI, PWI and MRS data of the 32 patients were retrospectively analyzed. The following values were compared between abnormal enhancement area and contralateral normal area: magnetic resonance apparent diFFusion coeFFcient (ADC, relative cerebral blood flow (rCBF, relative cerebral blood volume (rCBV, relative mean transit time (rMTT, choline/creatine (Cho/Cr and choline/N-acetyl aspartate (Cho/ NAA ratio. Results No statistical significance of ADC and rMTT values was found between glioma recurrence group and radiation brain injury group (P>0.05; The maximum and average rCBF and rCBV values were significantly higher in glioma recurrence group than in radiation brain injury group (P0.05. The ratios of Cho/Cr and Cho/NAA were higher in glioma recurrence group than in radiation brain injury group (P<0.05. The diagnostic sensitivity of PWI to glioma recurrence was 80.0%, of MRS was 73.3%, and of PWI combined with MRS was 93.3%. The diagnostic sensitivity of PWI to radiation brain injury was 82.4%, of MRS was 70.6%, and of PWI combined with MRS was 88.2%. Conclusion Combined application of multimodal magnetic resonance imaging technology may improve the diagnostic accuracy to glioma recurrence and radiation brain injury, thus provide a good guidance for clinical treatment. DOI: 10.11855/j.issn.0577-7402.2015.11.13

  14. The effect of pentoxifylline on early and late radiation injury following fractionated irradiation in C3H mice

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    Dion, M.W.; Hussey, D.H.; Osborne, J.W.

    1989-07-01

    An experiment was performed to test the effectiveness of pentoxifylline in reducing late radiation injury. One hundred and four C3H mice were randomized into eight groups of 13 mice each, and the right hind limbs were irradiated with 4000, 5000, 6000, or 7000 cGy in ten fractions. Each group was treated with once daily injections of either pentoxifylline or saline for 30+ weeks. An additional ten mice received daily injections of pentoxifylline or saline, but no irradiation. The pentoxifylline animals demonstrated significantly less late injury than the saline treated animals. The most obvious differences were observed in the 5000 and 6000 cGy groups. There were seven radiation related deaths in the saline treated control groups, but only one radiation related death in the pentoxifylline treated groups. Whereas 42% (20/48) of the saline treated animals had a late injury score of 3.0 or greater, only 8% (4/51) of the pentoxifylline treated animals had a late skin score as high as 3.0. Pentoxifylline had no effect on the acute radiation injury scores. The drug was well tolerated with no toxic effects noted. Pentoxifylline is a methyl xanthine derivative that is used to treat vascular occlusive disease in humans. It improves perfusion through small capillaries by improving the deformability of red blood cells, inhibiting platelet aggregation, and stimulating the release of prostacyclin. This study shows that the prophylactic administration of pentoxifylline can modify late radiation induced injury in the mouse extremity. It may have value in the prevention or treatment of late radiation induced injury in humans, and it could be a useful tool to help define the mechanisms of late radiation injury in specific organs.

  15. The Long Term Effects of Chronic Spinal Cord Injury on Sperm Parameters in Rats

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    MA Khalili

    2004-07-01

    Full Text Available Introduction: Spinal cord injury (SCI is a serious public health problem which seriously affects the victim, family, and even the society. Research studies have shown that 80% of SCI victims are men. In recent years, there have been extensive research works on the effect of SCI (acute and/or chronic on fertility potential of sperm and spermatogenesis in laboratory animals. SCI may disturb the spermatogenic cell lines in laboratory animals. The objective of this experimental study was to investigate the effect of chronic spinal cord injury (CSCI on sperm parameters in adult rats. Materials & Methods: Adult Wistar rats weighing between 225-275g were divided into 3groups of control (n=5, sham (n=10, and experimental CSCI (n=10. No surgery was done on control animals. Only laminectomy was done in the sham animals at T10. CSCI was developed in experimental rats using 10g weight dropped 5cm above the exposed T10 level. All animals were sacrificed 50 days post experiment to extract epididymal samples. Sperm parameters of count, motility, morphology, as well as number of round cells were evaluated with the aid of Makler chamber and Geimsa staining. Results: Progressive motility was significantly reduced in CSCI group (P<0.05. The percentage of normal morphology of spermatozoa was 99.0±1.0 in control rats which was significantly reduced to 74.90±37.64 in CSCI animals In addition, sperm counts in control and CSCI rats were 69.20±12.43 and 25.0±13.68, respectively (P<0.01. Round cell concentration was increased in CSCI group as compared to controls. Conclusion: The results suggest that reduction in parameters of progressive motility, morphology, as well as sperm count following CSCI in rats may disturb the fertility potential of spermatozoa.

  16. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

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    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

    2016-10-01

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  17. Reaction of fresh water zooplankton community to chronic radiation exposure

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    Osipov, D.; Pryakhin, E. [Urals Research Center for Radiation Medicine - URCRM (Russian Federation); Ivanov, I. [FSUE Mayak PA (Russian Federation)

    2014-07-01

    The characteristic features of ecological community as a whole and cenosis of zooplankton organisms as part of it determine the intensity of the processes of self-purification of water and the formation of a particular body of water. Identifying features of the structure and composition of the zooplankton community of aquatic ecosystems exposed to different levels of radiation exposure, it is necessary to identify patterns of changes in zooplankton and hydro-biocenosis as a whole. Industrial reservoirs, the storage of liquid low-level radioactive waste 'Mayak' for decades, have high radiation load. A large range of levels of radioactive contamination (total volume beta-activity in water varies from 2.2x10{sup 3} to 2.3x10{sup 7} Bq/l, total volume alpha-activity - from 2.6x10{sup -1} to 3.1x10{sup 3} Bq/l) provides a unique opportunity to study ecosystems in a number of reservoirs with increasing impact of radiation factor. We studied five reservoirs that were used as the storage of low-and intermediate-level liquid radioactive waste pond and one comparison water body. In parallel with zooplankton sampling water samples were collected for hydro-chemical analysis. 41 indicators were analysed in order to assess the water chemistry. To determine the content of radionuclides in the various components of the ecosystem samples were collected from water, bottom sediments and plankton. Sampling of zooplankton for the quantitative analysis was performed using the method of weighted average auto bathometer. Apshteyn's plankton net of the surface horizon was used for qualitative analysis of the species composition of zooplankton. Software package ERICA Assessment Tool 2012 was used for the calculation of the absorbed dose rate. Species diversity and biomass of zooplankton, the share of rotifers in the number of species, abundance and biomass decrease with the increase of the absorbed dose rate and salinity. The number of species in a sample decreases with the

  18. Analysis of chronic radiation exposure at small doses

    Energy Technology Data Exchange (ETDEWEB)

    Krestinina, L.Y. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)

    2000-05-01

    The purpose of the study was to analyze the late effects of radiation exposure among residents of settlements located on the territory of the East-Urals Radiation Trace (EURT) in the Southern Urals. In 1957 an explosion occurred at the depot of radioactive waste in the Southern Urals. An area of 23000 km{sup 2} was contaminated, with contamination density of over 0.1 Ci/m{sup 2} for {sup 90}Sr. There were 217 populated ares on that territory with total population about 270000. The residents of 22 villages with contamination density of over 4 Ci/km{sup 2} for {sup 90}Sr were evacuated. The times of evacuation differed from 7 to 670 days since the accident, depending on the level of contamination. In 1988-1993 an individualized registry was created at the Urals Research Center for Radiation Medicine (URCRM) which included information on the residents of 22 evacuated villages and a proportion of unevacuated residents of the EURT area. Currently, the registry contains data on 30000 residents. Of that number 17000 persons were born before, and 12000 after the accident (including about 9000 offspring of exposed residents evacuated from the EURT, and about 3000 persons who were born after the accident and have been living permanently in the EURT area). Over the 35-year period since the accident the residents have received mean effective doses ranging from 23 to 530 mSv. The mean effective doses received by permanent residents range from 5 to 60 mSv. The cohort of people exposed on the EURT territory was identified based on the information contained in the registry. If a person happened to be in the EURT area at the time of the accident, he/she was considered to be eligible for inclusion in the cohort. Over the 35-year period (from 1957 through 1992) 29.5% of 17872 residents died, and 35% of the original cohort were lost to follow-up for different reasons. To enable an analysis a control group was established which included residents of villages located outside, but close

  19. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

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    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  20. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Puchelle, Edith; Zahm, Jean-Marie; Tournier, Jean-Marie; Coraux, Christelle

    2006-11-01

    In chronic obstructive pulmonary disease (COPD), exacerbations are generally associated with several causes, including pollutants, viruses, bacteria that are responsible for an excess of inflammatory mediators, and proinflammatory cytokines released by activated epithelial and inflammatory cells. The normal response of the airway surface epithelium to injury includes a succession of cellular events, varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even complete denudation of the basement membrane. The epithelium then has to repair and regenerate to restore its functions, through several mechanisms, including basal cell spreading and migration, followed by proliferation and differentiation of epithelial cells. In COPD, the remodeling of the airway epithelium, such as squamous metaplasia and mucous hyperplasia that occur during injury, may considerably disturb the innate immune functions of the airway epithelium. In vitro and in vivo models of airway epithelial wound repair and regeneration allow the study of the spatiotemporal modulation of cellular and molecular interaction factors-namely, the proinflammatory cytokines, the matrix metalloproteinases and their inhibitors, and the intercellular adhesion molecules. These factors may be markedly altered during exacerbation periods of COPD and their dysregulation may induce remodeling of the airway mucosa and a leakiness of the airway surface epithelium. More knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to cytoprotective and regenerative therapeutics, allowing the reconstitution of a functional, well-differentiated airway epithelium in COPD.

  1. Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

    Science.gov (United States)

    Cheng, Shun-Yang; Chou, Yu-Hsiang; Liao, Fang-Ling; Lin, Chi-Chun; Chang, Fan-Chi; Liu, Chia-Hao; Huang, Tao-Min; Lai, Chun-Fu; Lin, Yu-Feng; Wu, Vin-Cent; Chu, Tzong-Shinn; Wu, Ming-Shiou; Lin, Shuei-Liong

    2016-01-01

    Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI. PMID:27677327

  2. The effect of oxidative stress in myocardial cell injury in mice exposed to chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-nan; ZHANG Jie-xin; LIU gan; QIU Yan; YANG Di; YIN Guo-yong; ZHANG Xi-long

    2010-01-01

    Background Obstructive sleep apnea syndrome (OSAS) is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine (NAC). Methods Thirty ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH+NAC) groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I (cTnl) was detected by enzyme-linked immunosorbent assays (ELISA). Myocardium pathological sections were observed.Results (1) The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups (P <0.005). The MDA concentration of the NAC group was lower than that of the control group (P <0.01). (2) The serum cTnl concentration of the CIH and NAC groups was significantly higher than that of the control group (P<0.01). (3) Serum triglyceride levels in the NAC group were lower than in the other groups (P<0.01), while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. (4) The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group.Conclusion The oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.

  3. Transcranial LED therapy for cognitive dysfunction in chronic, mild traumatic brain injury: two case reports

    Science.gov (United States)

    Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2010-02-01

    Two chronic, traumatic brain injury (TBI) cases are presented, where cognitive function improved following treatment with transcranial light emitting diodes (LEDs). At age 59, P1 had closed-head injury from a motor vehicle accident (MVA) without loss of consciousness and normal MRI, but unable to return to work as development specialist in internet marketing, due to cognitive dysfunction. At 7 years post-MVA, she began transcranial LED treatments with cluster heads (2.1" diameter with 61 diodes each - 9x633nm, 52x870nm; 12-15mW per diode; total power, 500mW; 22.2 mW/cm2) on bilateral frontal, temporal, parietal, occipital and midline sagittal areas (13.3 J/cm2 at scalp, estimated 0.4 J/cm2 to brain cortex per area). Prior to transcranial LED, focused time on computer was 20 minutes. After 2 months of weekly, transcranial LED treatments, increased to 3 hours on computer. Performs nightly home treatments (now, 5 years, age 72); if stops treating >2 weeks, regresses. P2 (age 52F) had history of closed-head injuries related to sports/military training and recent fall. MRI shows fronto-parietal cortical atrophy. Pre-LED, was not able to work for 6 months and scored below average on attention, memory and executive function. Performed nightly transcranial LED treatments at home (9 months) with similar LED device, on frontal and parietal areas. After 4 months of LED treatments, returned to work as executive consultant, international technology consulting firm. Neuropsychological testing (post- 9 months of transcranial LED) showed significant improvement in memory and executive functioning (range, +1 to +2 SD improvement). Case 2 reported reduction in PTSD symptoms.

  4. Diethylcarbamazine Reduces Chronic Inflammation and Fibrosis in Carbon Tetrachloride- (CCl4- Induced Liver Injury in Mice

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    Sura Wanessa Santos Rocha

    2014-01-01

    Full Text Available This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl4 0.5 μL/g of body weight through two injections a week for 6 weeks. DEC (50 mg/kg was administered by gavage for 12 days before finishing the CCl4 induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1β, MDA, TGF-β, and αSMA immunopositivity, besides exhibiting decreased IL1β, COX-2, NFκB, IFNγ, and TGFβ expressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.

  5. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome.

    Science.gov (United States)

    Chawla, Lakhmir S; Kimmel, Paul L

    2012-09-01

    The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.

  6. Chemical modification of radiation injury in granuloid cells of mouse bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Bhagat, R.M.; Kumar, A. (Himachal Pradesh Univ., Simla (India). Dept. of Bio-sciences)

    1983-08-01

    Modifying effects of MPG (2-Mercaptopropionylglycine) have been studied on bone marrow granuloid cells of Swiss albino mice after injecting radiocalcium (/sup 45/Ca) at the dose of 37 kBq/g body weight MPG was injected 30 minutes before radiocalcium injection at dose 20 mg/kg body weight intraperitoneally and also MPG was injected at various repeated doses. Present observations indicate that MPG in repeated doses is effective in reducing radiation injury in bone marrow granuloid cells of Swiss albino mice following radiocalcium (/sup 45/Ca) internal irradiation.

  7. Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mithun Diwakar

    2015-01-01

    Full Text Available A barrier in the diagnosis of mild traumatic brain injury (mTBI stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS, and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG, which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition. MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and

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

    Energy Technology Data Exchange (ETDEWEB)

    Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C., E-mail: prabhat-goswami@uiowa.edu

    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.

  9. A case of chronic progressive radiation myelopathy treated with long-time corticosteroid administration

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Saeko; Soejima, Toshinori; Higashino, Takanori; Obayashi, Kayoko; Takada, Yoshiki [Hyogo Medical Center for Adults, Akashi (Japan); Hishikawa, Yoshio

    1998-05-01

    This is a report of one patient who developed chronic progressive radiation myelopathy at a gap of two portals 31 months after 40 Gy irradiation. He presented an unusual clinical course with over 5 years and 6 months administration of oral corticosteroid, very slow progression and long-lasting presentation of Gd-DTPA enhanced area in the suffered cord by MRI. It is suggested that corticosteroid administration from initial onset for a long period may change the natural course of radiation myelopathy, that is, may delay progress of it. (author)

  10. Cognitive Gains from Gist Reasoning Training in Adolescents with Chronic-Stage Traumatic Brain Injury

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    Lori G. Cook

    2014-06-01

    Full Text Available Adolescents with traumatic brain injury (TBI typically demonstrate good recovery of previously acquired skills. However, higher-order and later emergent cognitive functions are often impaired and linked to poor outcomes in academic and social/behavioral domains. Few control trials exist that test cognitive treatment effectiveness at chronic recovery stages. The current pilot study compared the effects of two forms of cognitive training, gist reasoning (top-down versus rote memory learning (bottom-up, on ability to abstract meanings, recall facts, and utilize core executive functions (i.e., working memory, inhibition in 20 adolescents (ages 12-20 who were six months or longer post-TBI. Participants completed eight 45-minute sessions over one month. After training, the gist reasoning group (n = 10 exhibited significant improvement in ability to abstract meanings and increased fact recall. This group also showed significant generalizations to untrained executive functions of working memory and inhibition. The memory training group (n = 10 failed to show significant gains in ability to abstract meaning or on other untrained specialized executive functions, although improved fact recall approached significance. These preliminary results suggest that relatively short-term training (6 hours utilizing a top-down reasoning approach is more effective than a bottom-up rote learning approach in achieving gains in higher-order cognitive abilities in adolescents at chronic stages of TBI. These findings need to be replicated in a larger study; nonetheless, the preliminary data suggest that traditional cognitive intervention schedules need to extend to later-stage training opportunities. Chronic-stage, higher-order cognitive trainings may serve to elevate levels of cognitive performance in adolescents with TBI.

  11. High-Throughput Proteomic Approaches to the Elucidation of Potential Biomarkers of Chronic Allograft Injury (CAI

    Directory of Open Access Journals (Sweden)

    Hilary Cassidy

    2013-09-01

    Full Text Available This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI. CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG. The term CAI, sometimes referred to as chronic allograft nephropathy (CAN, describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection, and other non-immunological factors such as calcineurin inhibitor (CNI induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kageji, T. E-mail: kageji@clin.med.tokushima-u.ac.jp; 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

  13. Effect of WeiJia on carbon tetrachloride induced chronic liver injury

    Institute of Scientific and Technical Information of China (English)

    Pik-Yuen Cheung; Jay Chun; Hsiang-Fu Kung; Meng-su Yang; Qi Zhang; Ya-Ou Zhang; Gan-Rong Bai; Marie Chia-Mi Lin; Bernard Chan; Chi-Chun Fong; Lin Shi; Yue-Feng Shi

    2006-01-01

    AIM: To study the effect of WeiJia on chronic liver injury using carbon tetrachloride (CCl4) induced liver injury animal model.METHODS: Wistar rats weighing 180-220g were randomly divided into three groups: normal control group (Group A), CCl4 induced liver injury control group (Group B) and CCl4 induction with WeiJia treatment group (Group C). Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCl4 in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week,Group C rats also received daily intraperitoneal injection of WeiJia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week (4 male, 3 female), and eighth week (4 male, 3 female) respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid (HA), type Ⅳ collagen (CIV), γ-glutamyl transferase (γ-GT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) immunohistochemistry were also performed.RESULTS: CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and Y-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L (P0.05) respectively, similar to normal control group (Group A), but significantly different from CCl4 induced liver injury control group (Group B). An increase in PCNA and decrease in a-SMA expression level was also observed.CONCLUSION: WeiJia could improve liver function and reduce liver fibrosis

  14. Neurotrophic factor changes in the rat thick skin following chronic constriction injury of the sciatic nerve

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    Peleshok Jennifer C

    2012-01-01

    Full Text Available Abstract Background Cutaneous peripheral neuropathies have been associated with changes of the sensory fiber innervation in the dermis and epidermis. These changes are mediated in part by the increase in local expression of trophic factors. Increase in target tissue nerve growth factor has been implicated in the promotion of peptidergic afferent and sympathetic efferent sprouting following nerve injury. The primary source of nerve growth factor is cells found in the target tissue, namely the skin. Recent evidence regarding the release and extracellular maturation of nerve growth factor indicate that it is produced in its precursor form and matured in the extracellular space. It is our hypothesis that the precursor form of nerve growth factor should be detectable in those cell types producing it. To date, limitations in available immunohistochemical tools have restricted efforts in obtaining an accurate distribution of nerve growth factor in the skin of naïve animals and those with neuropathic pain lesions. It is the objective of this study to delineate the distribution of the precursor form of nerve growth factor to those cell types expressing it, as well as to describe its distribution with respect to those nerve fibers responsive to it. Results We observed a decrease in peptidergic fiber innervation at 1 week after the application of a chronic constriction injury (CCI to the sciatic nerve, followed by a recovery, correlating with TrkA protein levels. ProNGF expression in CCI animals was significantly higher than in sham-operated controls from 1-4 weeks post-CCI. ProNGF immunoreactivity was increased in mast cells at 1 week post-CCI and, at later time points, in keratinocytes. P75 expression within the dermis and epidermis was significantly higher in CCI-operated animals than in controls and these changes were localized to neuronal and non-neuronal cell populations using specific markers for each. Conclusions We describe proNGF expression by

  15. Analysis of Chronic Radiation Sickness Cases in the Population of the Southern Urals

    Science.gov (United States)

    1994-08-01

    radiation were conducted as part of this study, which is a detailed retrospective review of the effects of exposures resulting from either accidental or...chronic coronary number of segmented neutrophils. The number of insufficiency and cerebrovascular sclerosis in 1972; reticular cells, plasmatic cells...osteomuscular system 4 Heart diseases of pulmonary origin 25 Osteomyelitis 4 Ischemic heart disease 10 Cerebrovascular diseases 12 Trauma 22

  16. In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses.

    Science.gov (United States)

    Shukla, Shivendra D; Aroor, Annayya R; Restrepo, Ricardo; Kharbanda, Kusum K; Ibdah, Jamal A

    2015-11-20

    Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

  17. Protective effect of vitamin A on acute radiation injury in the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Beyzadeoglu, Murat; Balkan, Mujdat; Demiriz, Murat; Dirican, Bahar; Oner, Koksal; Pak, Yucel [Gulhane Military Medical Academy, Ankara (Turkey); Tibet, Hasan

    1997-01-01

    The objective of this study was to examine the influence of vitamin A on the development of early radiation-induced reactions in the rat small intestine. The early effects of intraoperative gamma-radiation on the small bowel utilizing the terminal ileum of Sprague-Dawley rats and the protective effect of supplemental vitamin A on acute radiation injury were investigated. Three groups were included in the study: group I (10 rats) was the surgical control group; group II (13 rats) underwent only intraoperative irradiation; and group III (10 rats) was the vitamin A plus irradiation group. Exteriorized terminal ileal segments of groups II and III were exposed to a single fraction of 20 Gy of intraoperative gamma-irradiation. On the seventh postoperative day, terminal ileal segments of all rats were resected and histopathologically evaluated for ulceration, enteritis cystica profunda, atypical epithelial regeneration, fibrosis, vascular sclerosis, and inflammatory process. Although none of the above findings were present in the surgical control group, group III rats experienced less severe effects than group II rats. The results suggest the early side effects of radiation may be prevented by vitamin A supplementation. (author)

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

    Directory of Open Access Journals (Sweden)

    Hua Wang

    Full Text Available 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.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.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.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.

  19. Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

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    Keirstead Hans S

    2007-09-01

    Full Text Available Abstract Background Chronic spinal cord injury (SCI can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Methods Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4, 28 (n = 4, 120 (n = 4, 450 (n = 5, or 540 (n = 5 days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures. Results Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil. Conclusion Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of

  20. Activation of chemical biological defense mechanisms and remission of vital oxidative injury by low dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yamaoka, K. [Okayama University Medical School, Okayama (Japan); Nomura, T. [Central Research Institute of Electric Power Industry, Tokyo (Japan); Kojima, S. [Science University of Tokyo, Chiba (Japan)

    2000-05-01

    Excessive active oxygen produced in vivo by various causes is toxic. Accumulation of oxidation injuries due to excessive active causes cell and tissue injuries, inducing various pathologic conditions such as aging and carcinogenesis. On the other hand, there are chemical defense mechanisms in the body that eliminate active oxygen or repair damaged molecules, defending against resultant injury. It is interesting reports that appropriate oxidation stress activate the chemical biological defense mechanisms. In this study, to elucidate these phenomena and its mechanism by low dose radiation, we studied on the below subjects. Activation of chemical biological defense mechanisms by low dose radiation: (1) The effects radiation on lipid peroxide (LPO) levels in the organs, membrane fluidity and the superoxide dismutase (SOD) activity were examined in rats and rabbits. Rats were irradiated with low dose X-ray over their entire bodies, and rabbits inhaled vaporized radon spring water, which primarily emitted {alpha}-ray. The following results were obtained. Unlike high dose X-ray, low dose X-ray and radon inhalation both reduced LPO levels and made the state of the SH-group on membrane-bound proteins closer to that of juvenile animals, although the sensitivity to radioactivity varied depending on the age of the animals and among different organs and tissues. The SOD activity was elevated, suggesting that low dose X-ray and radon both activate the host defensive function. Those changes were particularly marked in the organs related to immune functions of the animals which received low dose X-ray, while they were particularly marked in the brain after radon inhalation. It was also found that those changes continued for longer periods after low dose X-irradiation. (2) Since SOD is an enzyme that mediates the dismutation of O{sub 2}- to H{sub 2}O{sub 2}, the question as to whether the resultant H{sub 2}O{sub 2} is further detoxicated into H{sub 2}O and O{sub 2} or not must

  1. Clinical value of renal injury biomarkers in diagnosis of chronic kidney disease

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    Cheng-lu ZHANG

    2011-12-01

    Full Text Available Objective To investigate the levels of renal injury biomarkers in patients with chronic kidney disease(CKD and evaluate their clinical significances in diagnosis of CKD.Methods A total of 66 subjects(37 patients with CKD and 29 healthy individuals were involved in this study.Serum blood urea nitrogen(SBUN was determined by Glutamate dehydrogenase method;serum creatinine(SCr and urinary creatinine(UCr were detected by sarcosine oxidase method;serum uric acid(SUA was measured by uricase colorimetry;serum cystatin C(Cys C and urinary microalbumin(UmAlbwere analyzed by immunological transmission turbidimetry;urinary protein(U-PROwas measured by Coomassies Brilliant Blue(CBB assay.The UmAlb and U-PRO levels were expressed in units of mg/mmolUCr.Results The results of independent samples t test indicated that significant differences were found in SBUN,SCr,SUA,Cys C,UmAlb and U-PRO(P < 0.05 between patient group and healthy control group.The evaluation of diagnostic effects showed that the areas under the curve at ROC plot for SBUN,SCr,SUA,Cys C,UmAlb and U-PRO were 0.907,0.912,0.742,0.982,0.984 and 0.991,respectively.Conclusions U-PRO,UmAlb and Cys C are ideal biomarkers,SCr and SBUN come next,SUA is the weakest when the above biomarkers are applied to evaluate the renal injury and its severity of the patients with CKD.

  2. Chronic bilateral renal denervation attenuates renal injury in a transgenic rat model of diabetic nephropathy.

    Science.gov (United States)

    Yao, Yimin; Fomison-Nurse, Ingrid C; Harrison, Joanne C; Walker, Robert J; Davis, Gerard; Sammut, Ivan A

    2014-08-01

    Bilateral renal denervation (BRD) has been shown to reduce hypertension and improve renal function in both human and experimental studies. We hypothesized that chronic intervention with BRD may also attenuate renal injury and fibrosis in diabetic nephropathy. This hypothesis was examined in a female streptozotocin-induced diabetic (mRen-2)27 rat (TGR) shown to capture the cardinal features of human diabetic nephropathy. Following diabetic induction, BRD/sham surgeries were conducted repeatedly (at the week 3, 6, and 9 following induction) in both diabetic and normoglycemic animals. Renal denervation resulted in a progressive decrease in systolic blood pressure from first denervation to termination (at 12 wk post-diabetic induction) in both normoglycemic and diabetic rats. Renal norepinephrine content was significantly raised following diabetic induction and ablated in denervated normoglycemic and diabetic groups. A significant increase in glomerular basement membrane thickening and mesangial expansion was seen in the diabetic kidneys; this morphological appearance was markedly reduced by BRD. Immunohistochemistry and protein densitometric analysis of diabetic innervated kidneys confirmed the presence of significantly increased levels of collagens I and IV, α-smooth muscle actin, the ANG II type 1 receptor, and transforming growth factor-β. Renal denervation significantly reduced protein expression of these fibrotic markers. Furthermore, BRD attenuated albuminuria and prevented the loss of glomerular podocin expression in these diabetic animals. In conclusion, BRD decreases systolic blood pressure and reduces the development of renal fibrosis, glomerulosclerosis, and albuminuria in this model of diabetic nephropathy. The evidence presented strongly suggests that renal denervation may serve as a therapeutic intervention to attenuate the progression of renal injury in diabetic nephropathy.

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

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    Yabin Duan

    2015-07-01

    Full Text Available 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.

  4. Practical approaches to effective management of intestinal radiation injury: Benefit of resectional surgery

    Institute of Scientific and Technical Information of China (English)

    Nikolaos Perrakis; Evangelos Athanassiou; Dimitra Vamvakopoulou; Maria Kyriazi; Haris Kappos; Nikolaos C Vamvakopoulos; Iakovos Nomikos

    2011-01-01

    AIM: To study the outcome of patients undergoing surgical resection of the bowel for sustained radiation-induced damage intractable to conservative management.METHODS: During a 7-year period we operated on 17 cases (5 male, 12 female) admitted to our surgical department with intestinal radiation injury (IRI). They were originally treated for a pelvic malignancy by surgical resection followed by postoperative radiotherapy. During follow-up, they developed radiation enteritis requiring surgical treatment due to failure of conservative management.RESULTS: IRI was located in the terminal ileum in 12 patients, in the rectum in 2 patients, in the descending colon in 2 patients, and in the cecum in one patient. All patients had resection of the affected region(s). There were no postoperative deaths, while 3 cases presented with postoperative complications (17.7%). All patients remained free of symptoms without evidence of recurrence of IRI for a median follow-up period of 42 mo (range, 6-96 mo).CONCLUSION: We report a favorable outcome without IRI recurrence of 17 patients treated by resection of the diseased bowel segment.

  5. The role of alveolar epithelium in radiation-induced lung injury.

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    Celine Almeida

    Full Text Available 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.

  6. Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats.

    Science.gov (United States)

    Chu, JianJun; Zhang, Xiaojun; Jin, Liugen; Chen, Junliang; Du, Bin; Pang, Qingfeng

    2015-03-01

    Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague-Dawley rats were intraperitoneally administered with CAPE (30 mg/kg) for 3 consecutive days before exposing them to a single dose of 30 Gy of β-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-κB p65 subunit, decreased the level of tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury.

  7. The role of alveolar epithelium in radiation-induced lung injury.

    Science.gov (United States)

    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 (137)Cs 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Effects of six weeks of chronic ethanol administration on the behavioral outcome of rats after lateral fluid percussion brain injury.

    Science.gov (United States)

    Zhang, L; Maki, A; Dhillon, H S; Barron, S; Clerici, W J; Hicks, R; Kraemer, P J; Butcher, J; Prasad, R M

    1999-03-01

    This study examined the effects of 6 weeks of chronic ethanol administration on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet-groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 6 weeks. After 6 weeks, the ethanol diet was discontinued for the ethanol diet rats and they were then given the control sucrose diet for 2 days. During those 2 days, the rats were trained to perform a beam-walking task and subjected to either lateral FP brain injury of low to moderate severity (1.8 atm) or to sham operation. In both the control diet and the ethanol diet groups, lateral FP brain injury caused beam-walking impairment on days 1 and 2 and spatial learning disability on days 7 and 8 after brain injury. There were no significant differences in beam-walking performance and spatial learning disability between brain injured animals from the control and ethanol diet groups. However, a trend towards greater behavioral deficits was observed in brain injured animals in the ethanol diet group. Histologic analysis of both diet groups after behavioral assessment revealed comparable ipsilateral cortical damage and observable CA3 neuronal loss in the ipsilateral hippocampus. These results only suggest that chronic ethanol administration, longer than six weeks of administration, may worsen behavioral outcome following lateral FP brain injury. For more significant behavioral and/or morphological change to occur, we would suggest that the duration of chronic ethanol administration must be increased.

  11. Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury PCS and PTSD

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-10-1-0962 TITLE: Hyperbaric Oxygen therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury...Annual 3. DATES COVERED (From – To) 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0962 Hyperbaric Oxygen therapy in...post- hyperbaric oxygen treatment. Four additional subjects have been screened in October 2015 and nine are awaiting first appointment for

  12. Reflex responses to combined hip and knee motion in human chronic spinal cord injury

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    Ming Wu, PhD

    2010-04-01

    Full Text Available The relative contributions of hip and knee proprioceptors to the origination of extensor spasms were examined in 11 subjects with chronic spinal cord injury (SCI. Ramp and hold extension and combined hip and knee oscillation movements were imposed to the right leg while the ankle was held in a static position by a custom-designed robot. Isometric joint torques of the hip, knee, and ankle and surface electromyograms (EMGs from seven leg muscles were recorded following controlled hip and knee extension. A stereotypical torque response consisting of hip flexion, knee extension, and ankle plantar flexion was observed following hip and knee perturbations. Further, the hip or knee joint posture modulated the spastic reflexes triggered by the extension movement of the other joint, with larger responses observed with the hip and knee extended. In addition, combined hip and knee oscillation movements were imposed to one leg with four different phasing conditions. The phasing between the hip and knee modulated the reflex activity triggered by hip and knee oscillations. The EMG patterns of the spastic reflexes were generally consistent with muscle timing during locomotion in human SCI. This knowledge may help identify rehabilitation strategies that produce functional movements in human SCI.

  13. Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis

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    Nikolaos P. Karidis

    2015-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV- related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

  14. Acupuncture for Chronic Urinary Retention due to Spinal Cord Injury: A Systematic Review

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    Jia Wang

    2016-01-01

    Full Text Available No systematic review has been published on the use of acupuncture for the treatment of chronic urinary retention (CUR due to spinal cord injury (SCI. The aim of this review was to assess the effectiveness and safety of acupuncture for CUR due to SCI. Three randomized controlled trials (RCTs including 334 patients with CUR due to SCI were included. Meta-analysis showed that acupuncture plus rehabilitation training was much better than rehabilitation training alone in decreasing postvoid residual (PVR urine volume (MD −109.44, 95% CI −156.53 to −62.35. Likewise, a combination of acupuncture and aseptic intermittent catheterization was better than aseptic intermittent catheterization alone in improving response rates (RR 1.23, 95% CI 1.10 to 1.38. No severe adverse events were reported. In conclusion, acupuncture as a complementary therapy may have a potential effect in CUR due to SCI in decreasing PVR and improving bladder voiding. Additionally, acupuncture may be safe in treating CUR caused by SCI. However, due to the lack of high quality RCTs, we could not draw any definitive conclusions. More well-designed RCTs are needed to provide strong evidence.

  15. Managing severe burn injuries: challenges and solutions in complex and chronic wound care

    Directory of Open Access Journals (Sweden)

    Rogers AD

    2016-06-01

    Full Text Available Alan D Rogers, Marc G Jeschke Ross Tilley Burn Centre, Division of Plastic and Reconstructive Surgery, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada Abstract: Encountered regularly by health care providers across both medical and surgical fields and an increasing socioeconomic burden globally, wound care is severely neglected. Practice is heavily influenced by anecdote rather than evidence-based protocols and industry-biased literature rather than robust randomized controlled trials. Burn units are well placed to address this considerable need, as a result of their infrastructure, their multispecialty staffing, and their need to evolve in light of the declining incidence of major burn injury in developed countries. The aim of this review is to evaluate some of the ideological and practical challenges facing wound practitioners and burn surgeons while managing chronic and complex wounds. It also includes an approach to wound assessment and how to conceptualize and implement dressing strategies and new and existing multimodal therapies. Keywords: negative pressure wound therapy, instillation, antiseptic solutions, dressings, multidisciplinary wound care, stem cells, surgery, autograft, allograft, reconstructive ladder

  16. Analgesic effect of gabapentin in a rat model for chronic constrictive injury

    Institute of Scientific and Technical Information of China (English)

    MA Lu-lu; LIU Wei; HUANG Yu-guang; YANG Nan; ZUO Ping-ping

    2011-01-01

    Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade,however its analgesic mechanisms are still elusive.Our study was to investigate whether Ca2+/calmodulin-dependent protein kinase II (CaMKII) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model.Methods Gabapentin (2%,100 mg/kg) or saline (0.5 mil100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control,sham and CCI groups.The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats.Expression and activation of CaMKII were quantified by reverse-transcriptional polymerase chain reaction and Western blotting.Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model,with maximal reduction reached on postoperative day 8.Gabapentin decreased the expression of the total CaMKII and phosphorylated CaMKII in CCI rats.Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKII in the spinal cord.

  17. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  18. Serum γ-glutamyltransferase activity as an indicator of chronic liver injury in cattle with no clinical signs

    Directory of Open Access Journals (Sweden)

    C.N. Moreira

    2012-12-01

    Full Text Available This study aimed to determine the power of the serum aspartate aminotransferase (AST and gamma-glutamyltransferasase (GGT activities and of the albumin and cholesterol dosages for detecting hepatic histopathological injuries. A total of 220 healthy male Nelore cattle that had been extensively bred were evaluated. Blood and liver samples were collected on the day of slaughter for biochemical and histopathological tests. The results showed that the sensitivity to AST, GGT, albumin, and cholesterol tests were respectively 22.4%, 22.4%, 36%, and 37.2%. The specificity of AST, GGT, albumin, and cholesterol tests was respectively 78.8%, 90.4%, 75.6%, and 68.3%. In short, the detection of minor liver injuries through biochemical tests is limited; however, the high specificity of the GGT allows its use as an indicator of hepatic chronic injuries in cattle herds.

  19. Long-Term Use and Perceived Benefits of Goal-Oriented Attentional Self-Regulation Training in Chronic Brain Injury

    Science.gov (United States)

    Novakovic-Agopian, Tatjana; Binder, Deborah; Rossi, Annemarie; Rome, Scott; Murphy, Michelle; Chen, Anthony J.-W.

    2017-01-01

    Primary Objective. To investigate the long-term use and perceived benefit(s) of strategies included in Goal-Oriented Attentional Self-Regulation (GOALS) training (Novakovic-Agopian et al., 2011) by individuals with acquired brain injury (ABI) and chronic executive dysfunction. Research Design. Longitudinal follow-up of training. Methods and Procedures. Sixteen participants with chronic ABI participated in structured telephone interviews 20 months (range 11 to 31 months) following completion of GOALS training. Participants responded to questions regarding the range of strategies they continued to utilize, perceived benefit(s) of strategy use, situations in which strategy use was found helpful, and functional changes attributed to training. Results. Nearly all participants (94%) reported continued use of at least one trained strategy in their daily lives, with 75% of participants also reporting improved functioning resulting from training. However, there was considerable variability with respect to the specific strategies individuals found helpful as well as the perceived impact of training on overall functioning. Conclusions. GOALS training shows promising long-term benefits for individuals in the chronic phase of brain injury. Identifying individual- and injury-level factors that account for variability in continued strategy use and the perceived long-term benefits of training will help with ongoing intervention development.

  20. Late infusion of cloned marrow fibroblasts stimulates endogenous recovery from radiation-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Mineo Iwata

    Full Text Available In the current study, we used a canine model of radiation-induced lung injury to test the effect of a single i.v. infusion of 10×10(6/kg of marrow fibroblasts on the progression of damage following 15 Gy exposure to the right lung. The fibroblasts, designated DS1 cells, are a cloned population of immortalized cells isolated from a primary culture of marrow stromal cells. DS1 cells were infused at week 5 post-irradiation when lung damage was evident by imaging with high-resolution computed tomography (CT. At 13 weeks post-irradiation we found that 4 out of 5 dogs receiving DS1 cells had significantly improved pulmonary function compared to 0 out of 5 control dogs (p = 0.047, Fisher's Exact. Pulmonary function was measured as the single breath diffusion capacity-hematocrit (DLCO-Hct, the total inspiratory capacity (IC, and the total lung capacity (TLC, which differed significantly between control and DS1-treated dogs; p = 0.002, p = 0.005, and p = 0.004, respectively. The DS1-treated dogs also had less pneumonitis detected by CT imaging and an increased number of TTF-1 (thyroid transcription factor 1, NKX2-1 positive cells in the bronchioli and alveoli compared to control dogs. Endothelial-like progenitor cells (ELC of host origin, detected by colony assays, were found in peripheral blood after DS1 cell infusion. ELC numbers peaked one day after infusion, and were not detectable by 7 days. These data suggest that infusion of marrow fibroblasts stimulates mobilization of ELC, which is associated with a reduction in otherwise progressive radiation-induced lung injury. We hypothesize that these two observations are related, specifically that circulating ELC contribute to increased angiogenesis, which facilitates endogenous lung repair.

  1. Radioprotective potential of Lagenaria siceraria extract against radiation-induced gastrointestinal injury.

    Science.gov (United States)

    Sharma, Dhara; Goel, Harish Chandra; Chauhan, Sonal

    2016-12-01

    The cucurbits (prebiotics) were investigated as novel agents for radio-modification against gastrointestinal injury. The cell-cycle fractions and DNA damage were monitored in HCT-15 cells. A cucurbit extract was added to culture medium 2 h before irradiation (6 Gy) and was substituted by fresh medium at 4 h post-irradiation. The whole extract of the fruits of Lagenaria siceraria, Luffa cylindrica, or Cucurbita pepo extract enhanced G2 fractions (42%, 34%, and 37%, respectively) as compared with control (20%) and irradiated control (31%). With cucurbits, the comet tail length remained shorter (L. siceraria, 28 μm; L. cylindrica, 34.2 μm; C. pepo, 36.75 μm) than irradiated control (41.75 μm). For in vivo studies, L. siceraria extract (2 mg/kg body weight) was administered orally to mice at 2 h before and 4 and 24 h after whole-body irradiation (10 Gy). L. siceraria treatment restored the glutathione contents to 48.8 μmol/gm as compared with control (27.6 μmol/gm) and irradiated control (19.6 μmol/gm). Irradiation reduced the villi height from 379 to 350 μm and width from 54 to 27 μm. L. siceraria administration countered the radiation effects (length, 366 μm; width, 30 μm, respectively) and improved the villi morphology and tight junction integrity. This study reveals the therapeutic potential of cucurbits against radiation-induced gastrointestinal injury.

  2. Applications of acoustic radiation force impulse quantification in chronic kidney disease: A review

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Liang [Dept. of Ultrasound, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing (China)

    2016-08-15

    Acoustic radiation force impulse (ARFI) imaging is an emerging technique with great promise in the field of elastography. Previous studies have validated ARFI quantification as a method of estimating fibrosis in chronic liver disease. Similarly, fibrosis is the principal process underlying the progression of chronic kidney disease, which is the major cause of renal failure. However, the quantification of tissue stiffness using ARFI imaging is more complex in the kidney than in the liver. Moreover, not all previous studies are comparable because they employed different procedures. Therefore, subsequent studies are warranted, both in animal models and in clinical patients, in order to better understand the histopathological mechanisms associated with renal elasticity and to further improve this imaging method by developing a standardized guidelines for its implementation.

  3. Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report.

    Science.gov (United States)

    Portas, M; Mansilla, E; Drago, H; Dubner, D; Radl, A; Coppola, A; Di Giorgio, M

    2016-09-01

    Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy.

  4. Coping with chronic pain among younger, middle-aged, and older adults living with neurological injury and disease.

    Science.gov (United States)

    Molton, Ivan; Jensen, Mark P; Ehde, Dawn M; Carter, Gregory T; Kraft, George; Cardemas, Diana D

    2008-01-01

    Objective. This article compares use of pain coping strategies among older, middle-aged, and younger adults living with chronic pain and seeks to determine whether the relationship between pain severity and coping is moderated by age. Method. Participants were 464 adults reporting chronic pain secondary to multiple sclerosis, spinal cord injury, or neuromuscular disease. Participants completed a survey including measures of pain severity and the Chronic Pain Coping Inventory. Results. After controlling for clinical and demographic variables, older adults (older than 60) reported a wider range of frequently used strategies and significantly more frequent engagement in activity pacing, seeking social support, and use of coping self-statements than did younger or middle-aged adults. Moderation analyses suggest that, for younger adults, efforts at coping generally increased with greater pain severity, whereas this relationship did not exist for older adults. Discussion. These data suggest differences in the quantity and quality of pain coping among age groups.

  5. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

    1995-12-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

  6. White Matter Abnormalities are Associated with Chronic Postconcussion Symptoms in Blast-Related Mild Traumatic Brain Injury

    Science.gov (United States)

    Miller, Danielle R.; Hayes, Jasmeet P.; Lafleche, Ginette; Salat, David H.; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are non-specific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of co-morbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans were assigned to one of three groups including a blast-exposed no-TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI−LOC), and a blast-related mTBI with LOC group (mTBI+LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI+LOC group had more spatially heterogeneous white matter abnormalities than those in the no-TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI+LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. PMID:26497829

  7. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    Science.gov (United States)

    Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.

  8. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Suk Chul [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Lee, Kyung-Mi [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kang, Yu Mi [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Kwanghee [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Chong Soon [Department of Nuclear Medicine, Haeundae Paik Hospital, Inje University, Busan 612-030 (Korea, Republic of); Kim, Hee Sun, E-mail: hskimdvm@khnp.co.kr [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of)

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  9. Post-traumatic stress in patients with injury-related chronic pain participating in a multimodal pain rehabilitation program

    Directory of Open Access Journals (Sweden)

    Britt-Marie Stålnacke

    2010-03-01

    Full Text Available Britt-Marie Stålnacke, Anna ÖstmanDepartment of Community Medicine and Rehabilitation, Umeå University, SwedenAim: To investigate post-traumatic stress, pain intensity, depression, and anxiety in patients with injury-related chronic pain before and after participating in multimodal pain rehabilitation.Methods: Twenty-eight patients, 21 women and seven men, who participated in the multimodal rehabilitation programs (special whiplash program for whiplash injuries within 1.5 years after the trauma or ordinary program answered a set of questionnaires to assess post-traumatic stress (Impact of Event Scale [IES], pain intensity [Visual Analogue Scale (VAS], depression, and anxiety (Hospital Anxiety and Depression Scale [HAD] before and after the programs.Results: Both pain intensity and post-traumatic stress decreased significantly after the rehabilitation programs in comparison with before (VAS: 57.8 ± 21.6 vs. 67.5 ± 21.9; P = 0.009, IES total score 21.8 ± 13.2 vs. 29.5 ± 12.9; P < 0.001. Patients younger than 40 years reported a statistically higher level of post-traumatic stress compared with patients older than 40 years both before (P = 0.037 and after rehabilitation (P = 0.023. No statistically significant differences were found on the HAD scores.Conclusion: The multimodal rehabilitation programs were effective in reducing both pain intensity and post-traumatic stress. The experience of higher levels of post-traumatic stress in younger persons has to be taken into account when managing patients with injury-related chronic pain.Keywords: post-traumatic, stress disorder, chronic pain, whiplash injuries

  10. SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury.

    Science.gov (United States)

    Niswander, Lisa M; Fegan, Katherine H; Kingsley, Paul D; McGrath, Kathleen E; Palis, James

    2014-07-10

    Megakaryocyte (MK) development in the bone marrow progresses spatially from the endosteal niche, which promotes MK progenitor proliferation, to the sinusoidal vascular niche, the site of terminal maturation and thrombopoiesis. The chemokine stromal cell-derived factor-1 (SDF-1), signaling through CXCR4, is implicated in the maturational chemotaxis of MKs toward sinusoidal vessels. Here, we demonstrate that both IV administration of SDF-1 and stabilization of endogenous SDF-1 acutely increase MK-vasculature association and thrombopoiesis with no change in MK number. In the setting of radiation injury, we find dynamic fluctuations in marrow SDF-1 distribution that spatially and temporally correlate with variations in MK niche occupancy. Stabilization of altered SDF-1 gradients directly affects MK location. Importantly, these SDF-1-mediated changes have functional consequences for platelet production, as the movement of MKs away from the vasculature decreases circulating platelets, while MK association with the vasculature increases circulating platelets. Finally, we demonstrate that manipulation of SDF-1 gradients can improve radiation-induced thrombocytopenia in a manner additive with earlier TPO treatment. Taken together, our data support the concept that SDF-1 regulates the spatial distribution of MKs in the marrow and consequently circulating platelet numbers. This knowledge of the microenvironmental regulation of the MK lineage could lead to improved therapeutic strategies for thrombocytopenia.

  11. Chronic oxidative stress after irradiation: an unproven hypothesis

    Science.gov (United States)

    Cohen, Samuel R; Cohen, Eric P

    2012-01-01

    Injury and organ failure after irradiation of late-responding tissues is a substantial problem in radiation oncology and a major threat after accidental or belligerent exposures. The mechanisms of injury may include death of clonogens, vascular injury, activation of cytokine networks, and/or chronic oxidative stress. Knowledge of mechanisms may guide optimal use of mitigators. The hypothesis of chronic oxidative stress as a mechanism of late radiation injury has received much attention. We review herein the published evidence for chronic oxidative stress in vivo, and for use of antioxidants as mitigators of normal tissue radiation injury. We conclude that there is only indirect evidence for chronic oxidative stress after irradiation, and there are only limited published reports of mitigation by antioxidants. We did not find a differentiation of persistent markers of oxidative stress from an ongoing production of oxygen radicals. It is thus unproven that chronic oxidative stress plays a major role in causing radiation injury and organ failure in late-responding tissues. Further investigation is justified, to identify persistent oxidative stress and to identify optimal mitigators of radiation injury. PMID:23245910

  12. Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

    Institute of Scientific and Technical Information of China (English)

    Duo-Yi Li; Lan Meng; Nan Ji; Fang Luo

    2015-01-01

    Background:Pulsed radiofrequency (PRF) application to the dorsal root ganglia can reduce neuropathic pain (NP) in animal models,but the effect of PRF on damaged peripheral nerves has not been examined.We investigated the effect of PRF to the rat sciatic nerve (SN) on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI).Methods:The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL).Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group.The contralateral SN served as a control.The MWT and TWL were determined again 2,4,6,8,10,12,and 14 days after the PRF or sham treatment.On day 14,ipsilateral and contralateral common SNs were excised and examined by electron microscopy.Results:Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P =0.000).In the PRF group,MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P =0.000),while no such difference was observed in the sham group (P > 0.05).Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group.Conclusions:Hyperalgesia is relieved,and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP.

  13. Safety and efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in chronic allograft injury

    Directory of Open Access Journals (Sweden)

    P R Shah

    2011-01-01

    Full Text Available Angiotensin II plays a crucial role in the development of chronic allograft injury (CAI. Clinical experience with angiotensin converting enzyme inhibitor (ACEI and angiotensin receptor blockade (ARBS in CAI has unfortunately been limited. We carried out a prospective one year single center case controlled study to analyze the effect of ACEI /ARBS on the progression of CAI and in decreasing proteinuria. One hundred patients with CAI were evaluated. Of the 100 patients, 50 were selected to receive ACEI/ ARBS (group 1 and 50 managed without ACEI/ARBS (group 2. Their remaining management was similar in both the groups. Patients with hyperkalemia, history of allergic reactions, ACEI/ARBS intake and pregnancy were excluded. Average time for development of CAI was 19.6 ± 12.7 months in group 1 vs. 20.8 ± 12.8 in group 2. In group 1, mean systolic/diastolic BP was 136/82 mmHg at the time of establishment of CAI and 124/76 mmHg at the end of one year, and in group 2, it was 138/86 mmHg vs. 126/80 mmHg, respectively. Mean glomerular filtration rate (GFR was 48.78 ± 13.4 in the former vs. 44.23 ± 8.14 in the latter. ACEI/ARBS administration was associated with stabilization of serum creatinine. GFR was maintained up to one year after CAI. Group 1 had a decrease in proteinuria by 1.41 g/day as compared with group 2 with proteinuria of 0.83 g/day. ACEI/ARBS administration is beneficial in CAI for BP control and significant decrease in proteinuria along with the stabilization of graft function.

  14. Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Duo-Yi Li

    2015-01-01

    Full Text Available Background: Pulsed radiofrequency (PRF application to the dorsal root ganglia can reduce neuropathic pain (NP in animal models, but the effect of PRF on damaged peripheral nerves has not been examined. We investigated the effect of PRF to the rat sciatic nerve (SN on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI. Methods: The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT and thermal withdrawal latency (TWL. Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group. The contralateral SN served as a control. The MWT and TWL were determined again 2, 4, 6, 8, 10, 12, and 14 days after the PRF or sham treatment. On day 14, ipsilateral and contralateral common SNs were excised and examined by electron microscopy. Results: Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P = 0.000. In the PRF group, MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P = 0.000, while no such difference was observed in the sham group (P > 0.05. Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group. Conclusions: Hyperalgesia is relieved, and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP.

  15. Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury.

    Science.gov (United States)

    Leedom, Alexander J; Sullivan, Aaron B; Dong, Baiyan; Lau, Denise; Gronert, Karsten

    2010-01-01

    Inflammation and angiogenesis are intimately linked, and their dysregulation leads to pathological angiogenesis in human diseases. 15-lipoxygenase (15-LOX) and lipoxin A(4) receptors (ALX) constitute a LXA(4) circuit that is a key feature of inflammatory resolution. LXA(4) analogs have been shown to regulate vascular endothelial growth factor (VEGF)-A-induced angiogenic response in vitro. 15-LOX and ALX are highly expressed in the avascular and immune-privileged cornea. However, the role of this endogenous LXA(4) circuit in pathological neovascularization has not been determined. We report that suture-induced chronic injury in the cornea triggered polymorphonuclear leukocytes (PMN) infiltration, pathological neovascularization, and up-regulation of mediators of inflammatory angiogenesis, namely VEGF-A and the VEGF-3 receptor (FLT4). Up-regulation of the VEGF circuit and neovascularization correlated with selective changes in both 15-LOX (Alox15) and ALX (Fpr-rs2) expression and a temporally defined increase in basal 15-LOX activity. More importantly, genetic deletion of 15-LOX or 5-LOX, key and obligatory enzymes in the formation of LXA(4), respectively, led to exacerbated inflammatory neovascularization coincident with increased VEGF-A and FLT4 expression. Direct topical treatment with LXA(4), but not its metabolic precursor 15-hydroxyeicosatetraenoic acid, reduced expression of VEGF-A and FLT4 and inflammatory angiogenesis and rescued 15-LOX knockout mice from exacerbated angiogenesis. In summary, our findings and the prominent expression of 15-LOX and ALX in epithelial cells and macrophages place the LXA(4) circuit as an endogenous regulator of pathological angiogenesis.

  16. Nociceptors as chronic drivers of pain and hyperreflexia after spinal cord injury: an adaptive-maladaptive hyperfunctional state hypothesis

    Directory of Open Access Journals (Sweden)

    Edgar T Walters

    2012-08-01

    Full Text Available Spinal cord injury (SCI causes chronic peripheral sensitization of nociceptors and persistent generation of spontaneous action potentials (SA in peripheral branches and the somata of hyperexcitable nociceptors within dorsal root ganglia (DRG. Here it is proposed that SCI triggers in numerous nociceptors a persistent hyperfunctional state (peripheral, synaptic, and somal that originally evolved as an adaptive response to compensate for loss of sensory terminals after severe but survivable peripheral injury. In this hypothesis, nociceptor somata monitor the status of their own receptive field and the rest of the body by integrating signals received by their peripheral and central branches and the soma itself. A nociceptor switches into a potentially permanent hyperfunctional state when central neural, glial, and inflammatory signal combinations are detected that indicate extensive peripheral injury. Similar signal combinations are produced by SCI and disseminated widely to uninjured as well as injured nociceptors. This paper focuses on the uninjured nociceptors that are altered by SCI. Enhanced activity generated in below-level nociceptors promotes below-level central sensitization, somatic and autonomic hyperreflexia, and visceral dysfunction. If sufficient ascending fibers survive, enhanced activity in below-level nociceptors contributes to below-level pain. Nociceptor activity generated above the injury level contributes to at- and above-level sensitization and pain (evoked and spontaneous. Thus, SCI triggers a potent nociceptor state that may have been adaptive (from an evolutionary perspective after severe peripheral injury but is maladaptive after SCI. Evidence that hyperfunctional nociceptors make large contributions to behavioral hypersensitivity after SCI suggests that nociceptor-specific ion channels required for nociceptor SA and hypersensitivity offer promising targets for treating chronic pain and hyperreflexia after SCI.

  17. Effect of BMPs on hematopoietic injury of acute radiation sickness in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tian Qiong; Zhang Shaozhang; Pu Qin; Zhang Fake [Fourth Military Medical University, Xi' an Shaanxi (China); Hannah, X.H. [Department of Biochemistry, Hong Kong Science and Technology, Hong Kong (China)

    2000-05-01

    The purpose of this paper is to investigate the effect of Bone morphogenetic proteins (BMPs) on hematopoietic acute radiation sickness in mice. BMP, rhBMP-2m and PBK/hBMP-2-NIH3T3 cells were obtained separately by chemistry, molecule biological method and genetherapy method. In this study, the effect of BMPs on hematopoiesis was detected at postirradiation: some hematological parameters, 30 days the survival ratio and formation of bone marrow CFU-GM colony. The experiments indicate that when phBMP (purified bovine bone morphogenetic protein) can increase the formation of bone narrow CFU-GM colony (p<0.05) at 10th d after irradiation. Irradiation control group's mice died in 30 days, but effect of rhBMP-2m on the survival of mice after 7.5Gy irradiation, was detected whereas there were 10%, 15% and 35% all mice of survived after injection i.p. with 0.5 mg, 1.0 mg and 2.0 mg of rhBMP-2m respectively. All hematological parameters of treated mice were significantly higher than control group (p<0.01). PBK/hBMP-2-NIH3T3 cells were established and transplanted into mice irradiated by 7.0Gy r ray by i.p., the survival ratio of treated mice higher than negative control group (p<0.01), and all hematopoietic parameters were increased statistically significant (p<0.01). These data support the our hypothesis: BMPs can treat the acute radiation sickness. The results indicate that in adult mice, BMPs can recover or treat the hematopoietic injury of acute radiation sickness in mice. (author)

  18. Neuronal injury in the motor cortex after chronic stroke and lower limb motor impairment:a voxel-based lesion symptom mapping study

    Institute of Scientific and Technical Information of China (English)

    Alexandria M. Reynolds; Denise M. Peters; Jennifer M. C. Vendemia; Lenwood P. Smith; Raymond C. Sweet; Gordon C. Baylis; Debra Krotish; Stacy L Fritz

    2014-01-01

    Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuro-nal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deifcits expected after damage to the cortical motor system due to stroke. These ifndings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.

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

    Science.gov (United States)

    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.

  20. Treatment and long-term outcome of chronic radiation esophagitis after radiation therapy for head and neck tumors: A report of 13 cases

    Energy Technology Data Exchange (ETDEWEB)

    Silvain, C.; Barrioz, T.; Besson, I.; Babin, P.; Fontanel, J.P.; Daban, A.; Matuchansky, C.; Beauchant, M. (CHU J Bernard, Poitiers (France))

    1993-05-01

    The natural history of chronic radiation esophagitis occurring in previously normal esophagus is still unknown. The authors describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2--120 months) after the end of radiation for pyriform fossae carcinoma (N = 5), tonsil carcinoma (N = 2), larynx carcinoma (N = 2), pharynx carcinoma (N = 2), base of the tongue (N = 1), and thyroid carcinomas (N = 1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and surgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatations. These treatments allowed nearly normal oral diet in 11/13 patients. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after six months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding. In conclusion, chronic radiation esophagitis is a severe disease with an underestimated frequency. In this study, peroral dilatations appeared to be necessary and were not associated with an increased morbidity. 21 refs., 1 tab.

  1. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation.

    Science.gov (United States)

    Rybkina, Valentina L; Azizova, Tamara V; Scherthan, Harry; Meineke, Viktor; Doerr, Harald; Adamova, Galina V; Teplyakova, Olga V; Osovets, Sergey V; Bannikova, Maria V; Zurochka, Alexander V

    2014-11-01

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  2. Experimental studies on pathogenesis of the brain radiation injury in early stage

    Energy Technology Data Exchange (ETDEWEB)

    Ye Tian [Suzhou Medical Coll., Jiangsu (China). 2nd Affiliated Hospital; Shiyao Bao; Weibo Yin; Chunfeng Liu; Zhilin Zhang

    2000-05-01

    To investigate the pathogenesis of the brain radiation injury in the early stage, a series of experiments were performed as below. The SD rats halfbrain were irradiated by the single dose of 10, 20, and 30 Gy of 4 MeV electron, all those experiments were performed in 1 day to 3 months after radiation. The neurological symptoms, the weight and the skin response inside the field of all the rats were evaluated sequentially. The measurement of regional cerebral blood flow (rCBF) using hydrogen gas generated by electrolysis, the calculation of the brain water content percentage with wet-dry weight formula. The DNA contents and the quantities of bcl-2 protein were analyzed by flow cytometry. The brain histological sections were scanned to assess the present or absence of white matter necrosis in the region of hippocampus, and then the hippocampus region was observed for the morphological changes of the blood vessel, neuroglial, and the neurons. Some of the data were analyzed by the Student t test. Intra-portal alopecia was observed in all rats which received 30 Gy and some rats which received 20 Gy, the abnormal neurological signs were not found in all the rats, but the tend of weight increase was less pronounced in 1-3 months in the irradiated rats than those unirradiated. By comparison the unirradiated hemisphere, the rCBF of the contralateral brain decreased in most of the rats. In 20 Gy and 30 Gy groups, rCBF decreased areas expand gradually along with the prolong of observation time, from the nucleus caudate putamen, to the frontal cortex and then the hippocampus, the rCBF of whole the irradiated hemibrain was reduced significantly at 3 month after radiation. The water content of the irradiated halfbrain increased progressively, it means the brain edema exists in the meantime. By comparison the unirradiation halfbrain, the apoptosis of the hippocampus cells in the irradiated brain increased, and the expression of bcl-2 protein decreased at the meantime, and those

  3. Basic research of the relationship between irradiation dose and volume in radiation-induced pulmonary injury

    Institute of Scientific and Technical Information of China (English)

    PANG Qing-song; WANG Ping; WANG Jing; WANG Wei; WANG Jun; YUAN Zhi-yong

    2009-01-01

    Background Irradiation dose and volume are the major physical factors of radiation-induced lung injury.The study investigated the relationships between the irradiation dose and volume in radiation-induced lung injury by setting up a model of graded volume irradiation of the rat lung.Methods Animals were randomly assigned to three groups.The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume.The treatment plan for the three groups was:group 1 received a "high dose to a small volume" (25% volume group) with the mean irradiation volume being 1.748 cm3 (25% lung volume);the total dose and mean lung dose (MLD) were 4610 cGy and 2006 cGy,respectively (bilateral AP-PA fields,source to axis distance (SAD)=100 cm,6MVX,single irradiation);Group 2 received a "low dose to a large volume" (100% volume group) with the mean irradiation volume being 6.99 cm3 (100% lung volume);the total dose was 1153 cGy.MLD was 2006 cGy,which was the same as that of group 1 (bilateral AP-PA fields,SAD = 100 cm,6MVX,single irradiation);Group 3 was a control group.With the exception of receiving no irradiation,group 3 had rest steps that were the same as those of the experimental groups.After irradiation,functional,histopathological,and CT changes were compared every two weeks till the 16th week.Results Functionally,after irradiation breath rate (BR) increases were observed in both group 1 and group 2,especially during the period of 6th-8th weeks.The changes of BR in the 100% volume group were earlier and faster.For the 25% volume group,although pathology was more severe,hardly any obvious increase in BR was observed.Radiographic changes were observed during the early period (the 4th week) and the most obvious changes manifested during the mediated period (the 8th week).The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group,and ground glass opacity and patchy consolidation were presented in the 25

  4. ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL

    Science.gov (United States)

    de OLIVEIRA, Valter Oberdan Borges; OLIVEIRA, Juliana Passos Rocha; de FRANÇA, Eloy Vianey Carvalho; BRITO, Hugo Leite de Farias; NASCIMENTO, Tereza Virgínia; FRANÇA, Alex

    2016-01-01

    SUMMARY Introduction: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(-) chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. Methods: Patients presenting HBsAg(+) for more than six months, Anti-HBe(+)/HBeAg(-), viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F ≥ 2 and/or A ≥ 2 by the METAVIR classification. Results: 11/27 (40.7%) patients had advanced liver injury, with a mean viral load of 701.0 (± 653.7) IU/mL versus 482.8 (± 580.0) IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37). The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. Conclusions: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment. PMID:27680170

  5. ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL

    Directory of Open Access Journals (Sweden)

    Valter Oberdan Borges de OLIVEIRA

    Full Text Available SUMMARY Introduction: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(- chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. Methods: Patients presenting HBsAg(+ for more than six months, Anti-HBe(+/HBeAg(-, viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F ≥ 2 and/or A ≥ 2 by the METAVIR classification. Results: 11/27 (40.7% patients had advanced liver injury, with a mean viral load of 701.0 (± 653.7 IU/mL versus 482.8 (± 580.0 IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37. The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. Conclusions: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment.

  6. Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE−/− Alzheimer mouse model

    DEFF Research Database (Denmark)

    Kempf, Stefan; Janik, Dirk; Barjaktarovic, Zarko

    2017-01-01

    Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumula......Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days...... with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer´s model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates. The radiation-induced changes in the phosphoproteome were associated with the control...... that several molecular targets induced by chronic low-dose-rate radiation overlap with those of Alzheimer´s pathology. It may suggest that ionising radiation functions as a contributing risk factor to this neurodegenerative disease....

  7. Effects of chronic shoulder pain on quality of life and occupational engagement in the population with chronic spinal cord injury: preparing for the best outcomes with occupational therapy.

    Science.gov (United States)

    Silvestri, Jennifer

    2017-01-01

    Purpose To examine the implications of chronic shoulder pain on quality of life and occupational engagement in spinal cord injury (SCI). The Ecology of Human Performance Model and Self-Efficacy Theory will be used to further examine the interplay of shoulder pain, quality of life and engagement in this population. Method Analysis of literature. Results Persons with SCI have a high prevalence of shoulder pain and injury, affecting 37-84% of analysed studies; chronic pain limits occupational engagement and decreases quality of life. Remediation of pain provides improved occupational engagement, functional independence and quality of life in those with high self-efficacy and low depression. Conclusion Shoulder pain is a serious complication following SCI and the Ecology of Human Performance Model and Self-Efficacy Theory can be utilized in conjunction for a framework to evaluate, treat and prevent shoulder pain and its devastating effects on occupational engagement and quality of life in the spinal cord injured population. Thereafter, rehabilitation professionals will have a greater understanding of these interactions to serve as a guide for evaluation and intervention planning to promote optimal occupational engagement through limiting the experiences of occupational injustices for those with SCI and shoulder pain. Implications for Rehabilitation Musculoskeletal pain at the shoulder joint and depression are common complications following spinal cord injury that limit occupational engagement and decrease quality of life. To increase engagement and quality of life in this population, treatments need to address all factors including the under-lying psychosocial instead of task and environment modification alone. The Ecology of Human Performance Model and Self-efficacy Theory are effective frameworks that can be used for evaluation, treatment planning and outcome measurement to maximize occupational engagement and quality of life.

  8. Three months of chronic ethanol administration and the behavioral outcome of rats after lateral fluid percussion brain injury.

    Science.gov (United States)

    Masse, J; Billings, B; Dhillon, H S; Mace, D; Hicks, R; Barron, S; Kraemer, P J; Dendle, P; Prasad, R M

    2000-05-01

    This study examined the effects of 3 months of chronic ethanol administration (CEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 3 months. Then, rats from both diet groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. Postinjury behavioral measurements revealed that brain injury caused significant spatial learning disability in both diet groups. There were no significant differences in spatial learning ability in the sham or brain-injured animals between the control and ethanol diets. However, a trend towards cognitive impairment in the sham animals and a trend towards reduced deficits in the brain-injured animals were observed in the ethanol diet group. Histologic analysis of injured animals from both diet groups revealed similar extents of ipsilateral cortical and hippocampal CA3 damage. These results, in general, suggest that 3 months of CEAn does not significantly alter the behavioral and morphologic outcome of experimental brain injury.

  9. Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Shi-Bing Su; Qing-Ya Li; Zhi-Zhong Guo; Yan Guan; Jia Du; Yi-Yu Lu; Yi-Yang Hu; Ping Liu; Shuang Huang

    2012-01-01

    AIM:To investigate whether circulating microRNAs (miRNAs) can serve as molecular markers to predict liver injury resulted from chronic hepatitis B (CHB).METHODS:The profiles of serum miRNA expression were first generated with serum samples collected from 10 patients with CHB and 10 healthy donors (Ctrls) by microarray analysis.The levels of several miRNAs were further quantitated by real-time reverse transcription polymerase chain reaction with serum samples from another 24 CHB patients and 24 Ctrls.Serum samples of 20 patients with nonalcohlic steatohepatitis (NASH) were also included for comparison.The comparison in the levels of miRNAs between groups (CHB,NASH and Ctrl) was analyzed with Mann-Whitney U-test.The correlation between miRNAs and clinical pathoparameters was analyzed using Spearman correlation analysis or canonical correlation analysis.The receiver-operator characteristic (ROC) curves were also generated to determine the specificity and sensitivity of each individual miRNA in distinguishing patients with CHB from Ctrls.RESULTS:miRNA profile analysis showed that 34 miRNAs were differentially expressed between CHB and Ctrl subjects,in which 12 were up-regulated and 22 down-regulated in CHB subject (fold change > 2.0 and P < 0.01).The median levels of miR-122,-572,-575 and-638 were significantly higher (P < 1.00 × 10-5) while miR-744 significantly lower (P < 1.00 × 10-6) in CHB compared with the Ctrl.The levels of miR-122,-572 and-638 were also higher (P < 1.00 × 10-3) while the level of miR-744 lower in CHB (P < 0.05) than in NASH,although the difference between them was not as significant as that between CHB and Ctrl.ROC curve analysis revealed that the levels of miR-122,-572,-575,-638 and-744 in serum were sensitive and specific enough to distinguish CHB,NASH and Ctrl.Multivariate analysis further showed that the levels of these miRNAs were correlated with the liver function parameters.Most significantly,it was the scatter plot of

  10. Concussion/mild traumatic brain injury-related chronic pain in males and females: A diagnostic modelling study

    Science.gov (United States)

    Mollayeva, Tatyana; Cassidy, J. David; Shapiro, Colin M.; Mollayeva, Shirin; Colantonio, Angela

    2017-01-01

    Abstract Pain is an unpleasant, complex, and perceived experience that places a significant burden on patients and clinicians. Its severity may be mediated by emotion, attitude, and environmental influences, and pain may be expressed differently in males and females. Traumatic brain injury (TBI) is frequently associated with chronic pain. This diagnostic modeling study examined sex differences in the construct of chronic pain in patients with delayed recovery from concussion/mild traumatic brain injury (mTBI). Data were collected from standardized questionnaires, neuroimaging records, and comprehensive clinical assessments. Bivariate associations were calculated using the Spearman correlation coefficient or analysis of variance. We established sex-specific stepwise multivariate linear regression models of factors associated with pain. Of the 94 participants diagnosed with mTBI (the mean age was 45.20 ± 9.94 years; 61.2% were males; the median time since injury was 197 days [interquartile range 139–416]), head/neck, and bodily pain were reported by 93% and 64%, respectively. No sex differences were identified in pain frequencies or severity. Pain was significantly associated with certain socio-demographic, injury-related, behavioral, and clinical variables. In the multivariable regression analysis, several determinants explained 60% of the pain variance in males and 46% in females. Pain is common in patients with delayed recovery from mTBI and is significantly associated with potentially modifiable clinical and nonclinical variables. Examining the multidimensional construct of pain in concussion/mTBI through a sex lens garners new directions for future longitudinal research on the pain mechanisms involved in postconcussion syndrome. PMID:28207508

  11. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Charles W. Wilkinson

    2012-02-01

    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  12. Chronic Post-Traumatic Headache after Head Injury in Children and Adolescents

    Science.gov (United States)

    Kirk, Charlotte; Nagiub, George; Abu-Arafeh, Ishaq

    2008-01-01

    This was a prospective, observational study of children aged 3 to 15 years admitted to hospital with head injury (HI). Demographic data and information on the nature of the HI, and history of premorbid headache were collected. A structured telephone questionnaire was used to interview parents and children 2 months after injury and at 4-monthly…

  13. Chronic angiotensin (1-7) injection accelerates STZ-induced diabetic renal injury

    Institute of Scientific and Technical Information of China (English)

    Ying SHAO; Ming HE; Li ZHOU; Tai YAO; Yu HUANG; Li-min LU

    2008-01-01

    Aim: The renin-angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angio-tensin (Ang) (1-7) has been reported to counteract the effects of Ang Ⅱ and was even considered as a new therapeutical target in RAS. The present study aimed to investigate the effect of Ang (1-7) administration on a diabetic animal model and the modulation on local RAS. Methods: Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1-7) treatment [D+Ang(1-7)]. In the D+Ang(1-7) group, a dose of 25 μg-kg-1.h-1 of Ang (1-7) was continually injected through the jugular vein by embedding mini-osmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang Ⅱ levels were measured by radioimmunoassay. Ang-con-verting enzyme (ACE), ACE2, Ang Ⅱ type 1 (AT1) receptor, Ang Ⅱ type 2 (AT2) receptor, Ang (1-7) Mas receptor, and TGF-β1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF-β1 protein levels were analyzed by Western blotting. Results: The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1-7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-β1 mRNA and protein levels were elevated in the D+Ang(1-7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1-7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1-7)-injected group, while the number of AT2 and Mas receptors decreased. Conclusion: Exogenous Ang (1-7) injection did not

  14. Radiation enteritis

    Science.gov (United States)

    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 ...

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

    Science.gov (United States)

    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.

  16. Rehabilitation needs and participation restriction in patients with cognitive disorder in the chronic phase of traumatic brain injury

    Science.gov (United States)

    Sashika, Hironobu; Takada, Kaoruko; Kikuchi, Naohisa

    2017-01-01

    Abstract The purpose of this study was to clarify psychosocial factors/problems, social participation, quality of life (QOL), and rehabilitation needs in chronic-phase traumatic brain injury (TBI) patients with cognitive disorder discharged from the level-1 trauma center (L1-TC), and to inspect the effects of rehabilitation intervention to these subjects. A mixed-method research (cross-sectional and qualitative study) was conducted at an outpatient rehabilitation department. Inclusion criteria of subjects were transfer to the L1-TC due to TBI; acute-stage rehabilitation treatment received in the L1-TC from November 2006 to October 2011; age of ≥18 and social participation, QOL, psychosocial factors/problems, rehabilitation needs, and chronic-phase rehabilitation outcomes were evaluated using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, the Zung Self-Rating Depression Scale, the Sydney Psychosocial Reintegration Scale, Version 2, and the Short Form 36, Version 2, qualitative analysis of semistructured interviews, etc. Participants were classified into achieved-social-participation (n = 11; employed: 8), difficult-social-participation (n = 12; unemployed: 8), and no-cognitive-dysfunction groups (n = 8; no social participation restriction). Relative to the achieved-social-participation group, the difficult-social-participation group showed greater injury and cognitive dysfunction and lower Sydney Psychosocial Reintegration Scale and Short Form 36 role/social component summary scores (64.9/49.1 vs 44.3/30.4, respectively, P social participation status was greatly affected by the later cognitive disorders and psychosocial factors/problems not by the severity of TBI. No changes were observed in these scores following chronic-phase rehabilitation intervention. Chronic-phase TBI with cognitive disorder led to rehabilitation needs, and improvement of subjects’ psychosocial problems and QOL was difficult. PMID

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

    Directory of Open Access Journals (Sweden)

    Deguan Li

    2016-06-01

    Full Text Available 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.

  18. Pulmonary radiation injury manifested by signs of bronchiolitis obliterans with organizing pneumonia after postoperative breast cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ogata, Kenichi; Shibata, Kazumi; Nishio, Tetsuo [Kitakyusyu Municipal Medical Center, Fukuoka (Japan); Kawarada, Yuji; Hara, Nobuyuki

    1999-12-01

    A 67-year-old woman underwent surgery for cancer of both breast (right: mastectomy, left: conserving surgery), and received 60 Gy radiation to the left postoperative breast. Three months later, cough and fever developed. A chest radiograph demonstrated infiltrative shadows in the left lung field. Transbronchial lung biopsy specimens disclosed organizing exudates in the alveolar spaces and bronchioles. After treatment with prednisolone, the clinical symptoms and radiographic infiltrates disappeared. This was a case of pulmonary radiation injury pathologically manifested by signs of bronchiolitis obliterans with organizing pneumonia. (author)

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

    Science.gov (United States)

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

    2014-06-15

    Skin-resident T cells have been shown to play important roles in tissue homeostasis and wound repair, but their role in UV radiation (UVR)-mediated skin injury and subsequent tissue regeneration is less clear. In this study, we demonstrate that acute UVR rapidly activates skin-resident T cells in humans and dendritic epidermal γδ T cells (DETCs) 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 DETCs. IL-17, in turn, induces epidermal TNF-related weak inducer of apoptosis and growth arrest and DNA damage-associated gene 45, two molecules linked to the DNA repair response. Finally, we demonstrate that DETCs and human skin-resident T cells limit DNA damage in keratinocytes. Taken 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.

  20. Chronic alcoholism-mediated impairment in the medulla oblongata: a mechanism of alcohol-related mortality in traumatic brain injury?

    Science.gov (United States)

    Lai, Xiao-ping; Yu, Xiao-jun; Qian, Hong; Wei, Lai; Lv, Jun-yao; Xu, Xiao-hu

    2013-01-01

    Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.

  1. Transgenerational accumulation of radiation damage in small mammals chronically exposed to Chernobyl fallout.

    Science.gov (United States)

    Ryabokon, Nadezhda I; Goncharova, R I

    2006-09-01

    The purpose of this investigation has been the analysis of the long-term development of biological damage in natural populations of a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber), which were chronically exposed to low doses of ionizing radiation over 22 animal generations within 10 years following the Chernobyl accident. The time course of the biological end-points (chromosome aberrations in bone marrow cells and embryonic lethality) was compared with the time course of the whole-body absorbed dose rate from external and internal exposure in the studied populations inhabiting monitoring sites in Belarus with different ground deposition of radionuclides. The yield of chromosome aberrations and, in lesser degree, embryonic lethality was associated with the radionuclide contamination of the monitoring areas in a dose-dependent manner. As a main feature of the long-term development of biological damage under low dose rate irradiation, permanently elevated levels of chromosome aberrations and an increasing frequency of embryonic lethality have developed over 22 animal generations. This contrasts with the assumption that the biological damage would gradually disappear since in the same period of time the whole-body absorbed dose rate decreased exponentially with a half-value time of about 2.5-3 years. Furthermore, gravid females were captured, and their offspring, born and grown up under contamination-free laboratory conditions, showed the same enhanced level of chromosome aberrations. Therefore the authors suggest that, along with the biological damage attributable to the individual exposure of each animal, the observed cellular and systemic effects reflect the transgenerational transmission and accumulation, via genetic and/or epigenetic pathways, of damage attributable to the chronic low-dose rate exposure of the preceding generations of animals. They also suggest that the level of the accumulated transmissible damage in the investigated

  2. State of the art. Four easy pieces: interconnections between tissue injury, intermediary metabolism, autoimmunity, and chronic degeneration.

    Science.gov (United States)

    Steinman, Lawrence

    2006-08-01

    Four questions are posed: (1) Can tissue damage itself provoke autoimmunity? (2) Can genetic mutations of key structures produce tissue pathology and thus provoke autoimmunity? (3) Can acute immune damage produce tissue degeneration without further hallmarks of an immune response? (4) Can intermediary metabolism modulate immune damage to tissues? Four answers are given: (1) Tissue injury itself may lead to autoimmunity. Both innate and adaptive immunity may arise as a response to tissue injury, and the immune attack can further damage tissue. (2) Genetic mutations can lead to an immune response indistinguishable from autoimmunity, exemplified from Duchenne's Muscular Dystrophy and X-linked adrenoleukodystrophy. (3) Chronic immune damage may lead to tissue degeneration, with or without further hallmarks of an immune response. Variations on this theme, including inverse scenarios, are also possible: Inborn errors of metabolism may lead to tissue damage that may provoke an adaptive and or innate immune response. The immune response might further damage tissue. (4) Finally, perturbations of intermediary metabolism may modulate the immune response, controlling the extent of immune-mediated damage. Examples are taken from perturbations in the cholesterol pathway that influence the characteristics of the immune response, and with tryptophan metabolites that modulate autoimmunity and graft rejection. Inflammatory, degenerative, and autoimmune neurological disease will be discussed in terms of their implications for pathogenic mechanisms underlying chronic obstructive pulmonary disease.

  3. Depression, anxiety and quality of life in caregiver spouses of veterans with chronic spinal cord injury

    OpenAIRE

    Mohammad Hosein Ebrahimzadeh; Bibi Soheyla Shojaee; Farideh Golhasani-Keshtan; Fatemeh Moharari; Amir Reza Kachooei; Asieh Sadat Fattahi

    2014-01-01

    Objective: We were curious about the degree of anxiety and depression and their effect on the quality of life of the caregivers of veterans with spinal cord injury (SCI). Methods: A convenience sample of 72 out of 120 caregiver spouses of veterans with spinal cord injury participated in our study. The Hospital Anxiety and Depression Scale (HADS) were considered as a measure of depression and anxiety. The World Health Organization Quality of Life BREF questionnaire (WHOQOL-BREF) was considered...

  4. EFFECT OF CHRONIC RADIATION ON PLANT-PATHOGEN INTERACTIONS IN 30-KM CHERNOBYL ZONE

    Directory of Open Access Journals (Sweden)

    Dmitriev A.

    2012-08-01

    Full Text Available It was established in pot experiments that infection with powdery mildew (Erysiphe graminis DC. f. sp. tritici Em. Marchal and brown rust (Puccinia triticana Erikss. & Henn. of three wheat (Triticum aestivum L. cultivars ('Mironovskaya 808', 'Polesskay 70', and 'Kiyanka' grown from seeds, collected in the Chernobyl exclusion zone, was 1.5–2.0 times higher than that of plants grown from control seeds. On filed plots in the Chernobyl zone, wheat plant resistance to biotic stress was reduced. At artificial infection with brown rusts, the disease development was enhanced on plots with increased radiation background. One of the mechanisms of declined phytoimmunity potential under the action of low doses of chronic irradiation is evidently a reduced activity of plant proteinase inhibitors. Thus, in wheat and rye (Secale cereale L., cv. ‘Saratovskaya’ kernels, their activity reduced by 35–60% as compared to control. Active form and race formation in the population of the grass stem rust causal agent (Puccinia graminis Pers. was observed in the Chernobyl zone. A “new” population of this fungus with high frequency of more virulent clones than in other Ukraine regions was distinguished. The results obtained independently in greenhouse and field trials performed in the Chernobyl zone demonstrated radiation stress influence on the pathogen–plant system. They indicate a necessity of monitoring the microevolutionary processes occurring in both plants and their pathogens under conditions of technogenic stresses.

  5. Response of shortgrass Plains vegetation to chronic and seasonally administered gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fraley, L. Jr.

    1971-08-01

    In order to determine the effect of radiation on the structure of native shortgrass plains vegetation, an 8750 Ci 137Cs source was installed on the Central Plains Experimental Range near Nunn, Colorado; The experimental area was divided into 6 treatment sectors, a control, 2 sectors for chronic exposure (irradiation initiated April 1969 and continuing as of August 1971), and one each for spring, summer and late fall seasonal semi-acute (30 day), exposures which were administered during April, July and December, 1969, respectively. Community structure was measured by coefficient of community and diversity index. Yield was determined by clipping plots in September 1970 and visual estimates in September 1969 and 1970 for the grass-sedge component of the vegetation. Individual species sensitivity was determined by density data recorded in April, June and September of 1969 and 1970 and by a phenological index recorded at weekly intervals during the 1969 and 1970 growing seasons. The response of the vegetation was similar whether determined by coefficient of community or diversity with diversity being a more sensitive measure of effects. In the chronically exposed sectors, the exposure rate which resulted in a 50 per cent reduction in these 2 parameters (CC50 or D50) was still decreasing the second growing season and was approximately 18 R/hr for the CC50 as of June 1970 and 10 R/hr for the D50 as of September 1970. For the seasonally exposed sectors, the late fall period (December, 1969) was the most sensitive, summer (July, 1969) the least sensitive and spring (April, 1969) intermediate with CC50 and D50 values of 195 and 90, 240 and 222, and 120 and 74 R/hr for the spring, summer and late fall exposed sectors, respectively. Yield and density data indicated a rapid revegetation of the spring and summer exposed sectors during 1970 as a result of an influx of invader species such as Salsola kali tenuifolia, Chenopodium leptophyllum and Lepidium densiflorum and the

  6. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Lihua [Department of Radiation Oncology, The First Hospital of Jilin University, Changchun (China); Cui, Jingkun [Department of Internal Medicine, Nanling School District Hospital of Jilin University, Changchun (China); Tang, Fengjiao; Cong, Xiaofeng [Cancer Center, The First Hospital of Jilin University, Changchun (China); Han, Fujun, E-mail: fujun_han@aliyun.com [Cancer Center, The First Hospital of Jilin University, Changchun (China)

    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. Reliability of dynamic sitting balance tests and their correlations with functional mobility for wheelchair users with chronic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Kelly L. Gao

    2015-01-01

    Full Text Available The purpose of this study is to develop a reliable and valid tool for measuring the dynamic sitting balance of wheelchair users with spinal cord injury. The balance tests were performed in nine patients with chronic spinal cord injury (average of 17.2 years postinjury between levels C6 and L1, while they were sitting in their wheelchairs and on a standardized stool (unsupported sitting, twice, 7 days apart. Limits of stability (LOS and sequential weight shifting (SWS were designed in this study. The balance tests measured participants' volitional weight shifting in multiple directions within their base of support. Their mobility scores on the Spinal Cord Independence Measure III were correlated with the balance test results. The LOS results showed moderate to excellent test–retest reliability (intraclass correlation coefficients ranged from 0.673 to 0.990 for both the wheelchair and the unsupported sitting. The SWS results showed moderate to excellent reliability (intraclass correlation coefficients ranged from 0.688 to 0.952. The LOS results correlated significantly with the Spinal Cord Independence Measure III mobility scores only in case of unsupported sitting, but the SWS test results showed significant correlations in both sitting conditions. To sum up, the sitting LOS and SWS tests are reliable and valid tools for assessing the dynamic sitting balance control of patients with spinal cord injury.

  8. Acute Kidney Injury: Tubular Markers and Risk for Chronic Kidney Disease and End-Stage Kidney Failure.

    Science.gov (United States)

    Tan, Hon Liang; Yap, John Q; Qian, Qi

    2016-01-01

    Acute kidney injury (AKI) is a common clinical syndrome directly related to patient short-term and long-term morbidity and mortality. Over the last decade, the occurrence rate of AKI has been increasing, and there has also been a growing epidemic of chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) linked to severe and repeated episodes of AKIs. The detection and management of AKI are currently far from satisfactory. A large proportion of AKI patients, especially those with preexisting CKD, are at an increased risk of non-resolving AKI and progressing to CKD and ESRD. Proposed pathological processes that contribute to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, alterations of tubular cell phenotype with cells predominantly in the G2/M phase, interstitial fibrosis and microvascular rarification related to loss of endothelial-pericyte interactions and pericyte dedifferentiation. Innate immune responses, especially dendritic cell responses related to inadequate adenosine receptor (2a)-mediated signals, autophagic insufficiency and renin-angiotensin system activation have also been implicated in the progression of AKI and transitions from AKI to CKD and ESRD. Although promising advances have been made in understanding the pathophysiology of AKI and AKI consequences, much more work needs to be done in developing biomarkers for detecting early kidney injury, prognosticating kidney disease progression and developing strategies to effectively treat AKI and to minimize AKI progression to CKD and ESRD.

  9. BMP-7 Signaling and its Critical Roles in Kidney Development, the Responses to Renal Injury, and Chronic Kidney Disease.

    Science.gov (United States)

    Manson, Scott R; Austin, Paul F; Guo, Qiusha; Moore, Katelynn H

    2015-01-01

    Chronic kidney disease (CKD) is a significant health problem that most commonly results from congenital abnormalities in children and chronic renal injury in adults. The therapeutic potential of BMP-7 was first recognized nearly two decades ago with studies demonstrating its requirement for kidney development and ability to inhibit the pathogenesis of renal injury in models of CKD. Since this time, our understanding of CKD has advanced considerably and treatment strategies have evolved with the identification of many additional signaling pathways, cell types, and pathologic processes that contribute to disease progression. The purpose of this review is to revisit the seminal studies that initially established the importance of BMP-7, highlight recent advances in BMP-7 research, and then integrate this knowledge with current research paradigms. We will provide an overview of the evolutionarily conserved roles of BMP proteins and the features that allow BMP signaling pathways to function as critical signaling nodes for controlling biological processes, including those related to CKD. We will discuss the multifaceted functions of BMP-7 during kidney development and the potential for alterations in BMP-7 signaling to result in congenital abnormalities and pediatric kidney disease. We will summarize the renal protective effects of recombinant BMP-7 in experimental models of CKD and then propose a model to describe the potential physiological role of endogenous BMP-7 in the innate repair mechanisms of the kidneys that respond to renal injury. Finally, we will highlight emerging clinical approaches for applying our knowledge of BMP-7 toward improving the treatment of patients with CKD.

  10. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Directory of Open Access Journals (Sweden)

    Dhananjay R Namjoshi

    Full Text Available Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE, a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS. How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  11. The effects of chronic radiation on reproductive success of the polychaete worm Neanthes arenaceodentata

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, F.L.; Anderson, S.L.

    1988-12-01

    The effects of lifetime exposure to chronic irradiation on reproductive success were assessed for laboratory populations of the polychaete worm Neanthes arenaceodentata. Lifetime exposure was initiated upon the spawning of the P1 female and was terminated upon spawning of the F1 female. Groups of experimental worms received either no radiation (controls) or 0.19, 2.1, or 17 mGy/h. The total dose received by the worms was either background or approximately 0.55, 6.5, or 54 Gy, respectively. The broods from the F1 mated pairs were sacrificed before hatching occurred, and information was obtained on brood size, on the number of normal and abnormal embryos, and on the number of embryos that were living, dying, and dead. The mean number of embryos in the broods from the F1 females exposed to lifetime radiation of 0.19 and 2.1 mGy/h was not significantly different from the mean number of embryos from control females; however, the mean number of embryos was different from those F1 females exposed to 17 mGy/h. There was a significant reduction in the number of live embryos in the broods from the F1 mated pairs that were exposed to the lowest dose rate given, 0.19 mGy/h, as well as those exposed to 2.1 and 17 mGy/h. Also, increased percentages of abnormal embryos were determined in the broods of all the radiation-exposed groups. 39 refs., 10 figs., 15 tabs.

  12. Clinical specificity of acute versus chronic self-injury: measurement and evaluation of repetitive non-suicidal self-injury.

    Science.gov (United States)

    Manca, Maura; Presaghi, Fabio; Cerutti, Rita

    2014-01-30

    Overall, previous studies on the prevalence of non-suicidal self-injury (NSSI) behaviors in the general population have stressed the importance of differentiating between occasional and repetitive NSSI, examining different severity levels (e.g., frequency and variety of methods), as well as investigating the diverse psychopathological correlates of NSSI. However, existing NSSI measures have not been explicitly developed by to comply with the NSSI diagnostic criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The purpose of this study is to develop a measure of repetitive NSSI by considering its essential features, as described in the proposed DSM-5 as well as in other clinically relevant aspects emerging from case reports. Two independent samples of participants (N1=383 young adults and 251 adolescents; N2=953 adolescents) belonging to the general population were involved in the present study. The questionnaire showed satisfactory fit statistics and reliably discriminated between occasional and repetitive self-injurers (Area Under Curve, AUC=0.755). The pattern of correlations with psychopathological measures confirmed a more clinically-compromised profile for repetitive rather than occasional self-injurers.

  13. [Radiation situation prognosis for deep space: reactions of water and living systems to chronic low-dose ionizing irradiation].

    Science.gov (United States)

    Ushakov, I B; Tsetlin, V V; Moisa, S S

    2013-01-01

    The authors review the findings of researches into the effects of low-dose ionizing irradiation on diverse biological objects (embryonic Japanese quails, Aspergillus niger, Spirostomum ambiguum Ehrbg., mesenchymal stem cells from mouse marrow, dry higher plants seeds, blood lymphocytes from pilots and cosmonauts). Model experiments with chronic exposure to ionizing radiation doses comparable with the measurements inside orbital vehicles and estimations for trips through the interplanetary space resulted in morphological disorders (embryonic Japanese quails, Aspergillus niger), radiation hormesis (Aspergillus niger, MSCs from mouse marrow), increase in the seed germination rate, inhibition of Spirostomum spontaneous activity, DNA damages, chromosomal aberrations, and increase of the blood lymphocytes reactivity to additional radiation loading. These facts give grounds to assume that the crucial factor in the radiation outcomes is changes in liquid medium. In other words, during extended orbiting within the magnetosphere region and interplanetary missions ionizing radiation affects primarily liquids of organism and, secondarily, its morphofunctional structures.

  14. A novel cardioprotective agent in cardiac transplantation: metformin activation of AMP-activated protein kinase decreases acute ischemia-reperfusion injury and chronic rejection.

    Science.gov (United States)

    Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P

    2011-12-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.

  15. Effects of chronic ethanol administration on expression of BDNF and trkB mRNAs in rat hippocampus after experimental brain injury.

    Science.gov (United States)

    Zhang, L; Dhillon, H S; Barron, S; Hicks1, R R; Prasad, R M; Seroogy, K B

    2000-06-23

    Previous evidence indicates that both chronic alcohol treatment and traumatic brain injury modulate expression of certain neurotrophins and neurotrophin receptors in cortical tissue. However, the combined effects of chronic alcohol and brain trauma on expression of neurotrophins and their receptors have not been investigated. In the present study, we examined the effects of 6 weeks of chronic ethanol administration on lateral fluid percussion (FP) brain injury-induced alterations in expression of mRNAs for the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor, trkB, in rat hippocampus. In both the control- (pair-fed isocaloric sucrose) diet and the chronic ethanol-diet groups, unilateral FP brain injury induced a bilateral increase in levels of both BDNF and trkB mRNAs in the dentate gyrus granule cell layer, and of BDNF mRNA in hippocampal region CA3. However, no significant differences in expression were found between the control-diet and ethanol-diet groups, in either the sham-injured or FP-injured animals. These findings suggest that 6 weeks of chronic ethanol administration does not alter the plasticity of hippocampal BDNF/trkB expression in response to experimental brain injury.

  16. Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation. [Paramecium tetraurelia; Synechococcus lividus

    Energy Technology Data Exchange (ETDEWEB)

    Planel, H.; Soleilhavoup, J.P.; Tixador, R.; Richoilley, G.; Conter, A.; Croute, F.; Caratero, C.; Gaubin, Y.

    1987-05-01

    Investigations carried out on the protozoan Paramecium tetraurelia and the cyanobacteria Synechococcus lividus, which were shielded against background radiation or exposed to very low doses of gamma radiation, demonstrated that radiation can stimulate the proliferation of these two single-cell organisms. Radiation hormesis depends on internal factors (age of starting cells) and external factors (lighting conditions). The stimulatory effect occurred only in a limited range of doses and disappeared for dose rates higher than 50 mGy/y.

  17. An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

    Directory of Open Access Journals (Sweden)

    Xiang-Ming Fang

    2015-01-01

    Full Text Available Background: To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury (RILI for the future investigation of computed tomography perfusion. Methods: A total of 72 New Zealand rabbits were randomly divided into two groups: 36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung; 36 rabbits in the control group were sham-radiated. All rabbits were subsequently sacrificed at 1, 6, 12, 24, 48, 72 h, and 1, 2, 4, 8,1 6, 24 weeks after radiation, and then six specimens were extracted from the upper, middle and lower fields of the bilateral lungs. The pathological changes in these specimens were observed with light and electron microscopy; the expression of tumor necrosis factor-α (TNF-a and transforming growth factor-β1 (TGF-β1 in local lung tissue was detected by immunohistochemistry. Results: (1 Radiation-induced lung injury occurred in all rabbits in the test group. (2 Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation, demonstrated a statistically significant difference between the test and control groups (each P 0.05. At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups (each P < 0.05, correlating well with the time postradiation (r = 0.99318. Conclusions: A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray, which can simulate the development and evolution of RILI.

  18. Acute ischemia/reperfusion injury after isogeneic kidney transplantation is mitigated in a rat model of chronic renal failure.

    Science.gov (United States)

    Vercauteren, Sven R; Ysebaert, Dirk K; Van Rompay, An R; De Greef, Kathleen E; De Broe, Marc E

    2003-05-01

    The influence of chronic renal failure on renal susceptibility to an acute ischemic insult was evaluated. Recipient Lewis rats were randomly assigned to undergo 5/6 nephrectomy (chronic renal failure, CRF) or sham operation (normal renal function, NRF). After 11 weeks, normal kidneys of Lewis donor rats were transplanted in the recipients. The outcome of the isografts was assessed. Filtration capacity of the isografts in the CRF rats was preserved to approximately one-quarter of its normal capacity on the 1st day post-transplantation, whereas it fell to 0 in the NRF rats. This was reflected by a significantly higher increase in serum creatinine in the latter group. The isografts in the CRF rats had a significantly lower degree of acute tubular necrosis and no increase in the number of macrophages and T lymphocytes in the first 24 h in contrast to the NRF rats. Epithelial regeneration and repair started earlier in the CRF group. In conclusion, the present study indicated that CRF blunted ischemia/reperfusion injury of a transplanted kidney, and that its regeneration capacity was certainly not hampered by the presence of chronic uremia. These results will be the basis for studies on modulation of early leukocyte-endothelial interactions resulting from immunological disturbances inherent to the uremic environment.

  19. [Reactive anxiety crisis and chronic adjustment disorder: a unique case of work injury and suspected occupational disease].

    Science.gov (United States)

    Taino, Giuseppe; Pizzuto, Cristina; Pezzuto, Cristina; Pucci, Ennio; Imbriani, Marcello

    2014-01-01

    The present study aims to describe a case of work injury and occupational disease which is unique for the type of disease diagnosed, conditions of onset and mode of management by INAIL (Italian National Institute of Insurance for Injuries at Work and Occupational Diseases). A worker, after a verbal animated dispute with some collegues and superiors, had an acute psychiatric agitation attack and went to the nearest emergency room, where he was subjected to clinical exams. No neuropsychiatric alteration was found, but the physicians diagnosed an anxiety crisis reactive to the work environment. Consequently, the medical certificate for work injury was edited and sent to INAIL. The worker has been off work for 110 days because of a anxious and depressive syndrome, due to the verbal conflict. In a later assessment, INAIL recognized only the first 30 days of the employee's time off as injury at work, while judging the following period off work as related to affectivity disturbance due to common disease, not related to work environment. The following year, "anxious-depressive syndrome" is worsened and attributed by the same worker to the recurrence of acts of persecution and discrimination against him at work. For this reason he applied for recognition of occupational disease diagnosed as "Chronic Adjustment Disorder with prolonged depressive reaction and somatic anxiety, which developed into a protracted conflict marked the employment situation". INAIL rejected that request, but in the same year the employee has submitted the complaint for "mobbing". Even this request was rejected. Literature shows many examples of traumatic events during working activities which cause psychiatric disturbances. These events include industrial disasters, explosions, transport and mining accidents, accidents in psychiatric units with high risks of assaults, armed conflicts, war, assault and sexual assault, natural disasters. Victims show symptoms of acute stress disorder (ASD) or post

  20. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

    Science.gov (United States)

    2015-07-01

    DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response...reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including...chronic neuronal cell loss, glial activation, and chronic traumatic encephalopathy (CTE) measure of β-amyloid and hyper-phosphorylated tau protein

  1. Do X-ray-occult fractures play a role in chronic pain following a whiplash injury?

    DEFF Research Database (Denmark)

    Hertzum-Larsen, Rasmus; Petersen, Henrik; Kasch, Helge

    2014-01-01

    symptoms following an MVA was invited to have a cervical SPECT shortly post injury and again 6 months later. Associations between occult fractures and pain levels at baseline, 6 and 12 months of follow-up were analyzed. Eighty-eight patients had baseline SPECT performed at median 15 days (range 3-28) post...... injury, but only 49 patients accepted to have the follow-up SPECT at 6 months. Abnormal SPECT, defined as minimum one area of focal uptake, was seen in 32 patients at baseline, reflecting an occult fracture. Occult fractures were not associated with pain levels, neither at baseline nor at follow...

  2. Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

    Science.gov (United States)

    Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

    2016-06-01

    Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length.

  3. Depression, anxiety and quality of life in caregiver spouses of veterans with chronic spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Mohammad Hosein Ebrahimzadeh

    2014-09-01

    Full Text Available We were curious about the degree of anxiety and depression and their effect on the quality of life of the caregivers of veterans with spinal cord injury (SCI.A convenience sample of 72 out of 120 caregiver spouses of veterans with spinal cord injury participated in our study. The Hospital Anxiety and Depression Scale (HADS were considered as a measure of depression and anxiety. The World Health Organization Quality of Life BREF questionnaire (WHOQOL-BREF was considered to evaluate the quality of life. To compare the caregivers, we enrolled 74 matched caregiver spouses of patients without spinal cord injury.The average age of the spouses was 44.7±6.5. The average time elapsed from the injury was 26.4±3.1 years. There was a significant difference in all domains of quality of life and depression between the caregivers and the control group, but there was not a significant difference in terms of anxiety. There was a negative correlation between depression and age, level of education and quality of life.Mental care support should be implemented for veterans and their spouses in addition to the provided facilities.

  4. Cognitive behavioural treatment programme for chronic neuropathic pain after spinal cord injury

    NARCIS (Netherlands)

    Heutink, M.

    2014-01-01

    People with spinal cord injury (SCI) often face serious secondary health conditions, including different types of pain. Neuropathic pain is often rated by them as the most severe type of pain. Pharmacological interventions are often insufficiently effective in providing neuropathic pain relief and,

  5. Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury : Acute versus chronic disturbances?

    NARCIS (Netherlands)

    Metting, Zwany; Spikman, Jacoba M.; Rodiger, Lars A.; van der Naalt, Joukje

    2014-01-01

    In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully unde

  6. Effects of chronic restraint-induced stress on radiation-induced chromosomal aberrations in mouse splenocytes.

    Science.gov (United States)

    Katsube, Takanori; Wang, Bing; Tanaka, Kaoru; Ninomiya, Yasuharu; Varès, Guillaume; Kawagoshi, Taiki; Shiomi, Naoko; Kubota, Yoshihisa; Liu, Qiang; Morita, Akinori; Nakajima, Tetsuo; Nenoi, Mitsuru

    2017-01-01

    Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53(+/-)) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53(+/+)) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53(+/+) C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR.

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

    Science.gov (United States)

    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.

  8. Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response

    Institute of Scientific and Technical Information of China (English)

    Jacqueline JCM Kruse; Fiona A Stewart

    2007-01-01

    Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research. The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PubMed literature search was conducted using the following keywords and combination of terms: radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways: (1) to generate gene signatures to identify sensitive and resistant populations (prognosis); (2) to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack (diagnosis); (3) to identify genes and pathways involved in tissue response to injury (mechanistic). In this article we will review all (relevant) papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

  9. An educational approach based on a non-injury model compared with individual symptom-based physical training in chronic LBP

    DEFF Research Database (Denmark)

    Sorensen, Pia H; Bendix, Tom; Manniche, Claus

    2010-01-01

    In the treatment of chronic back pain, cognitive methods are attracting increased attention due to evidence of effectiveness similar to that of traditional therapies. The purpose of this study was to compare the effectiveness of performing a cognitive intervention based on a non-injury model with...

  10. Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis

    Science.gov (United States)

    Elvington, M; Schepp-Berglind, J; Tomlinson, S

    2015-01-01

    The role of complement in inflammatory bowel disease (IBD) has been studied primarily using acute models, and it is unclear how complement affects processes in more relevant chronic models of IBD in which modulation of adaptive immunity and development of fibrosis have pathogenic roles. Using mice deficient in C1q/mannose-binding lectin (MBL) or C3, we demonstrated an important role for these opsonins and/or the classical pathway C3 convertase in providing protection against mucosal injury and infection in a model of chronic dextran sulphate sodium (DSS)-induced colitis. In contrast, deficiency of the alternative pathway (fB–/– mice) had significantly less impact on injury profiles. Consequently, the effect of a targeted inhibitor of the alternative pathway was investigated in a therapeutic protocol. Following the establishment of colitis, mice were treated with CR2-fH during subsequent periods of DSS treatment and acute injury (modelling relapse). CR2-fH significantly reduced complement activation, inflammation and injury in the colon, and additionally reduced fibrosis. Alternative pathway inhibition also altered the immune response in the chronic state in terms of reducing numbers of B cells, macrophages and mature dendritic cells in the lamina propria. This study indicates an important role for the alternative pathway of complement in the pathogenesis and the shaping of an immune response in chronic DSS-induced colitis, and supports further investigation into the use of targeted alternative pathway inhibition for the treatment of IBD. PMID:25293413

  11. Prospective study of a community reintegration programme for patients with acquired chronic brain injury: effects on caregivers' emotional burden and family functioning

    NARCIS (Netherlands)

    Geurtsen, G.J.; Heugten, C.M. van; Meijer, R.; Martina, J.D.; Geurts, A.C.H.

    2011-01-01

    Objective: To examine the effects of a residential community reintegration programme for patients with psychosocial problems due to acquired chronic brain injury on caregivers' emotional burden and family functioning. Design: A prospective cohort study with waiting list control and 1-year follow-up.

  12. Occupational chronic muscle and bone injury%职业性慢性肌肉骨骼损伤

    Institute of Scientific and Technical Information of China (English)

    张坤海; 赵欣

    2002-01-01

    @@ 因工作引起的慢性肌肉骨骼损伤(chronic musculo-skeletal injury,CMI)是一种常见的职业性多发病,目前在一些国家已成为主要的职业健康问题,欧美等国将其列入职业病范畴,也引起国内学者的广泛关注.根据目前国内外的研究状况和趋势,本文结合有关文献,对有关职业性慢性肌肉骨骼损伤研究进展作一综述.

  13. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S. [Russian Inst. of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2000-05-01

    The analysis undertaken by us of the experimentally observed cellular responses to low dose irradiation has shown that the relationship between the yield of induced cytogenetic damage and radiation dose within low dose range is non-linear and universal in character. Because of the relationship between the yield of cytogenetic damage and dose within low dose range is non-linear, the aberration frequency cannot be used in biological dosimetry in the most important in terms of practical application case. The cytogenetic damage frequency cannot be used in biological dosimetry also because of the probability of synergistic and antagonistic interaction effects of the different nature factors simultaneously acting on test-object in real conditions is high within low dose (concentration) range. In our experimental study of the regularities in the yield of structural mutations in conditions of combined influence of ionizing radiation, heavy metals and pesticides it was found that synergistic and antagonistic effects are mainly induced in conditions of combined action of low exposure injuring agents. Experiments on agricultural plants were carried out in 1986-1989 at the 30-km zone around Chernobyl NPP. It was shown that chronic low dose exposure could cause an inheritable destabilization of genetic structures expressing in increase of cytogenetic damage and yield karyotypic variability in offspring's of irradiated organisms. Obviously exactly this circumstance is the reason of the phenomenon found in our researches of significant time delay of cytogenetic damage reduction rate from radioactive pollution reduction rate from time past from the accident moment. Research of cytogenetic damage of reproductive (seeds) and vegetative (needles) plant organs of the Pinus sylvestris tree micropopulations growing in contrast by radioactive pollution level sites of the 30-km ChNPP zone and also in the vicinity of the industrial plant <> for processing and temporary storage

  14. T1-mapping for assessment of ischemia-induced acute kidney injury and prediction of chronic kidney disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hueper, Katja; Gutberlet, Marcel; Wacker, Frank; Hartung, Dagmar [Hannover Medical School, Department of Radiology, Hannover (Germany); Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Peperhove, Matti; Tewes, Susanne; Barrmeyer, Amelie [Hannover Medical School, Department of Radiology, Hannover (Germany); Rong, Song [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zunyi Medical College, Laboratory of Organ Transplantation, Zunyi (China); Gerstenberg, Jessica; Haller, Herman; Gueler, Faikah [Hannover Medical School, Department of Nephrology, Hannover (Germany); Mengel, Michael [University of Alberta, Department of Laboratory Medicine and Pathology, Edmonton (Canada); Meier, Martin [Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Hannover Medical School, Institute for Animal Science, Hannover (Germany); Chen, Rongjun [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zhejiang University, The Kidney Disease Center of the First Affiliated Hospital, Hangzhou (China)

    2014-09-15

    To investigate whether T1-mapping allows assessment of acute kidney injury (AKI) and prediction of chronic kidney disease (CKD) in mice. AKI was induced in C57Bl/6N mice by clamping of the right renal pedicle for 35 min (moderate AKI, n = 26) or 45 min (severe AKI, n = 23). Sham animals served as controls (n = 9). Renal histology was assessed in the acute (day 1 + day 7; d1 + d7) and chronic phase (d28) after AKI. Furthermore, longitudinal MRI-examinations (prior to until d28 after surgery) were performed using a 7-Tesla magnet. T1-maps were calculated from a fat-saturated echoplanar inversion recovery sequence, and mean and relative T1-relaxation times were determined. Renal histology showed severe tubular injury at d1 + d7 in both AKI groups, whereas, at d28, only animals with prolonged 45-min ischemia showed persistent signs of AKI. Following both AKI severities T1-values significantly increased and peaked at d7. T1-times in the contralateral kidney without AKI remained stable. At d7 relative T1-values in the outer stripe of the outer medulla were significantly higher after severe than after moderate AKI (138 ± 2 % vs. 121 ± 3 %, p = 0.001). T1-elevation persisted until d28 only after severe AKI. Already at d7 T1 in the outer stripe of the outer medulla correlated with kidney volume loss indicating CKD (r = 0.83). T1-mapping non-invasively detects AKI severity in mice and predicts further outcome. (orig.)

  15. Feasibility of Human Amniotic Fluid Derived Stem Cells in Alleviation of Neuropathic Pain in Chronic Constrictive Injury Nerve Model.

    Directory of Open Access Journals (Sweden)

    Chien-Yi Chiang

    Full Text Available The neurobehavior of neuropathic pain by chronic constriction injury (CCI of sciatic nerve is very similar to that in humans, and it is accompanied by a profound local inflammation response. In this study, we assess the potentiality of human amniotic fluid derived mesenchymal stem cells (hAFMSCs for alleviating the neuropathic pain in a chronic constriction nerve injury model.This neuropathic pain animal model was conducted by four 3-0 chromic gut ligatures loosely ligated around the left sciatic nerve in Sprague-Dawley rats. The intravenous administration of hAFMSCs with 5x105 cells was conducted for three consecutive days.The expression IL-1β, TNF-α and synaptophysin in dorsal root ganglion cell culture was remarkably attenuated when co-cultured with hAFMSCs. The significant decrease of PGP 9.5 in the skin after CCI was restored by administration of hAFMSCs. Remarkably increased expression of CD 68 and TNF-α and decreased S-100 and neurofilament expression in injured nerve were rescued by hAFMSCs administration. Increases in synaptophysin and TNF-α over the dorsal root ganglion were attenuated by hAFMSCs. Significant expression of TNF-α and OX-42 over the dorsal spinal cord was substantially attenuated by hAFMSCs. The increased amplitude of sensory evoked potential as well as expression of synaptophysin and TNF-α expression was alleviated by hAFMSCs. Human AFMSCs significantly improved the threshold of mechanical allodynia and thermal hyperalgesia as well as various parameters of CatWalk XT gait analysis.Human AFMSCs administration could alleviate the neuropathic pain demonstrated in histomorphological alteration and neurobehavior possibly through the modulation of the inflammatory response.

  16. An herbal formula, CGX, exerts hepatotherapeutic effects on dimethylnitrosamine-induced chronic liver injury model in rats

    Institute of Scientific and Technical Information of China (English)

    Jang-Woo Shin; Myong-Min Lee; Xiao Ping Hu; Chang-Gue Son; Jin-Young Son; Se-Mi Oh; Seung-Hyun Han; Jing-Hua Wang; Jung-Hyo Cho; Chong-Kwan Cho; Hwa-Seung Yoo; Yeon-Weol Lee

    2006-01-01

    AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats.METHODS: Liver injuries were induced in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days per week for 4 wk. The rats were administered with CGX (po, 100 or 200 mg/kg per day) or distilled water as a control daily for 4 wk starting from the 15th d of the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and ALT), lipid peroxides,hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-α, TGF-β, TIMP-1, TIMP-2, PDGF-β, and MMP-2, all of which are known to be associated with liver fibrosis,were analyzed using real-time PCR.RESULTS: CGX administration restored the spleen weight to normal after having been increased by DMN treatment.Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP (P< 0.05), ALT (P < 0.01), and AST (P < 0.01) that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly upregulated expression of TNF-α, TGF-β, TIMP-1, TIMP-2,PDGF-β, and MMP-2. Of these, the gene expression encoding PDGF-β and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration.CONCLUSION: CGX exhibits hepatotherapeutic properties against chronic hepatocellular destruction and consequential liver fibrosis.

  17. An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

    Institute of Scientific and Technical Information of China (English)

    Xiang-Ming Fang; Chun-Hong Hu; Xiao-Yun Hu; Xuan-Jun Yao; Ping-Yan Qian; Ju-Ying Zhou; Jian Guo

    2015-01-01

    Background:To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury (RILI) for the future investigation of computed tomography perfusion.Methods:A total of 72 New Zealand rabbits were randomly divided into two groups:36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were sham-radiated.All rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral lungs.The pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α (TNF-a) and transforming growth factor-βl (TGF-β1) in local lung tissue was detected by immunohistochemistry.Results:(1) Radiation-induced lung injury occurred in all rabbits in the test group.(2) Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups (each P < 0.05).(3) Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters (each P < 0.05):thickness of alveolar wall,density of pulmonary interstitium area (1 h after radiation),number offibroblasts and fibrocytes in interstitium (24 h after radiation).The test group metrics also correlated well with the time ofpostradiation.(4) Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group (P < 0.005),with no significant differences in the control group (P > 0.05).At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups (each P < 0.05),correlating well with the time postradiation (r =0

  18. [Relationships between low-grade chronic depression, pain and personality traits among community-dwelling persons with traumatic spinal cord injury].

    Science.gov (United States)

    Nagumo, N

    2000-08-01

    To examine the relationships between low-grade chronic depression, pain and personality traits among community-dwelling persons with traumatic spinal cord injury (TSCI), 111 male and 11 female TSCI persons were administered questionnaires including Self-rating Depression Scale (SDS) and measures of pain and other mental health items, and were followed-up two years later. Nineteen persons (15%) meeting the criteria for low-grade chronic depression (both SDS scores > or = 48) were identified, while 30% of the sample population consistently showed normal mood (both SDS scores pain and B type (emotionally labile, socially maladjusted, and extraverted personality characteristic) associated with lower IQ (90 and less) were significantly related to high SDS scores. However, age, sex, time-since-injury, levels of injury and marital status had no relationship with depression.

  19. Effects of chronic exposure to ionising radiation in the Pacific oyster Crassostrea gigas

    Energy Technology Data Exchange (ETDEWEB)

    Fievet, B.; Devos, A.; Voiseux, C.; Leconte-Pradines, C. [Institut de Radioprotection et de Surete' Nucleaire (France); Dallas, L.; Jha, A. [University of Plymouth (United Kingdom)

    2014-07-01

    The Cotentin peninsula (Normandy, France) hosts nuclear industry facilities which operate with controlled discharges of radionuclides in the marine environment. Compared to natural radioactivity, the increase by artificial radionuclides is small but constant. As a consequence, marine species are chronically exposed to low additional doses of ionizing radiation (IR). The effects of chronic exposure to radionuclides were investigated in early stages of development of the Japanese oyster Crassostrea gigas. On the basis of literature, mollusks are expected to be particularly resistant to acute IR (UNSCEAR, 1996. Sources and effects of ionizing radiation. Report to the General Assembly, with Scientific Annex. 86 p). Two different chronic exposure conditions consisted in external ({sup 137}Cs) and internal ({sup 241}Am) irradiation for two weeks. Biological endpoints were analyzed in parallel at both the integrated (growth) and molecular (target stress gene expression) levels. To identify potential biological targets of IR, oysters were first exposed to very high dose rates and radionuclide activities with the perspective to reduce the levels and to derive dose-response curves. Although the initial exposure levels ({sup 137}Cs 30 000 μGy.h{sup -1}; {sup 241}Am 57 000 Bq.L{sup -1}) were many orders of magnitude higher than those encountered in the natural environment, no significant change in the measured parameters was observed. This result was surprising because data from the literature showed that exposure of mussel Mytilus edulis to {sup 3}H at lower doses rates (10-100 μGy.h{sup -1}) induced DNA damage in hemocytes (Jha et al., 2005. Impact of low doses of tritium on the marine mussel, Mytilus edulis: Genotoxic effects and tissue-specific bioconcentration. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 586, 47-57). To understand this apparent discrepancy between those two filtering bivalves, a new experiment was performed to compare the response

  20. Pilot study: Computer-based virtual anatomical interactivity for rehabilitation of individuals with chronic acquired brain injury.

    Science.gov (United States)

    Simmons, C Douglas; Arthanat, Sajay; Macri, Vincent J

    2014-01-01

    Deficiencies in upper-limb motor function and executive functioning can compromise an affected individual's ability to complete everyday activities. Impaired motor and executive functioning therefore pose a risk to increasing numbers of veterans who have been diagnosed with acquired brain injury. This article reports on changes in upper-limb motor function and executive functioning of 12 adult participants with chronic acquired brain injury using a novel, computer-based, motor and cognitive rehabilitation program called PreMotor Exercise Games (PEGs). Manual muscle, goniometric range of motion, and dynamometer assessments were used to determine motor functioning while the Executive Function Performance Test measured cognitive functioning. A three-level repeated measures design was conducted to determine changes pre- and postintervention. Participants demonstrated significant improvement in shoulder (p = 0.01) and wrist (p = 0.01) range of motion and clinically relevant improvement for elbow range of motion. Participants demonstrated clinically relevant improvement in shoulder, elbow, and wrist strength. Finally, participants demonstrated significant improvement in executive functioning (p rehabilitation and warrants further study.

  1. Does Environmental Enrichment Exposure Prior to Injury Influence Biomarkers Associated with Chronic Stage TBI?

    Science.gov (United States)

    2012-12-01

    subjected to TBI via a controlled cortical impact (CCI) device. Animals were anesthetized with isoflurane (5% induction , 2% maintenance) and...BDNF mRNA expression in the rat hippocampus after traumatic brain injury. Molecular Neuroscience. 11(15): 3381-3384 Hamm, R.J., Temple , M.D...Factors. RR Donnelly Willard. Pg. 96-99 Marmigere, F., Givalois, L., Rage, F., Arancibia, S., Tapia-Arancibia, L. (2003). Rapid induction of

  2. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

    Directory of Open Access Journals (Sweden)

    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  3. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

    Science.gov (United States)

    Le Clef, Nathalie; Verhulst, Anja; D'Haese, Patrick C; Vervaet, Benjamin A

    2016-01-01

    Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis) is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care) with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  4. Acute-on-chronic kideny injury in hospitalized patients:a clinical survey

    Institute of Scientific and Technical Information of China (English)

    王琴

    2013-01-01

    Objective To investigate the incidence and risk factors of acute-on-chronic kidney(A-on-C) in hospitalized patients. Methods We did a retrospective study on the clinical profiles of patients with A-on-C hospitalized in Affiliated Renji Hospital of Shanghai Jiaotong University

  5. Collateral ligament reconstruction of the chronic thumb injury with bio-tenodesis screw fixation

    DEFF Research Database (Denmark)

    Gvozdenovic, Robert; Boeckstyns, Michel

    2014-01-01

    We describe a new technique for the reconstruction of chronic lesions of the collateral ligaments of the metacarpophalangeal ligaments of the thumb, using a Bio-Tenodesis screw for the fixation of a tendon graft in a triangular manner with proximal apex and allowing early mobilization, starting 2...

  6. Elevated serum titers of proinflammatory cytokines and CNS autoantibodies in patients with chronic spinal cord injury.

    Science.gov (United States)

    Hayes, K C; Hull, T C L; Delaney, G A; Potter, P J; Sequeira, K A J; Campbell, K; Popovich, P G

    2002-06-01

    This study characterized the proinflammatory cytokines, interleukin-2 (IL-2) and tumor necrosis factor alpha (TNFalpha), the antiinflammatory cytokines, IL-4 and IL-10, autoantibodies specific for GM1 ganglioside (anti-GM1), IgG and IgM, and myelin-associated glycoprotein (anti-MAG), in the sera of infection-free, chronic (>12 months), traumatically injured SCI patients (n = 24). Healthy able-bodied subjects (n = 26) served as controls. The proinflammatory cytokines and anti-GM1 antibodies were of particular interest as they have been implicated in an autoimmune "channelopathy" component to central and peripheral conduction deficits in various chronic neuroinflammatory diseases. Antibody and cytokine titers were established using enzyme-linked immunosorbent assays (ELISA). The mean anti-GM(1) (IgM) titer value for the SCI group was significantly higher (p proinflammatory cytokines relative to control values. These results provide preliminary support for the hypothesis that chronic immunological activation in the periphery occurs in a subpopulation of chronic SCI patients. It remains to be established whether elevated serum titers of proinflammatory cytokines and autoantibodies against GM1 are beneficial to the patients or whether they are surrogate markers of a channelopathy that compounds the neurological impairment associated with traumatic axonopathy or myelinopathy.

  7. Leptin is essential for the hepatic fibrogenic response to chronic liver injury

    NARCIS (Netherlands)

    Leclercq, IA; Farrell, GC; Schriemer, R; Robertson, GR

    2002-01-01

    Background/Aims: Obesity is associated with hyperleptinemia and is also a risk factor for fibrosis and severity of fibrosis in several chronic liver diseases. The correlation between increased leptin, obesity and hepatic fibrosis prompted us to hypothesise that leptin has profibrogenic effects on th

  8. Chronic Losartan Treatment Up-Regulates AT1R and Increases the Heart Vulnerability to Acute Onset of Ischemia and Reperfusion Injury in Male Rats.

    Science.gov (United States)

    Song, Minwoo A; Dasgupta, Chiranjib; Zhang, Lubo

    2015-01-01

    Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.

  9. Ionizing radiation exposures in treatments of solid neoplasms are not associated with subsequent increased risks of chronic lymphocytic leukemia.

    Science.gov (United States)

    Radivoyevitch, Tomas; Sachs, Rainer K; Gale, Robert Peter; Smith, Mitchell R; Hill, Brian T

    2016-04-01

    Exposure to ionizing radiation is not thought to cause chronic lymphocytic leukemia (CLL). Challenging this notion are recent data suggesting CLL incidence may be increased by radiation exposure from the atomic bombs (after many decades), uranium mining and nuclear power facility accidents. To assess the effects of therapeutic ionizing radiation for the treatment of solid neoplasms we studied CLL risks in data from the Surveillance, Epidemiology, and End Results (SEER) Program. Specifically, we compared the risks of developing CLL in persons with a 1(st) non-hematologic cancer treated with or without ionizing radiation. We controlled for early detection effects on CLL risk induced by surveillance after 1(st) cancer diagnoses by forming all-time cumulative CLL relative risks (RR). We estimate such CLL RR to be 1.20 (95% confidence interval, 1.17, 1.23) for persons whose 1(st) cancer was not treated with ionizing radiation and 1.00 (0.96, 1.05) for persons whose 1(st) cancer was treated with ionizing radiations. These results imply that diagnosis of a solid neoplasm is associated with an increased risk of developing CLL only in persons whose 1(st) cancer was not treated with radiation therapy.

  10. Radiation safety protocol for high dose 131I therapy of thyroid carcinoma in patients on hemodialysis for chronic renal failure.

    Science.gov (United States)

    Modarresifar, Homayoun; Almodovar, Samuel; Bass, William B; Ojha, Buddhiwardhan

    2007-02-01

    Iodine ablation therapy for thyroid cancer on patients receiving dialysis poses unique radiation safety challenges. Exposure to gamma and beta negative particles by the hemodialysis (HD) staff is a concern that has not been well studied. A 53-y-old male patient on HD for chronic renal failure was scheduled for 131I high dose therapy as treatment for thyroid papillary carcinoma. The patient was on HD every other day, prior to ablation. A high dose of 131I (3,607.5 MBq) was required. The patient was admitted for 131I therapy, and continued HD. Thyroid cancer ablation therapy was administered according to our institutional protocol. New radiation safety measures were developed and implemented in order to give the patient an optimal treatment dose, reduce radiation to the patient (critical organs and whole body), and to protect the HD personnel. This included placing two lead shields between the patient and the HD nurse, and HD monitoring by two alternating nurses to reduce their radiation exposure. Film badges were used to measure radiation exposure to the nursing staff. Dosimetry calculations were obtained to determine radiation absorbed doses by the optic lens, skin, and whole body. Quality control verification for this shielding arrangement proved to be effective in protecting the HD staff against gamma and beta negative radiation from recent 131I high dose therapy. Implementation of this model proved to be an effective and adequate radiation safety protocol for limiting radiation exposure to the HD staff. The patient was given 3607.5 MBq for optimal treatment after HD. Hemodialysis was repeated after approximately 48 and 96 h to remove excess 131I and reduce radiation to the patient.

  11. Effect of delayed intrathecal administration of capsaicin on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats

    Directory of Open Access Journals (Sweden)

    Zhang K

    2014-09-01

    Full Text Available Kun Zhang,1 Somayaji Ramamurthy,1 Thomas J Prihoda,2 Maxim S Eckmann1 1Department of Anesthesiology, 2Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Purpose: The current study was designed to examine the antinociceptive effect of intrathecally administered capsaicin, a transient receptor potential vanilloid 1 receptor agonist, in a rat model of neuropathic pain induced by unilateral sciatic nerve chronic constriction injury. Methods: Male adult Sprague Dawley rats were randomly assigned to six groups, and all rats underwent unilateral sciatic nerve chronic constriction injury. Two weeks after injury, five groups received intrathecal administration of either capsaicin in three different dosing regimens or equal volumes of vehicle. The other group received intrathecal capsaicin on the third day after nerve injury. The antinociceptive effect of capsaicin was assessed by measuring the capsaicin-induced change in thermal and mechanical response thresholds. Results: Capsaicin (150–300 µg/100–200 µL, when administered by fast infusion or chronic infusions at 8 µL/hour or 1 µL/hour, attenuated thermal hyperalgesia as indicated by significantly prolonging paw withdrawal latency to noxious thermal stimulation. The antinociceptive effect of capsaicin was more profound in the injured limb compared to that in the uninjured limb. When capsaicin was administered on the third day after nerve injury, it failed to attenuate thermal hyperalgesia. No significant effect on the mechanical response threshold was observed with intrathecally administered capsaicin. Conclusion: Our data suggest that intrathecal capsaicin could significantly attenuate thermal hyperalgesia, depending on the time when the drug is given after nerve injury, and that the antinociceptive efficacy of intrathecal capsaicin positively correlates with the previously reported dynamic profile of spinal transient receptor potential

  12. Radial shock wave therapy in the treatment of chronic constriction injury model in rats: a preliminary study

    Institute of Scientific and Technical Information of China (English)

    Fu Miao; Cheng Hao; Li Duoyi; Yu Xiaotong; Ji Nan; Luo Fang

    2014-01-01

    Background Pain physicians pay close attention to neuropathic pain (NP),since there is currently no ideal treatment.Radial shock wave therapy (RSWT) is a noninvasive treatment to chronic pain of soft tissue disorders.So far,there is no information on the use of RSWT for the treatment of NP.Therefore we observe the effects of RSWT on a NP model induced by chronic constriction injury (CCI) in rats.Methods Four different energy densities (1.0,1.5,2.0 and 2.5 bar) RSWT administered as a single session or repeated sessions in rats with NP induced by CCI of the sciatic nerve.The analgesic effect was assessed by measuring mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL).The safety was assessed through calculating sciatic functional index (SFI).Results MWT and TWL increased after a single session of RSWT from day 1 to day 5 but retumed to baseline levels by day 10.Following repeated sessions of RSWT,both the MWT and TWL were significantly higher than NP group (P < 0.01)for at least 4 weeks.In addition,no significant changes of SFI were observed in any groups after repeated sessions of RSWT and no increased pain or other side effects in any animals.Conclusions A single session of RSWT is rapidly effective in the treatment of CCI,but the efficacy maintained in a short period.However,repeated sessions of RSWT have prolonged efficacy.

  13. Predictors of CNS Injury as Measured by Proton Magnetic Resonance Spectroscopy in the Setting of Chronic HIV infection and CART

    Science.gov (United States)

    Harezlak, J; Cohen, R; Gongvatana, A; Taylor, M; Buchthal, S; Schifitto, G; Zhong, J; Daar, ES; Alger, J; Brown, M; Singer, E; Campbell, TB; McMahon, D; So, YT; Yiannoutsos, CT; Navia, BA

    2014-01-01

    The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS) Metabolite concentrations (NAA/Cr, Cho/Cr, MI/Cr and Glx/Cr) were measured in the basal ganglia, the frontal white matter and grey matter and the best predictive models were selected using a bootstrap-enhanced Akaike Information Criterion (AIC). Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease. PMID:24696364

  14. Antiallodynic and antihyperalgesic effects of zerumbone on a mouse model of chronic constriction injury-induced neuropathic pain.

    Science.gov (United States)

    Zulazmi, Nurul Atiqah; Gopalsamy, Banulata; Farouk, Ahmad Akira Omar; Sulaiman, Mohd Roslan; Bharatham, B Hemabarathy; Perimal, Enoch Kumar

    2015-09-01

    Neuropathic pain is a chronic condition that is difficult to be treated. Current therapies available are either ineffective or non-specific thus requiring newer treatment approaches. In this study, we investigated the antiallodynic and antihyperalgesic effects of zerumbone, a bioactive sesquiterpene from Zingiber zerumbet in chronic constriction injury (CCI)-induced neuropathic pain animal model. Our findings showed that single and repeated dose of intra-peritoneal administration of zerumbone (5, 10, 50, 100 mg/kg) significantly attenuated the CCI-induced neuropathic pain when evaluated using the electronic von Frey anesthesiometer, cold plate, Randall-Selitto analgesiometer and the Hargreaves plantar test. Zerumbone significantly alleviated tactile and cold allodynia as well as mechanical and thermal hyperalgesia. Our findings are in comparison to the positive control drugs thatused gabapentin (20 mg/kgi.p.) and morphine (1 mg/kgi.p.). Together, these results showed that the systemic administration of zerumbone produced marked antiallodynic and antihyperalgesic effects in the CCI-induced neuropathic pain in mice and may serve as a potential lead compound for further analysis.

  15. [Morphological changes of peripheral nerve rats under chronic micromercurialism and its pharmacological correction in different terms after injury

    Directory of Open Access Journals (Sweden)

    Shamalо S.N.

    2015-09-01

    Full Text Available Background. Search for new pharmacological agents that activate processes of traumatized nerve regeneration at the condition of mercurial intoxication remains urgent. Objective. The aim of this study was a comparative morphometric analysis of rat peripheral nerve under micromercurialism using antioxidant drug without pharmacotherapy. Methods. Experimental model of sciatic nerve trauma under conditions of chronic micromercurialism was investigated in experiments on two groups of white rats. Micromercurialism was modeled by intraperitoneal injection of mercuric chloride during 10 weeks before sciatic nerve trauma. The rats of the first group received no pharmacological drugs in postoperative period. The second group of animals received 100 μg/kg solution of Thiotriazolinum intraperitoneally daily during 2 weeks after operation. The morphological organization and morphometric data of regenerative neuroma and adjoining parts (proximal and distal of sciatic nerve were studied in 6 and 12 weeks after damage using morphometric and statistic methods. Results. Basing on the results of the second group of animals the average angle of axon deviation from the axis of the nerve in the neuroma sufficiently decreases and distribution density of neuron fibers in distal part increases comparing with the first group. Conclusion. Taken together these data evidence that Thiotriazolinum improves the process of traumatized nerve regeneration. Citation: Shamalо SN. [Morphological changes of peripheral nerve rats under chronic micromercurialism and its pharmacological correction in different terms after injury]. Morphologia. 2015;9(3:95-8. Ukrainian.

  16. Optical coherence tomography and autofluorescence findings in chronic phototoxic maculopathy secondary to snow-reflected solar radiation

    Directory of Open Access Journals (Sweden)

    Dhananjay Shukla

    2015-01-01

    Full Text Available A professional mountain trekker presented with gradual, moderate visual decline in one eye. The subnormal vision could not be explained by the examination of anterior and posterior segment of either eye, which was unremarkable. Optical coherence tomography and autofluorescence imaging revealed subtle defects in the outer retina, which correlated with the extent of visual disturbance. A novel presentation of retinal phototoxicity due to indirect solar radiation reflected from snow in inadequately protected eyes of a chronically exposed subject is reported.

  17. Evaluating the effectiveness of reasoning training in military and civilian chronic traumatic brain injury patients: study protocol

    Directory of Open Access Journals (Sweden)

    Krawczyk Daniel C

    2013-01-01

    Full Text Available Abstract Background Individuals who sustain traumatic brain injuries (TBIs often continue to experience significant impairment of cognitive functions mediated by the prefrontal cortex well into chronic stages of recovery. Traditional brain training programs that focus on improving specific skills fall short of addressing integrative functions that draw upon multiple higher-order processes critical for social and vocational integration. In the current study, we compare the effects of two short-term, intensive, group-based cognitive rehabilitation programs for individuals with chronic TBI. One program emphasizes learning about brain functions and influences on cognition, while the other program adopts a top-down approach to improve abstract reasoning abilities that are largely reliant on the prefrontal cortex. These treatment programs are evaluated in civilian and military veteran TBI populations. Methods/design One hundred individuals are being enrolled in this double-blinded clinical trial (all measures and data analyses will be conducted by blinded raters and analysts. Each individual is randomly assigned to one of two treatment conditions, with each condition run in groups of five to seven individuals. The primary anticipated outcomes are improvement in abstract reasoning and everyday life functioning, measured through behavioral tasks and questionnaires, and attention modulation, as measured by functional neuroimaging. Secondary expected outcomes include improvements in the cognitive processes of working memory, attention, and inhibitory control. Discussion Results of this trial will determine whether cognitive rehabilitation aimed at teaching TBI-relevant information about the brain and cognition versus training in TBI-affected thinking abilities (e.g., memory, attention, and executive functioning can improve outcomes in chronic military and civilian TBI patient populations. It should shed light on the nature of improvements and the

  18. Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Yumin Xu

    Full Text Available BACKGROUND: Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF. METHODOLOGY: Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations. PRINCIPAL FINDINGS: Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats. CONCLUSIONS: sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

  19. CHRONIC UCL INJURY: A MULTIMODAL APPROACH TO CORRECTING ALTERED MECHANICS AND IMPROVING HEALING IN A COLLEGE ATHLETE— A CASE REPORT

    Science.gov (United States)

    Patrick, Rachel; McGinty, Josh; Lucado, Ann; Collier, Beth

    2016-01-01

    ABSTRACT Background Ulnar collateral ligament (UCL) tears and associated Tommy Johns surgical intervention from excessive and poor quality pitching has increased immensely—with more college and professional pitchers undergoing the surgery in 2014 alone than in the 1990s as a whole.1 Faulty mechanics developed at young ages are often well-engrained by the late adolescent years and the minimal healing ability of the largely avascular UCL often leads to delayed safe return to sport.2 Purpose The purpose of this case study was to describe an innovative, multimodal approach to conservative management of a chronic UCL injury in a college-aged baseball pitcher. This innovative approach utilizes both contractile and non-contractile dry needling to enhance soft tissue healing combined with standard conservative treatment to decrease pain and improve sport performance as measured by the Disabilities of Arm, Shoulder and Hand (DASH), Numeric Pain Report Scale (NPRS), and return to sport. Study Design Retrospective Case Report Case Description A collegiate athlete presented to an outpatient orthopedic physical therapy clinic for treatment of UCL sprain approximately six weeks post-injury and platelet-rich plasma injection. Diagnostic testing revealed chronic ligamentous microtrauma. Impairments at evaluation included proximal stabilizing strength deficits, myofascial trigger points throughout the dominant upper extremity, improper pitching form, and inability to pitch in game conditions due to severe pain. Interventions included addressing strength deficits throughout the body, dry needling, and sport-specific biomechanical training with pitching form analysis and correction. Outcomes Conventional DASH and Sport-Specific scale on the DASH and the numeric pain rating scale improved beyond both the minimally clinically important difference and minimal detectable change over the 12 week treatment3,4 At 24-week follow up, conventional DASH scores decreased from 34.20% disability

  20. Activation of ERK/CREB pathway in spinal cord contributes to chronic constrictive injury-induced neuropathic pain in rats

    Institute of Scientific and Technical Information of China (English)

    Xue-song SONG; Jun-li CAO; Yan-bing XU; Jian-hua HE; Li-cai ZHANG; Yin-ming ZENG

    2005-01-01

    Aim: To investigate whether activation and translocation of extracellular signalregulated kinase (ERK) is involved in the induction and maintenance of neuropathic pa in, and effects of activation and translocation of ERK on expression of pCREB and Fos in the chronic neuropathic pain.Methods: Lumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats.The left sciatic nerve was loosely ligated proximal to the sciatica's trifurcation at approximately 1.0 mm intervals with 4-0 silk sutures.The mitogen-activated protein kinase kinase (MEK) inhibitor U0126 or phosphorothioate-modified antisense oligonucleotides (ODN) were intrathecally administered every 12 h, 1 d pre-chronic constriction injury (CCI) and 3 d post-CCI.Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal latency (PWL) to radiant heat and yon Frey filaments.The expression of pERK, pCREB, and Fos were assessed by both Western blotting and immunohistochemical analysis.Results: Intrathecal injection of U0126 or ERK antisense ODN significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia.CCI significantly increased the expression of p-ERK-IR neurons in the ipsilateral spinal dorsal horn to injury, not in the contralateral spinal dorsal horn.The time courses of pERK expression showed that the levels of both cytosol and nuclear pERK, but not total ERK, were increased at all points after CCI and reached a peak level on postoperative d 5.CCI also significantly increased the expression of pCREB and Fos.Phospho-CREB-positive neurons were distributed in all laminae of the bilateral spinal cord and Fos was expressed in laminae Ⅰ and Ⅱ of the ipsilateral spinal dorsal horn.Intrathecal injection of U0126 or ERK antisense ODN markedly suppressed the increase of CCI-induced pERK, pCREB and c-Fos expression in the spinal cord.Conclusion:The activation of ERK pathways contributes to neuropathic pain in CCI rats, and the function of pERK may

  1. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation.

    Science.gov (United States)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak

    2015-10-01

    A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50mGy adapting dose administered acutely (0.40Gy/min) or chronically (1.4mGy/h or 4.1mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100mGy and 1Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50mGy at 1.4mGy/h followed by 1Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100mGy), no differences at the level of mutation were found comparing different dose rates.

  2. Expression changes of parvalbumin and microtubule-associated protein 2 induced by chronic constriction injury in rat dorsal root ganglia

    Institute of Scientific and Technical Information of China (English)

    CAO Ming-hui; JI Feng-tao; LIU Ling; LI Feng

    2011-01-01

    Background Parvalbumin (PV), as a mobile endogenous calcium buffer, plays an important role in affecting temporospatial characteristics of calcium transients and in modulating calcium homeostasis. PV is expressed in neurons in the dorsal root ganglion (DRG) and spinal dorsal horn and may be involved in synaptic transmission through regulating cytoplasm calcium concentrations. But the exact role of PV in peripheral sensory neurons remains unknown.Microtubule-associated protein 2 (MAP-2), belonging to structural microtubule-associated protein family, is especially vulnerable to acute central nervous system (CNS) injury, and there will be rapid loss of MAP-2 at the injury site. The present study investigated the changes of PV expressing neurons and the MAP-2 neurons in the DRG after an operation for chronic constriction injury to the unilateral sciatic nerve (CCI-SN), in order to demonstrate the possible roles of PV and MAP-2 in transmission and modulation of peripheral nociceptive information.Methods Seventy-two adult male Sprague-Dawley (SD) rats, weighing 180-220 g, were randomly divided into two groups (36 rats in each group), the sham operation group and chronic constriction injury (CCI) group. Six rats in each group were randomly selected to receive mechanical and thermal sensitivity tests at one day before operation and 1,3, 5,7, and 14 days after surgery. After pain behavioral test, ipsilateral lumbar fifth DRGs were removed and double immunofluorescence staining was performed to assess the expression changes of PV and of MAP2 expressing neurons in the L5 DRG before or after surgery.Results The animals with CCI-SN showed obvious mechanical allodynia and thermal hyperalgesia (P<0.05). Both the thermal and mechanical hyperalgesia decreased to their lowest degree at 7 days after surgery compared to the baseline before surgery (P<0.01). In normal rats before surgery, a large number of neurons were MAP-2 single labeled cells, and just a small number of PV

  3. The Control Strategies of Radiation Injuries to the Digestive System%核辐射对消化系统损害的防治策略

    Institute of Scientific and Technical Information of China (English)

    耿超; 林森

    2011-01-01

    消化系统中多个器官具有细胞代谢快、易受核射线损伤的特点,成为骨髓以外最容易遭受核辐射破坏的身体部位.日本核电站的泄露事故,使核辐射再度成为世界的焦点.随着人们对电离辐射认识的增加,核辐射对消化系统的损害也逐渐受到重视.本文通过对消化系统的损害机制的研究,论述了核辐射对消化系统的损害的防护和治疗策略.%Tissues and organs of the digestive system which often metabolize fast and are susceptible to the nuclear radiation are the most vulnerable to radiation injuries accept bone marrow. Recently, due to the leakage of Japanese nuclear power plant, people around the world focus on the problem of nuclear radiation once again. With increased understanding of ionizing radiation, radiation injuries to digestive system are gradually recognized. So this paper studies the mechanism of the digestive system injuries and discusses the prevention and treatment strategies for radiation injuries to digestive system.

  4. 放烧复合伤的治疗研究%Studies on the treatment of combined radiation-burn injury

    Institute of Scientific and Technical Information of China (English)

    程天民; 冉新泽

    2008-01-01

    Combined radiation-bum injuries mainly occur under the circumstances of nuclear explosion, nuclear accident, nuclear terrorism, depleted uranium attack, as well as secondary injuries following attack on nuclear installation. Combination of burn and radiation injuries bring along more serious whole body damage, more complicated pathological mechanism and much more difficult management. Research progress on the pathological mechanism and medical management of several key links of combined injury were discussed in this paper.①En-hancement of early first aid and prevention of early death of wounded. ②Damage and restoration of hemopoetic function.③Disturbance of immune function and prevention and treatment of infection (mainly on the intestinla mucosa immunity and enter-ological infection).④Management of burn wound.⑤The uole of several important measures in the comprehensive treatment.

  5. beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury

    DEFF Research Database (Denmark)

    Cordes, N; Seidler, J; Durzok, R;

    2006-01-01

    Integrin-mediated adhesion to extracellular matrix proteins confers resistance to radiation- or drug-induced genotoxic injury. To analyse the underlying mechanisms specific for beta1-integrins, wild-type beta1A-integrin-expressing GD25beta1A cells were compared to GD25beta1B cells, which express ...... in tumor cells may promote the development of innovative molecular-targeted therapeutic antitumor strategies.......Integrin-mediated adhesion to extracellular matrix proteins confers resistance to radiation- or drug-induced genotoxic injury. To analyse the underlying mechanisms specific for beta1-integrins, wild-type beta1A-integrin-expressing GD25beta1A cells were compared to GD25beta1B cells, which express...... signaling-incompetent beta1B variants. Cells grown on fibronectin, collagen-III, beta1-integrin-IgG or poly-l-lysine were exposed to 0-6 Gy X-rays in presence or depletion of growth factors and phosphatidylinositol-3 kinase (PI3K) inhibitors (LY294002, wortmannin). In order to test the relevance...

  6. Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

    Science.gov (United States)

    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

  7. Biochemical metabolic changes assessed by 31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    Ri-Sheng Yu; Liang Hao; Fei Dong; Jian-Shan Mao; Jian-Zhong Sun; Ying Chen; Min Lin; Zhi-Kang Wang; Wen-Hong Ding

    2009-01-01

    AIM:To compare the features of biochemical metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) with the liver damage score (LDS) and pathologic changes in rabbits and to investigate the diagnostic value of 31P MRS in acute hepatic radiation injury.METHODS:A total of 30 rabbits received different radiation doses (ranging 5-20 Gy) to establish acute hepatic injury models.Blood biochemical tests,31P MRS and pathological examinations were carried out 24 h after irradiation.The degree of injury was evaluated according to LDS and pathology.Ten healthy rabbits served as controls.The MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique.The relative quantities of phosphomonoesters (PME),phosphodiesters (PDE),inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured.The data were statistically analyzed.RESULTS:(1) Relative quantification of phosphorus metabolites:(a) ATP:there were significant differences (P<0.05) (LDS-groups:control group vs mild group vs moderate group vs severe group,1.83±0.33 vs 1.55±0.24 vs 1.27±0.09 vs 0.98±0.18;pathological groups:control group vs mild group vs moderate group vs severe group,1.83±0.33 vs 1.58±0.25 vs 1.32±0.07 vs 1.02 ± 0.18) of ATP relative quantification among control group,mild injured group,moderate injured group,and severe injured group according to both LDS grading and pathological grading,respectively,and it decreased progressively with the increased degree of injury (r=-0.723,P=0.000).(b) PME and Pi;the relative quantification of PME and Pi decreased significantly in the severe injured group,and the difference between the control group and severe injured group was significant (P<0.05) (PME:LDScontrol group vs LDS-severe group,0.86±0.23 vs 0.58±0.22,P=0.031;pathological control group vs pathological severe group,0.86±0.23 vs 0.60±0.21,P=0.037;Pi:LDS-control group vs LDS-severe group,0.74±0.18 vs

  8. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Xu Wu

    2016-01-01

    Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

  9. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  10. Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model.

    Directory of Open Access Journals (Sweden)

    Desirée L Salazar

    Full Text Available BACKGROUND: Traumatic spinal cord injury (SCI results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+ and CD24(-/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery. METHODS AND FINDINGS: hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein. CONCLUSIONS: The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for

  11. Retrospective analysis of linac-based radiosurgery for arteriovenous malformations and testing of the Flickinger formula in predicting radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Cetin, I.A. [Universitair Ziekenhuis Brussel (Belgium). Dept. of Radiation Oncology; Marmara Univ., Ustkaynarca/Pendik (Turkey). Dept. of Radiation Oncology; Ates, R.; Dhaens, J.; Storme, G. [Universitair Ziekenhuis Brussel (Belgium). Dept. of Radiation Oncology

    2012-12-15

    Background and purpose: The aim of the study was to validate the use of linac-based radiosurgery in arteriovenous malformation (AVM) patients and to predict complications using an integrated logistic formula (ILF) in comparison with clinical outcomes. Patients and methods: The results of radiosurgery in 92 AVM patients were examined. All patients were treated with linac-based radiosurgery. Of these, 70 patients were followed for 12-45 months (median, 24 months) and were analyzed. The treated volume varied from 0.09 to 26.95 cm{sup 3} (median, 2.3 cm{sup 3}) and the median marginal dose was 20 Gy (range, 10.4-22). The median 12-Gy volume was 9.94 cm{sup 3} (range, 0.74-60.09 cm{sup 3}). Patients and lesion characteristics potentially affecting nidus obliteration and excellent outcome were evaluated by performing a log-rank test and univariate and multivariate analyses. The risk for radiation injury (RRI) was calculated with an integrated logistic formula. The predictive power of the RRI was assessed by calculating the area under the receiver operating characteristic (ROC) curve. Results: Follow-up magnetic resonance (MR) angiography revealed complete AVM obliteration in 56 of 70 patients. The MR angiography confirmed an obliteration rate of 80%. The annual hemorrhage rate was 1.4% for the first 2 years after radiosurgery and 0% thereafter. The number of patients with an excellent outcome was 48 (68%). Factors associated with better obliteration were higher radiation dose to the lesion margins [12-Gy volume (V12) > 10 cm{sup 3}], small volume, and a Pollock-Flickinger score less than 1.49; those predicting excellent outcomes were V12 < 10 cm{sup 3}, small volume, and Pollock-Flickinger score less than 1.49, as determined by multivariate analyses. Factors associated with radiation injury were V12 > 10 cm{sup 3} (p=0.03) and volume greater than 2 cm{sup 3} (p=0.001), as determined by a univariate analysis. The analyses showed an ROC of 0.66. Conclusion: These data

  12. Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Foro, Palmira, E-mail: pforo@parcdesalutmar.cat [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Algara, Manuel [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Lozano, Joan [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Rodriguez, Nuria; Sanz, Xavier [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Torres, Erica [Pathology Department, Parc de Salut Mar, Barcelona (Spain); Carles, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Department of Oncology, Hospital Vall d' Hebron, Barcelona (Spain); Reig, Anna; Membrive, Ismael [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Quera, Jaume [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Fernandez-Velilla, Enric; Pera, Oscar [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Lacruz, Marti [Universitat Pompeu Fabra, Barcelona (Spain); Radiation Protection Department, Parc de Salut Mar, Barcelona (Spain); Bellosillo, Beatriz [Universitat Pompeu Fabra, Barcelona (Spain); Pathology Department, Parc de Salut Mar, Barcelona (Spain)

    2014-04-01

    Purpose: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. Methods and Materials: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. Results: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). Conclusions: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of

  13. Persistent at-level thermal hyperalgesia and tactile allodynia accompany chronic neuronal and astrocyte activation in superficial dorsal horn following mouse cervical contusion spinal cord injury.

    Science.gov (United States)

    Watson, Jaime L; Hala, Tamara J; Putatunda, Rajarshi; Sannie, Daniel; Lepore, Angelo C

    2014-01-01

    In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation), persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression), and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to neuropathic pain

  14. Clinical Management of a Patient with Chronic Recurrent Vertigo Following a Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Eric G. Johnson

    2009-01-01

    Full Text Available Vertigo, was provoked and right torsional up-beat nystagmus was observed in a 47-year-old patient when she was placed into the right Hallpike-Dix test position using infrared goggle technology. The clinical diagnosis was benign paroxysmal positional vertigo (BPPV, specifically right posterior canalithiasis, resulting from a mild traumatic brain injury (TBI suffered approximately six-months earlier. Previous medical consultations did not include vestibular system examination, and Meclizine was prescribed to suppress her chief complaint of vertigo. Ultimately, the patient was successfully managed by performing two canalith repositioning maneuvers during a single clinical session. The patient reported 100% resolution of symptoms upon reexamination the following day, and the Hallpike-Dix test was negative. Continued symptom resolution was subjectively reported 10 days postintervention via telephone consultation. This case report supports previous publications concerning the presence of BPPV following TBI and the need for inclusion of vestibular system examination during medical consultation.

  15. Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

    Science.gov (United States)

    Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

    2016-11-01

    Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine.

  16. Sex-dependent effects of chronic psychosocial stress on myocardial sensitivity to ischemic injury.

    Science.gov (United States)

    Rorabaugh, Boyd R; Krivenko, Anna; Eisenmann, Eric D; Bui, Albert D; Seeley, Sarah; Fry, Megan E; Lawson, Joseph D; Stoner, Lauren E; Johnson, Brandon L; Zoladz, Phillip R

    2015-01-01

    Individuals with post-traumatic stress disorder (PTSD) experience many debilitating symptoms, including intrusive memories, persistent anxiety and avoidance of trauma-related cues. PTSD also results in numerous physiological complications, including increased risk for cardiovascular disease (CVD). However, characterization of PTSD-induced cardiovascular alterations is lacking, especially in preclinical models of the disorder. Thus, we examined the impact of a psychosocial predator-based animal model of PTSD on myocardial sensitivity to ischemic injury. Male and female Sprague-Dawley rats were exposed to psychosocial stress or control conditions for 31 days. Stressed rats were given two cat exposures, separated by a period of 10 days, and were subjected to daily social instability throughout the paradigm. Control rats were handled daily for the duration of the experiment. Rats were tested on the elevated plus maze (EPM) on day 32, and hearts were isolated on day 33 and subjected to 20 min ischemia and 2 h reperfusion on a Langendorff isolated heart system. Stressed male and female rats gained less body weight relative to controls, but only stressed males exhibited increased anxiety on the EPM. Male, but not female, rats exposed to psychosocial stress exhibited significantly larger infarcts and attenuated post-ischemic recovery of contractile function compared to controls. Our data demonstrate that predator stress combined with daily social instability sex-dependently increases myocardial sensitivity to ischemic injury. Thus, this manipulation may be useful for studying potential mechanisms underlying cardiovascular alterations in PTSD, as well as sex differences in the cardiovascular stress response.

  17. Fibroblast growth factor-2 induced by enriched environment enhances angiogenesis and motor function in chronic hypoxic-ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    Jung Hwa Seo

    Full Text Available This study aimed to investigate the effects of enriched environment (EE on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI brain injury. HI brain damage was induced in seven day-old CD-1® mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2 was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1 and α-smooth muscle actin (α-SMA were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of α-SMA(+ and PECAM-1(+ cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions

  18. High-volume FES-cycling partially reverses bone loss in people with chronic spinal cord injury.

    Science.gov (United States)

    Frotzler, Angela; Coupaud, Sylvie; Perret, Claudio; Kakebeeke, Tanja H; Hunt, Kenneth J; Donaldson, Nick de N; Eser, Prisca

    2008-07-01

    Spinal cord injury (SCI) leads to severe bone loss in the paralysed limbs and to a resulting increased fracture risk thereof. Since long bone fractures can lead to comorbidities and a reduction in quality of life, it is important to improve bone strength in people with chronic SCI. In this prospective longitudinal cohort study, we investigated whether functional electrical stimulation (FES) induced high-volume cycle training can partially reverse the loss of bone substance in the legs after chronic complete SCI. Eleven participants with motor-sensory complete SCI (mean age 41.9+/-7.5 years; 11.0+/-7.1 years post injury) were recruited. After an initial phase of 14+/-7 weeks of FES muscle conditioning, participants performed on average 3.7+/-0.6 FES-cycling sessions per week, of 58+/-5 min each, over 12 months at each individual's highest power output. Bone and muscle parameters were investigated in the legs by means of peripheral quantitative computed tomography before the muscle conditioning (t1), and after six (t2) and 12 months (t3) of high-volume FES-cycle training. After 12 months of FES-cycling, trabecular and total bone mineral density (BMD) as well as total cross-sectional area in the distal femoral epiphysis increased significantly by 14.4+/-21.1%, 7.0+/-10.8% and 1.2+/-1.5%, respectively. Bone parameters in the femoral shaft showed small but significant decreases, with a reduction of 0.4+/-0.4% in cortical BMD, 1.8+/-3.0% in bone mineral content, and 1.5+/-2.1% in cortical thickness. These decreases mainly occurred between t1 and t2. No significant changes were found in any of the measured bone parameters in the tibia. Muscle CSA at the thigh increased significantly by 35.5+/-18.3%, while fat CSA at the shank decreased by 16.7+/-12.3%. Our results indicate that high-volume FES-cycle training leads to site-specific skeletal changes in the paralysed limbs, with an increase in bone parameters at the actively loaded distal femur but not the passively loaded

  19. WE-D-BRE-01: A Sr-90 Irradiation Device for the Study of Cutaneous Radiation Injury

    Energy Technology Data Exchange (ETDEWEB)

    Dorand, JE; Bourland, JD [Department of Radiation Oncology and Department of Physics, Wake Forest University, Winston-Salem, NC (United States); Burnett, LR [KeraNetics, LLC, Winston-Salem, NC (United States); Tytell, M [Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC (United States)

    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

  20. Somatosensory inputs by application of KinesioTaping: Effects on spasticity, balance, and gait in chronic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Federica eTamburella

    2014-05-01

    Full Text Available Introduction: Leg paralysis, spasticity, reduced inter limb coordination and impaired balance are considered the chief limitations to overground ambulation in subjects with incomplete spinal cord injury (SCI. In the last years KinesioTaping (KT application has been proposed for enhancing sensory inputs, decreasing spasticity via proprioception feedback and relieving abnormal muscle tension. No studies addressed KT technique on SCI subjects: our goal was to analyze effects of ankle joint KT application on spasticity, balance and gait. Material and Methods: A randomized cross-over case control design was used to compare KT and conventional non-elastic silk tape (ST application’s effects in 11 chronic SCI subjects, AIS level D, with soleus/gastrocnemius (S/G muscles’ spasticity , balance and gait impairments. Treatment: 48 hours of either KT or ST treatment was followed after 1 week interval by a reverse protocol. Patient treated with KT were subjected to 48 hours of ST treatment and viceversa. Single Y-stripe of Cure©tape (KT and ST were applied to S and G with 0% stretch. Before and after 48 hours of KT and ST application, clinical data of range of motion (ROM, spasticity, clonus, pain, balance and gait were collected. Stabilometric platform assessment of Centre of Pressure (COP movements, bi-dimensional gait analysis and electromyograpich (EMG activity of S, G, Tibialis Anterior and Extensor Hallicus Lungus muscles were also collected. Results: Only After KT treatment significant effects on spasticity, clonus and COP movements, kinematic gait parameters and EMG activities were recorded. Comparison between KT and ST improvements pointed out significant differences for ROM, spasticity, clonus, pain, COP parameters and most of all kinematic gait data. Discussion: KT short term application reduces spasticity and pain and improves balance and gait performances in chronic incomplete SCI subjects.

  1. Cytokine profiles and hepatic injury in occult hepatitis C versus chronic hepatitis C virus infection.

    Science.gov (United States)

    Mousa, N; Eldars, W; Eldegla, H; Fouda, O; Gad, Y; Abousamra, N; Elmasry, E; Arafa, M

    2014-01-01

    Occult hepatitis C virus (HCV) infection is a new entity that should be considered when diagnosing patients with abnormal liver functions of unknown origin. This work was carried out to evaluate T-helper 1/T-helper 2 (Th1/Th2) cytokine profiles in patients with occult HCV infection versus chronic hepatitis C (CHC) infection, also to investigate any association between theses cytokines and liver histological features in both groups. Serum levels of Th1 cytokines (IL-2, IFN-gamma) and Th2 (IL-4 and IL-10) were measured in 35 patients with occult HCV infection compared to 50 patients with chronic hepatitis C infection and 30 healthy controls. We have found that Th1 cytokines were significantly increased in patients with CHC infection than in both occult HCV infection and control groups (p less than 0.001). On the other hand, serum IL-4 levels were higher in occult HCV infection than in CHC and control groups (p less than 0.001). Furthermore, serum IL-10 levels were higher in both patient groups vs control group (pless than 0.001), with no significant difference between CHC and occult HCV groups. Finally, only serum IL-10 levels were significantly higher among patients with high activity (A2-A3) than those with low activity (A0-A1) in both CHC and occult HCV groups (p=0.038, p=0.025, respectively). Patients with occult HCV infection exhibited a distinct immunoregulatory cytokine pattern that is shifted towards the Th2 arm.

  2. Disruption of caudate working memory activation in chronic blast-related traumatic brain injury

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    Mary R. Newsome

    2015-01-01

    Full Text Available Mild to moderate traumatic brain injury (TBI due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes. Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate. Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results

  3. p300 exerts an epigenetic role in chronic neuropathic pain through its acetyltransferase activity in rats following chronic constriction injury (CCI

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    Zhu Xiao-Yan

    2012-11-01

    Full Text Available Abstract Background Neuropathic pain is detrimental to human health; however, its pathogenesis still remains largely unknown. Overexpression of pain-associated genes and increased nociceptive somato-sensitivity are well observed in neuropathic pain. The importance of epigenetic mechanisms in regulating the expression of pro- or anti-nociceptive genes has been revealed by studies recently, and we hypothesize that the transcriptional coactivator and the histone acetyltransferase E1A binding protein p300 (p300, as a part of the epigenetic mechanisms of gene regulation, may be involved in the pathogenesis of neuropathic pain induced by chronic constriction injury (CCI. To test this hypothesis, two different approaches were used in this study: (I down-regulating p300 with specific small hairpin RNA (shRNA and (II chemical inhibition of p300 acetyltransferase activity by a small molecule inhibitor, C646. Results Using the CCI rat model, we found that the p300 expression was increased in the lumbar spinal cord on day 14 after CCI. The treatment with intrathecal p300 shRNA reversed CCI-induced mechanical allodynia and thermal hyperalgesia, and suppressed the expression of cyclooxygenase-2 (COX-2, a neuropathic pain-associated factor. Furthermore, C646, an inhibitor of p300 acetyltransferase, also attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord. Conclusions The results suggest that, through its acetyltransferase activity in the spinal cord after CCI, p300 epigenetically plays an important role in neuropathic pain. Inhibiting p300, using interfering RNA or C646, may be a promising approach to the development of new neuropathic pain therapies.

  4. A Diathesis-Stress Model of Chronic Pain and Disability following Traumatic Injury

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    Dennis C Turk

    2002-01-01

    Full Text Available One of the perplexing features of pain is the wide variability in patients' responses to ostensibly the same extent of physical pathology. A range of cognitive, affective and behavioural factors are related to the perception of pain, maintenance of pain and disability, exacerbation of pain and response to treatment. Moreover, there is some evidence that individual differences and prior learning history also have a significant influence on the experience of pain and related disability. The role of these psychological factors in the maintenance of disability following traumas such as motor vehicle accidents and work-related injuries has generated considerable interest. This paper provides a brief overview of a set of predisposing factors, cognitive processes and behavioural principles that appear to be particularly important in the maintenance of disability following trauma. In particular, anxiety sensitivity, anticipation and avoidance of fear or harm, catastrophizing ideation, causal attributions for symptoms, self-efficacy and operant conditioning are discussed. Each of these factors is integrated in a diathesis-stress model that emphasizes the interaction of predisposing factors with a trauma, setting in motion a cascade of interpretive cognitive processes and reinforcement contingencies that maintain disability following the trauma. This model proposes a sequential process to explain the variation observed among people following a relatively minor trauma. The model is intended to be heuristic. It may be a useful conceptualization that can serve to guide prevention efforts and the development of treatment interventions.

  5. Hyperbaric oxygen in chronic traumatic brain injury: oxygen, pressure, and gene therapy.

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    Harch, Paul G

    2015-01-01

    Hyperbaric oxygen therapy is a treatment for wounds in any location and of any duration that has been misunderstood for 353 years. Since 2008 it has been applied to the persistent post-concussion syndrome of mild traumatic brain injury by civilian and later military researchers with apparent conflicting results. The civilian studies are positive and the military-funded studies are a mixture of misinterpreted positive data, indeterminate data, and negative data. This has confused the medical, academic, and lay communities. The source of the confusion is a fundamental misunderstanding of the definition, principles, and mechanisms of action of hyperbaric oxygen therapy. This article argues that the traditional definition of hyperbaric oxygen therapy is arbitrary. The article establishes a scientific definition of hyperbaric oxygen therapy as a wound-healing therapy of combined increased atmospheric pressure and pressure of oxygen over ambient atmospheric pressure and pressure of oxygen whose main mechanisms of action are gene-mediated. Hyperbaric oxygen therapy exerts its wound-healing effects by expression and suppression of thousands of genes. The dominant gene actions are upregulation of trophic and anti-inflammatory genes and down-regulation of pro-inflammatory and apoptotic genes. The combination of genes affected depends on the different combinations of total pressure and pressure of oxygen. Understanding that hyperbaric oxygen therapy is a pressure and oxygen dose-dependent gene therapy allows for reconciliation of the conflicting TBI study results as outcomes of different doses of pressure and oxygen.

  6. A multidisciplinary cognitive behavioural programme for coping with chronic neuropathic pain following spinal cord injury: the protocol of the CONECSI trial

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    Dijkstra Catja A

    2010-10-01

    Full Text Available Abstract Background Most people with a spinal cord injury rate neuropathic pain as one of the most difficult problems to manage and there are no medical treatments that provide satisfactory pain relief in most people. Furthermore, psychosocial factors have been considered in the maintenance and aggravation of neuropathic spinal cord injury pain. Psychological interventions to support people with spinal cord injury to deal with neuropathic pain, however, are sparse. The primary aim of the CONECSI (COping with NEuropathiC Spinal cord Injury pain trial is to evaluate the effects of a multidisciplinary cognitive behavioural treatment programme on pain intensity and pain-related disability, and secondary on mood, participation in activities, and life satisfaction. Methods/Design CONECSI is a multicentre randomised controlled trial. A sample of 60 persons with chronic neuropathic spinal cord injury pain will be recruited from four rehabilitation centres and randomised to an intervention group or a waiting list control group. The control group will be invited for the programme six months after the intervention group. Main inclusion criteria are: having chronic (> 6 months neuropathic spinal cord injury pain as the worst pain complaint and rating the pain intensity in the last week as 40 or more on a 0-100 scale. The intervention consists of educational, cognitive, and behavioural elements and encompasses 11 sessions over a 3-month period. Each meeting will be supervised by a local psychologist and physical therapist. Measurements will be perfomed before starting the programme/entering the control group, and at 3, 6, 9, and 12 months. Primary outcomes are pain intensity and pain-related disability (Chronic Pain Grade questionnaire. Secondary outcomes are mood (Hospital Anxiety and Depression Scale, participation in activities (Utrecht Activities List, and life satisfaction (Life Satisfaction Questionnaire. Pain coping and pain cognitions will be

  7. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

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    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application.

  8. Prediction of posttraumatic stress in fathers of children with chronic diseases or unintentional injuries: a six-months follow-up study

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    Sennhauser Felix H

    2007-12-01

    Full Text Available Abstract Background While fathers were neglected for a long time in research investigating families of pediatric patients, there are now a few studies available on fathers' posttraumatic stress symptoms (PTSS and posttraumatic stress disorder (PTSD. However, little is known about the course of PTSS and PTSD in fathers of pediatric patients. The present study aimed to compare the prevalence and course of PTSS and PTSD in fathers of children with different chronic and acute conditions and to identify factors that contribute to fathers' PTSS. Methods Sixty-nine fathers of children newly diagnosed with either cancer, type I diabetes mellitus, or epilepsy and 70 fathers of children suffering from an unintentional injury completed questionnaires at 4–6 weeks (Time 1 and six months (Time 2 after diagnosis or injury. Results Noticeable PTSD rates were found in fathers of children with a chronic disease (26% at Time 1 and 21% at Time 2, respectively. These rates were significantly higher than rates found in fathers of children with unintentional injuries (12% at Time 1 and 6% at Time 2, respectively. Within six months after the child's diagnosis or accident a decrease in severity of PTSS was observed in both groups. Significant predictors of PTSS at Time 2 were the father's initial level of PTSS, the child's medical condition (injuries vs. chronic diseases and functional status, the father's use of dysfunctional coping strategies, and father's level of neuroticism. Conclusion Our findings suggest that fathers with initially high PTSS levels are at greater risk to experience PTSS at follow-up, particularly fathers of children with a chronic disease. Sensitizing health care professionals to the identification of PTSS symptoms but also to indicators of neuroticism and the use of specific coping strategies early in the treatment course is essential for the planning and implementation of adequate intervention strategies.

  9. The Effect of Alternating Current Iontophoresis on Rats with the Chronic Constriction Injury to the Infraorbital Nerve

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    Yoko Yamazaki

    2012-01-01

    Full Text Available This study aimed to examine the effect of AC iontophoresis on rats with the chronic constriction injury (CCI to the infraorbital nerve by animal experiments. CCI model rats were divided into four groups, namely, rats that received general anesthesia for 60 min except AC IOP (CCI: n=5, AC IOP with 0.9% physiological saline for 60 min (CCI + saline AC IOP: n=5, AC IOP with 4% lidocaine hydrochloride for 60 min (CCI + lidocaine AC IOP: n=5, and attachment of two electrodes soaked with 4% lidocaine hydrochloride to the facial skin for 60 min (CCI + attach lidocaine: n=5. In the CCI + lidocaine AC IOP group, an elevated withdrawal threshold was observed after AC IOP, and the duration of efficacy was longer compared with that in the CCI + saline AC IOP and CCI + attached lidocaine groups. A significant decrease in the number of Fos-like immunoreactive (LI cells was observed in the CCI + lidocaine AC IOP group compared with that in the CCI group. These findings suggest that the effect of CCI + lidocaine AC IOP group may be caused by active permeation of lidocaine into the facial skin and electrical stimulation of the trigeminal nucleus.

  10. The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.

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    Corona-Ramos, Janette Nallely; De la O-Arciniega, Minarda; Déciga-Campos, Myrna; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

    2016-08-01

    Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016.   © 2016 Wiley Periodicals, Inc.

  11. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

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    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-01-01

    Aim: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Methods: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1H-NMR-based metabolomic analysis. Results: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Conclusion: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The 1H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines. PMID:24632844

  12. Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

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    VENKATA R.K. THIAGARAJAN

    2014-09-01

    Full Text Available The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

  13. Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

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    Mehta, Ashish K; Bhati, Yogendra; Tripathi, Chakra D; Sharma, Krishna K

    2014-08-01

    Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

  14. Somatic symptoms beyond those generally associated with a whiplash injury are increased in self-reported chronic whiplash. A population-based cross sectional study: the Hordaland Health Study (HUSK

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    Myrtveit Solbjørg

    2012-08-01

    Full Text Available Abstract Background Chronic whiplash leads to considerable patient suffering and substantial societal costs. There are two competing hypothesis on the etiology of chronic whiplash. The traditional organic hypothesis considers chronic whiplash and related symptoms a result of a specific injury. In opposition is the hypothesis that chronic whiplash is a functional somatic syndrome, and related symptoms a result of society-induced expectations and amplification of symptoms. According to both hypotheses, patients reporting chronic whiplash are expected to have more neck pain, headache and symptoms of anxiety and depression than the general population. Increased prevalence of somatic symptoms beyond those directly related to a whiplash neck injury is less investigated. The aim of this study was to test an implication derived from the functional hypothesis: Is the prevalence of somatic symptoms as seen in somatization disorder, beyond symptoms related to a whiplash neck injury, increased in individuals self-reporting chronic whiplash? We further aimed to explore recall bias by comparing the symptom profile displayed by individuals self-reporting chronic whiplash to that among those self-reporting a non-functional injury: fractures of the hand or wrist. We explored symptom load, etiologic origin could not be investigated in this study. Methods Data from the Norwegian population-based “Hordaland Health Study” (HUSK, 1997–99; N = 13,986 was employed. Chronic whiplash was self-reported by 403 individuals and fractures by 1,746. Somatization tendency was measured using a list of 17 somatic symptoms arising from different body parts and organ systems, derived from the research criteria for somatization disorder (ICD-10, F45. Results Chronic whiplash was associated with an increased level of all 17 somatic symptoms investigated (p Conclusions The increased prevalence of somatic symptoms beyond symptoms expected according to the organic injury model

  15. Pilot study of the effects of mixed light touch manual therapies on active duty soldiers with chronic post-traumatic stress disorder and injury to the head.

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    Davis, Lauren; Hanson, Brenda; Gilliam, Sara

    2016-01-01

    This pilot study was designed to examine the effects of mixed Light Touch Manual Therapies (LTMT) on headache, anxiety and other symptoms suffered by active duty United States service members experiencing chronic Post-Traumatic Stress Disorder (PTSD). Ten service members diagnosed with PTSD and having a self-reported injury to the head acquired at least two years prior, were provided with two hour-long sessions of mixed LTMT given a week apart. Data to assess the immediate and durable effects were gathered before and after the LTMT sessions. Results indicate that headache, anxiety, and pain interference were significantly reduced during the course of the pilot study. This suggests that mixed LTMT may be helpful in reducing some of the symptoms of PTSD and injury to the head. Further studies will be needed to determine if LTMT is an effective non-pharmacological treatment for headache, anxiety or other problems associated with PTSD or injury to the head.

  16. Patients with Chronic Spinal Cord Injury Exhibit Reduced Autonomic Modulation during an Emotion Recognition Task

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    Varas-Díaz, Gonzalo; Brunetti, Enzo P.; Rivera-Lillo, Gonzalo; Maldonado, Pedro E.

    2017-01-01

    Spinal cord injury (SCI) is a devastating event for individuals, who frequently develop motor and sensory impairment as well as autonomic dysfunction. Previous studies reported that autonomic activity plays a major role in social cognition and that difficulties in the ability to interpret social information are commonly observed in a variety of mental disorders, which in turn correlate with a poor autonomic nervous system (ANS) regulation. It is well established that subjects with SCI have an alteration in ANS regulation mechanisms. We hypothesized that subjects diagnosed with SCI, who are experiencing a period of adaptation and socio-labor insertion suffer alterations in an emotion recognition task, a component of social cognition, which correlate with poor ANS regulation. We evaluated ANS function by measuring the heart rate variability (HRV) in 18 healthy subjects and 10 subjects with SCI. A 5-min baseline HRV was compared to a task period while performing The reading the mind in the eyes test (RMET). We found that while both groups have similar general performance in the test, healthy subjects responded with greater certainty during the RMET. This level of certainty during the RMET was positively correlated with baseline HRV measures in this group. Also, the group of healthy subjects exhibited higher HRV at baseline than participants with SCI. Finally, the changes in HRV between baseline and task condition were significantly higher in healthy individuals than in SCI participants. Our results show that patients with SCI have low levels of autonomic regulation mechanisms which may promote social cognition problems during their reinsertion to daily life. PMID:28228721

  17. The use of low intensity laser radiation in the treatment of patients with closed traumatic brain injury consequences

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    Kolesov V.N.

    2016-06-01

    Full Text Available Objective: to determine the effectiveness of the use of low-intensity helium-neon laser radiation in patients with post-traumatic cerebral arachnoiditis. Material and Methods. We observed 164 patients with the effects of closed craniocerebral injuries of a various severity. Methods of percutaneous laser irradiation of blood in the projection of the common carotid artery at the level of IV cervical vertebra was carried out underthe supervision of the clinical evaluation of hemodynamic data survey methods. Results. Positive results of hemodynamic parameters of examination methods indicate regression of cerebral vasospasm and improving brain vascular reserve, which led to a decrease in cerebral and focal neurological symptoms. Conclusion. The method allows the use of this technique in these patients both in the hospital and at the outpatient stage.

  18. Protection of Effective Component Group from Xiaoshuan Tongluo on Brain Injury after Chronic Hypoperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    TAN Chu-bing; WANG Hong-qing; TIAN Shuo; GAO Mei; XU Wei-ren; CHEN Ruo-yun; DU Guan-hua

    2011-01-01

    Objective To investigate the protective effects of purified effective component group in extract from Xiaoshuan Tongluo(CGXT)formula on chronic brain ischemia in rats.Methods CGXT 75,150,and 300 mg/kg or vehicle were ig administered daily for four weeks to rats with bilateral common carotid arteries ligation(BCCAL).From the day 24 to 28 after BCCAL,Morris water maze was performed to assess the learning and memory impairment of rats.Four weeks after BCCAL,brain gray and white matter damage were assessed.Results In Morris test,the mean escape latency of rats in the CGXT(150 and 300 mg/kg)groups was significantly shorter than that in the vehicle group.CGXT also attenuated the neuronal damage in hippocampus and cortex and reduced the pathological damage in the optic tract and corpus callosum.Conclusion CGXT could improve learning and memory impairment resulted from BCCAL in rats.These results provide the experimental basis for the clinical use of CGXT in stroke treatment and may help in investigation of multimodal therapy strategies in ischemic cerebrovascular diseases including stroke.

  19. Studies on chemical protectors against radiation, 34; Survival effects of aqueous extracts of various Chinese traditional medicines on radiation injury

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    Wang, Cheng-Ming; Ohta, Setsuko; Shinoda, Masato (Hoshi Univ., Tokyo (Japan))

    1991-06-01

    In order to develop a nontoxic radioprotector, 60 kinds of Chinese traditional medicines were chosen, and their aqueous extracts tested for their survival effects against the lethal effect of X-irradiation in mice. Radiation factors used were as follows: soft X-rays, 2100 R (5.418x10{sup -1}Ckg{sup -1}), 70 kVp, 10 mA, 10 mm acrylic filter, 70 R (1.806x10{sup -2} Ckg{sup -1})/min. Among 60 medicines tested by intraperitoneal injection immediately before the irradiation, 15 are shown to have the significant survival effect. These 15 effective medicines were also tested by intraperitoneal injection after the irradiation, and the survival effect was recognized in Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Shimotu-to, Syakuyaku-kanzo-to and Hange-syasin-to. On the other hand, the survival effects of 25 medicines including the above-mentioned 15 medicines were investigated by the oral administration at various times before or after the irradiation. As the results of these studies, only Keigai-rengyo-to and Bukuryo-in are shown to have the significant survival effect when administered 2 h before the irradiation. (author).

  20. Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant Extract

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    Priyanka Sharma

    2011-01-01

    Full Text Available 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.

  1. Potential protection of green tea polyphenols against 1800 MHz electromagnetic radiation-induced injury on rat cortical neurons.

    Science.gov (United States)

    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.

  2. Modulation of Mortality by Tissue Trauma and Sepsis in Mice after Radiation Injury

    Science.gov (United States)

    1992-01-01

    States, and Chernobyl, U.S.S.R.) and from abandoned medical radiation devices (Juarez, Mexico, and Goiania , Brazil). Th ;nceased risk to human health as...well as the loss of life in Chernobyl and Goiania have had sobering influences upon the world. 202 92-19333 92 o J1 I l ~l ,,TIIII,1 .\\hodtatlon Of...exposed to radiation in the accident at Goiania (Brandao-Mello et al. 1991, Butturini et al. 1988). Several patients responded to GM-CSF with

  3. Effect of electrosleep therapy on the course and outcome of radiation injuries in animals

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    Dzhavadyan, N.S.; Abgaryan, D.V.; Neifets, Yu.B.

    1974-01-01

    Experimental data are presented with regard to the effect of electrosleep therapy on the course of severe radiation sickness and the survival of animals (rabbits and dogs). The results of the studies showed that the use of a number of electrosleep seances before irradiation, and especially, in the first two weeks after irradiation had a favorable effect on the course of the severe radiation sickness, as expressed in the slow and relatively weak development of leucopenia and in the high percentage of animal survivals. 13 refs. (SJR)

  4. Subcutis calcinosis caused by injection of calcium-containing heparin in a chronic kidney injury patient.

    Science.gov (United States)

    Fatma, Lilia Ben; El Ati, Zohra; Azzouz, Haifa; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hédi Ben; Béji, Soumaya; Zouaghi, Karim; Zitouna, Moncef; Moussa, Fatma Ben

    2014-09-01

    Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD) for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcutaneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin) that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadroparin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calciphylaxis, outcome is favorable.

  5. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I. [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Watson, Walter H. [Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Zhong, Hai [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); States, J. Christopher [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Arteel, Gavin E., E-mail: gavin.arteel@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States)

    2011-12-15

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet ({+-} arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: Black-Right-Pointing-Pointer Characterizes a mouse model of arsenic enhanced NAFLD. Black-Right-Pointing-Pointer Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. Black-Right-Pointing-Pointer This effect is associated with increased inflammation.

  6. Subcutis calcinosis caused by injection of calcium-containing heparin in a chronic kidney injury patient

    Directory of Open Access Journals (Sweden)

    Lilia Ben Fatma

    2014-01-01

    Full Text Available Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcu-taneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadro-parin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calci-phylaxis, outcome is favorable.

  7. Overexpression of Extracellular Superoxide Dismutase Protects against Brain Injury Induced by Chronic Hypoxia

    Science.gov (United States)

    Zaghloul, Nahla; Patel, Hardik; Codipilly, Champa; Marambaud, Philippe; Dewey, Stephen; Frattini, Stephen; Huerta, Patricio T.; Nasim, Mansoor; Miller, Edmund J.; Ahmed, Mohamed

    2014-01-01

    Extracellular superoxide dismutase (EC-SOD) is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1%) for 10 days (H-KI) and compared to transgenic animals housed in room air (RA-KI), wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT). Overall brain metabolism evaluated by positron emission tomography (PET) showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation. PMID:25268361

  8. Overexpression of extracellular superoxide dismutase protects against brain injury induced by chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Nahla Zaghloul

    Full Text Available Extracellular superoxide dismutase (EC-SOD is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1% for 10 days (H-KI and compared to transgenic animals housed in room air (RA-KI, wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT. Overall brain metabolism evaluated by positron emission tomography (PET showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation.

  9. Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Borrego-Soto, Gissela; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto, E-mail: arojasmtz@gmail.com, E-mail: augusto.rojasm@uanl.mx [Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León (Mexico)

    2015-10-15

    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. (author)

  10. Whiplash injuries.

    Science.gov (United States)

    Malanga, Gerard; Peter, Jason

    2005-10-01

    Whiplash injuries are very common and usually are associated with rear-end collisions. However, a whiplash injury can be caused by any event that results in hyperextension and flexion of the cervical spine. These injuries are of serious concern to all consumers due to escalating cost of diagnosis, treatment, insurance, and litigation. Most acute whiplash injury cases respond well to conservative treatments, which result in resolution of symptoms usually within weeks to a few months after the injury occurred. Chronic whiplash injuries often are harder to diagnose and treat and often result in poor outcomes. Current research shows that various structures in the cervical spine receive nociceptive innervation and potentially may be the cause of chronic pain symptoms. One potential pain generator showing promise is the facet or zygapophyseal joints. Various researchers have proven that these joints are injured during whiplash injuries and that diagnosis and temporary pain relief can be obtained with facet joint injections. The initial evaluation of any patient should follow an organized and stepwise approach, and more serious causes of neck pain must first be ruled out through the history, physical examination, and diagnostic testing. Treatment regimens should be evidence-based, focusing on treatments that have proven to be effective in treating acute and chronic whiplash injuries.

  11. An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy

    Directory of Open Access Journals (Sweden)

    Rifkin Lucas H

    2012-05-01

    Full Text Available Abstract Purpose To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury. Methods A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD. Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software. Results No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664. Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753. With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895. Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint. Conclusions We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

  12. Surgical treatment of acute and chronic anterior and posterior cruciate ligament and medial-side injuries of the knee.

    Science.gov (United States)

    Hubert, Mark G; Stannard, James P

    2011-06-01

    KD-IIIM knee injuries are challenging injuries that can do well when anatomic reconstruction techniques are used. This article describes the authors preferred reconstructions, timing of surgery, and rehabilitation techniques. The reconstructions are generally initiated 3 or 4 weeks after the injury when the local soft tissue injury allows and associated fractures have already been stabilized. The posterior cruciate ligament, posteromedial corner, and meniscus injuries are addressed in the initial operation. The corresponding author prefers to come back 6 weeks later and reconstruct the anterior cruciate ligament and assure that acceptable progress has been made regarding knee motion.

  13. Gene Mutation as Biomarker of Radiation Induced Cell Injury and Genomic Instability

    Directory of Open Access Journals (Sweden)

    M Syaifudin

    2006-07-01

    Full Text Available Gene expression profiling and its mutation has become one of the most widely used approaches to identify genes and their functions in the context of identify and categorize genes to be used as radiation effect markers including cell and tissue sensitivities. Ionizing radiation produces genetic damage and changes in gene expression that may lead to cancer due to specific protein that controlling cell proliferation altered the function, its expression or both. P53 protein encoded by p53 gene plays an important role in protecting cell by inducing growth arrest and or cell suicide (apoptosis after deoxyribonucleic acid (DNA damage induced by mutagen such as ionizing radiation. The mutant and thereby dysfunctional of this gene was found in more than 50% of various human cancers, but it is as yet unclear how p53 mutations lead to neoplastic development. Wild-type p53 has been postulated to play a role in DNA repair, suggesting that expression of mutant forms of p53 might alter cellular resistance to the DNA damage caused by radiation. Moreover, p53 is thought to function as a cell cycle checkpoint after irradiation, also suggesting that mutant p53 might change the cellular proliferative response to radiation. p53 mutations affect the cellular response to DNA damage, either by increasing DNA repair processes or, possibly, by increasing cellular tolerance to DNA damage. The association of p53 mutations with increased radioresistance suggests that alterations in the p53 gene might lead to oncogenic transformation. Current attractive model of carcinogenesis also showed that p53 gene is the major target of radiation. The majority of p53 mutations found so far is single base pairchanges (point mutations, which result in amino acid substitutionsor truncated forms of the P53 protein, and are widely distributedthroughout the evolutionarily conserved regions of the gene. Examination of p53 mutations in human cancer also shows an association between particular

  14. Protective Effect of Topically Applied Polypeptide from Chlamys farreri Against Ultraviolet Radiation-Induced Chronic Skin Damage in Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    迟明亮; 曹鹏利; 于国英; 朱莉; 王跃军; 王春波

    2003-01-01

    Polypeptide from Chlamys farreri (PCF) , a topical polypeptide isolated from Chlamys farreri, was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet-irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in the dorsal skin were determined using biochemical methods. The results showed:(1)PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration-dependent manner.(2)PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH-px.(3)The differences among the PCF groups and UV model group were significant (P<0.05, P<0.01). These results indicated that topical application of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

  15. Spinal Cord Injury

    Science.gov (United States)

    ... indicated by a total lack of sensory and motor function below the level of injury. People who survive a spinal cord injury will most likely have medical complications such as chronic pain and bladder and bowel ...

  16. What Are Sports Injuries?

    Science.gov (United States)

    ... 06:02 Size: 11.7 MB November 2014 What Are Sports Injuries? Fast Facts: An Easy-to- ... Research Is Being Done on Treating Sports Injuries? What’s the Difference Between an Acute and a Chronic ...

  17. Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

    Directory of Open Access Journals (Sweden)

    Sripathi M Sureban

    Full Text Available 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.

  18. Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

    Science.gov (United States)

    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.

  19. Disrupted Saccade Control in Chronic Cerebral Injury: Upper Motor Neuron-Like Disinhibition in the Ocular Motor System

    Science.gov (United States)

    Rizzo, John-Ross; Hudson, Todd E.; Abdou, Andrew; Lui, Yvonne W.; Rucker, Janet C.; Raghavan, Preeti; Landy, Michael S.

    2017-01-01

    Saccades rapidly direct the line of sight to targets of interest to make use of the high acuity foveal region of the retina. These fast eye movements are instrumental for scanning visual scenes, foveating targets, and, ultimately, serve to guide manual motor control, including eye–hand coordination. Cerebral injury has long been known to impair ocular motor control. Recently, it has been suggested that alterations in control may be useful as a marker for recovery. We measured eye movement control in a saccade task in subjects with chronic middle cerebral artery stroke with both cortical and substantial basal ganglia involvement and in healthy controls. Saccade latency distributions were bimodal, with an early peak at 60 ms (anticipatory saccades) and a later peak at 250 ms (regular saccades). Although the latencies corresponding to these peaks were the same in the two groups, there were clear differences in the size of the peaks. Classifying saccade latencies relative to the saccade “go signal” into anticipatory (latencies up to 80 ms), “early” (latencies between 80 and 160 ms), and “regular” types (latencies longer than 160 ms), stroke subjects displayed a disproportionate number of anticipatory saccades, whereas control subjects produced the majority of their saccades in the regular range. We suggest that this increase in the number of anticipatory saccade events may result from a disinhibition phenomenon that manifests as an impairment in the endogenous control of ocular motor events (saccades) and interleaved fixations. These preliminary findings may help shed light on the ocular motor deficits of neurodegenerative conditions, results that may be subclinical to an examiner, but clinically significant secondary to their functional implications. PMID:28184211

  20. Disrupted Saccade Control in Chronic Cerebral Injury: Upper Motor Neuron-Like Disinhibition in the Ocular Motor System.

    Science.gov (United States)

    Rizzo, John-Ross; Hudson, Todd E; Abdou, Andrew; Lui, Yvonne W; Rucker, Janet C; Raghavan, Preeti; Landy, Michael S

    2017-01-01

    Saccades rapidly direct the line of sight to targets of interest to make use of the high acuity foveal region of the retina. These fast eye movements are instrumental for scanning visual scenes, foveating targets, and, ultimately, serve to guide manual motor control, including eye-hand coordination. Cerebral injury has long been known to impair ocular motor control. Recently, it has been suggested that alterations in control may be useful as a marker for recovery. We measured eye movement control in a saccade task in subjects with chronic middle cerebral artery stroke with both cortical and substantial basal ganglia involvement and in healthy controls. Saccade latency distributions were bimodal, with an early peak at 60 ms (anticipatory saccades) and a later peak at 250 ms (regular saccades). Although the latencies corresponding to these peaks were the same in the two groups, there were clear differences in the size of the peaks. Classifying saccade latencies relative to the saccade "go signal" into anticipatory (latencies up to 80 ms), "early" (latencies between 80 and 160 ms), and "regular" types (latencies longer than 160 ms), stroke subjects displayed a disproportionate number of anticipatory saccades, whereas control subjects produced the majority of their saccades in the regular range. We suggest that this increase in the number of anticipatory saccade events may result from a disinhibition phenomenon that manifests as an impairment in the endogenous control of ocular motor events (saccades) and interleaved fixations. These preliminary findings may help shed light on the ocular motor deficits of neurodegenerative conditions, results that may be subclinical to an examiner, but clinically significant secondary to their functional implications.

  1. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems.

  2. The TGF-β/Smad repressor TG-interacting factor 1 (TGIF1 plays a role in radiation-induced intestinal injury independently of a Smad signaling pathway.

    Directory of Open Access Journals (Sweden)

    Mohammad Hneino

    Full Text Available Despite advances in radiation delivery protocols, exposure of normal tissues during the course of radiation therapy remains a limiting factor of cancer treatment. If the canonical TGF-β/Smad pathway has been extensively studied and implicated in the development of radiation damage in various organs, the precise modalities of its activation following radiation exposure remain elusive. In the present study, we hypothesized that TGF-β1 signaling and target genes expression may depend on radiation-induced modifications in Smad transcriptional co-repressors/inhibitors expressions (TGIF1, SnoN, Ski and Smad7. In endothelial cells (HUVECs and in a model of experimental radiation enteropathy in mice, radiation exposure increases expression of TGF-β/Smad pathway and of its target gene PAI-1, together with the overexpression of Smad co-repressor TGIF1. In mice, TGIF1 deficiency is not associated with changes in the expression of radiation-induced TGF-β pathway-related transcripts following localized small intestinal irradiation. In HUVECs, TGIF1 overexpression or silencing has no influence either on the radiation-induced Smad activation or the Smad3-dependent PAI-1 overexpression. However, TGIF1 genetic deficiency sensitizes mice to radiation-induced intestinal damage after total body or localized small intestinal radiation exposure, demonstrating that TGIF1 plays a role in radiation-induced intestinal injury. In conclusion, the TGF-β/Smad co-repressor TGIF1 plays a role in radiation-induced normal tissue damage by a Smad-independent mechanism.

  3. Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.

    Science.gov (United States)

    Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef

    2014-09-01

    Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (PTramadol increased the PWT by 336% in CCI rats (PTramadol increased the time spent on the open arms of CCI rats by 67% (PTramadol reduced the immobility time in CCI rats by 22% (PTramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP.

  4. The role of Tc-99m HMPAO brain perfusion SPECT in the psychiatric disability evaluation of patients with chronic traumatic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    So, Young [Nuclear Medicne, Seoul National Univ., Seoul (Korea, Republic of); Lee, Kang Wook; Lee, Sun Woo; Ghi, Lek Sung; Song, Chang June [College of Medicine, Chungnam National Univ., Taejon (Korea, Republic of)

    2002-08-01

    We studied whether brain perfusion SPECT is useful in the psychiatric disability evaluation of patients with chronic traumatic brain injury (TBI). Sixty-nine patients (M:F=58:11, age 39 {+-} 14 years) who underwent Tc-99m HMPAO brain SPECT, brain MRI and neuropsychological (NP) tests during hospitalization in psychiatric wards for the psychiatric disability evaluation were included; the severity of injury was mild in 31, moderate in 17 and severe in 21. SPECT, MRI, NP tests were performed 6 {approx} 61 months (mean 23 months) post-injury. Diagnostic accuracy of SPECT and MRI to show hypoperfusion or abnormal signal intensity in patients with cognitive impairment represented by NP test results were compared. Forty-two patients were considered to have cognitive impairment on NP tests and 27 not. Brain SPECT showed 71% sensitivity and 85% specificity, while brain MRI showed 62% sensitivity and 93% specificity (p>0.05, McNemar test). SPECT found more cortical lesions and MRI was superior in detecting white matter lesions. sensitivity and specificity of 31 mild TBI patients were 45%, 90% for SPECT and 27%, 100% for MRI (p>0.05, McNemar test). Among 41 patients with normal brain MRI, SEPCT showed 63% sensitivity (50% for mild TBI) and 88% specificity (85% for malingerers). Brain SPECT has a supplementary role to neuropsychological tests in the psychiatric disability evaluation of chronic TBI patients by detecting more cortical lesions than MRI.

  5. Prevention of liver fibrosis by intrasplenic injection of high-density cultured bone marrow cells in a rat chronic liver injury model.

    Directory of Open Access Journals (Sweden)

    Jie Lian

    Full Text Available Endothelial progenitor cells (EPCs from bone marrow have proven to be functional for the prevention of liver fibrosis in chronic liver injury. However, expansion of EPCs in culture is complicated and expansive. Previously, we have established a simple method that could enrich and expand EPCs by simple seeding bone marrow cells in high density dots. The purpose of this study is to evaluate whether cells derived from high-density (HD culture of rat bone marrow cells could prevent the liver fibrosis in a chronic liver injury rat model, induced by carbon tetrachloride (CCl4. Flow cytometric analysis showed that cells from HD culture were enriched for EPCs, expressing high levels of EPC markers. Intrasplenic injection of HD cultured bone marrow cells in the CCl4-induced liver injury rat showed an enhanced antifibrogenic effect compared with animals treated with cells from regular-density culture. The antifibrogenic effect was demonstrated by biochemical and histological analysis 4 weeks post-transplantation. Furthermore, cells from HD culture likely worked through increasing neovascularization, stimulating liver cell proliferation, and suppressing pro-fibrogenic factor expression. HD culture, which is a simple and cost-effective procedure, could potentially be used to expand bone marrow cells for the treatment of liver fibrosis.

  6. Assessing the Impact of Post Traumatic Stress Symptoms on Resting State Function Networks in a Military Chronic Mild Traumatic Brain Injury Sample.

    Science.gov (United States)

    Nathan, Dominic E; Bellgowan, Julie F; French, Louis M; Wolf, Jonathan P; Oakes, Terry; Mielke, Jeannine B; Sham, Elyssa B; Liu, Wei; Riedy, Gerard

    2017-03-19

    The relationship between post traumatic stress disorder (PTSD) and chronic symptoms of mild traumatic brain injury (mTBI) is difficult to discern and poorly understood. An accurate differential diagnosis, assessment and treatment of mTBI and PTSD is challenging due to significant symptom overlap and the absence of clearly established biomarkers. The objective of this work is to examine how post traumatic stress influences task-free brain networks in chronic mTBI subjects. Control subjects (N=44) were compared with chronic mTBI subjects with low (N=58, PCLC totalpost traumatic stress symptoms (PTSS). The results indicate significant differences in Brodmann area 10 for all mTBI subject groups, indicating potential mTBI related disruptions with regulation of emotions and decision-making. The effects of PTSS were observed in the anterior cingulate, and parahippocampus suggesting possible disruptions pertaining to memory regulation, encoding and retrieval. The overall results indicate the presence of aberrant connectivity patterns between controls and chronic mTBI subjects with low, medium and high PTSS. Furthermore, the findings suggest a disruption in attention relating to a network of brain regions involved with emotional regulation and memory coding, rather than a fear related response. Taken together, the results suggest these regions form a network that could be a target for future research pertaining to PTSD and chronic mTBI. Furthermore, the use of clinical measures, task based imaging studies or multimodal imaging could help further elucidate specific neural correlates of PTSS and mTBI.

  7. Action spectrum and mechanisms of UV radiation-induced injury in lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Audette-Stuart, M., E-mail: stuartm@aecl.ca [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada); Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S. [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada)

    2011-06-15

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: > Frogs were collected from background and higher tritium level habitats. > The micronucleus assay was conducted on liver cells obtained from the frogs. > No detrimental effects were noted in frogs exposed to elevated tritium. > Adaptive responses were observed in frogs exposed to elevated tritium.

  9. The ameliorative effects of exercise on cognitive impairment and white matter injury from blood-brain barrier disruption induced by chronic cerebral hypoperfusion in adolescent rats.

    Science.gov (United States)

    Lee, Jae-Min; Park, Jong-Min; Song, Min Kyung; Oh, Yoo Joung; Kim, Chang-Ju; Kim, Youn-Jung

    2017-01-18

    Vascular dementia is the progressive change in blood vessels that leads to neuronal injuries in vulnerable areas induced by chronic cerebral hypoperfusion (CCH). CCH induces disruption of blood-brain barrier (BBB), and this BBB disruption can initiate the cognitive impairment and white matter injury. In the present study, we evaluated the effect of treadmill exercise on the cognitive impairment, white matter injury, and BBB disruption induced by CCH. Vascular dementia was induced by permanent bilateral common carotid arteries occlusion (BCCAO) in rats. The rats in the exercise group were made to run on a treadmill for 30min once a day for 14 weeks, starting 4 weeks after birth. Our results revealed that treadmill exercise group was alleviated the cognitive impairment and myelin degradation induced by CCH. The disruption of BBB after CCH indicates degradation of occludin, zonula occluden-1 (ZO-1), and up-regulation of matrix metalloproteinases (MMPs). Treadmill exercise may provide protective effects on BBB disruption from degradation of occludin, ZO-1, and overexpression of MMP-9 after CCH. These findings suggest that treadmill exercise ameliorates cognitive impairment and white matter injury from BBB disruption induced by CCH in rats. The present study will be valuable for means of prophylactic and therapeutic intervention for patients with CCH.

  10. The Role of e-NOS in Chronic Cholestasis-Induced Liver and Renal Injury in Rats: The Effect of N-Acetyl Cysteine

    Directory of Open Access Journals (Sweden)

    Yusuf Gunay

    2014-01-01

    Full Text Available Introduction. The role of chronic cholestasis (CC in liver injury and fibrosis remains unclear. The aims of this study were to define the role of endothelial nitric oxide synthase (e-NOS in CC and the protective effect of N-acetyl-L-cysteine (NAC in liver and kidney injury. Materials and Methods. Group A (sham group; Group B (CBDL; and Group C (CBDL + NAC. Group C received daily dosage of NAC (100 mg/kg intraperitoneally for up to 4 weeks. Results. The rate of bridging fibrosis was higher (100% versus 20%, P=.025, but the intensity of e-NOS in liver was lower in rats that received NAC (1.3 versus 2.7, P=.046. The necrotic area in the kidneys among rats that received NAC was lower at week 4 (48% versus 57%; P<.001. The numbers of e-NOS stained cells in kidney were similar in sham group and the two groups with CBDL. Discussion. NAC reduced the stimulus for liver fibrosis in this rat model of CC and attenuated liver and kidney injury. Our study showed that e-NOS expression increased in liver tissue of rats with CC and that this was reversed by NAC. Treatment with NAC might restore e-NOS protein expression and prevent liver injury in CC.

  11. [Comparative evaluation of influence of low-intensity laser radiation of different spectrum components and regimen of laser work upon microcirculation in comprehensive treatment of chronic parodontitis].

    Science.gov (United States)

    Krechina, E K; Shidova, A V; Maslova, V V

    2008-01-01

    Comparative study of the influence details of low-intensity pulse and continuous oscillation of laser radiation of red and infrared parts of spectrum upon microcirculation indices in comprehensive treatment of chronic parodontitis of light and middle severity was performed. For the first time the predominantly activating influence upon microcirculation in gingival tissues of the pulsed laser radiation in the red part of spectrum was established.

  12. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Haytham [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Galal, Omima [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Abdelrahim, Eman [Department of Medical Histology, Qena Faculty of Medicine, South Valley University (Egypt); Ono, Yusuke [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Mostafa, Emtethal [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Li, Tao-Sheng, E-mail: litaoshe@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    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.

  13. Age-specific radiation dose commitment factors for a one-year chronic intake

    Energy Technology Data Exchange (ETDEWEB)

    Hoenes, G.R.; Soldat, J.K.

    1977-11-01

    During the licensing process for nuclear facilities, radiation doses and dose commitments must be calculated for people in the environs of a nuclear facility. These radiation doses are determined by examining characteristics of population groups, pathways to people, and radionuclides found in those pathways. The pertinent characteristics, which are important in the sense of contributing a significant portion of the total dose, must then be analyzed in depth. Dose factors are generally available for adults, see Reference 1 for example, however numerous improvements in data on decay schemes and half-lives have been made in recent years. In addition, it is advisable to define parameters for calculation of the radiation dose for ages other than adults since the population surrounding nuclear facilities will be composed of various age groups. Further, since infants, children, and teens may have higher rates of intake per unit body mass, it is conceivable that the maximally exposed individual may not be an adult. Thus, it was necessary to develop new radiation-dose commitment factors for various age groups. Dose commitment factors presented in this report have been calculated for a 50-year time period for four age groups.

  14. Adult Lysophosphatidic Acid Receptor 1-Deficient Rats with Hyperoxia-Induced Neonatal Chronic Lung Disease Are Protected against Lipopolysaccharide-Induced Acute Lung Injury

    Science.gov (United States)

    Chen, Xueyu; Walther, Frans J.; Laghmani, El H.; Hoogeboom, Annemarie M.; Hogen-Esch, Anne C. B.; van Ark, Ingrid; Folkerts, Gert; Wagenaar, Gerry T. M.

    2017-01-01

    Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air. After 7 weeks, male rats received either LPS (2 mg kg−1) or 0.9% NaCl by intraperitoneal injection. Alveolar development and lung inflammation were investigated by morphometric analysis, IL-6 production, and mRNA expression of cytokines, chemokines, coagulation factors, and an indicator of oxidative stress. Results: LPAR1-deficient and control rats developed hyperoxia-induced neonatal emphysema, which persisted into adulthood, as demonstrated by alveolar enlargement and decreased vessel density. LPAR1-deficiency protected against LPS-induced lung injury. Adult controls with BPD exhibited an exacerbated response toward LPS with an increased expression of pro-inflammatory mRNAs, whereas LPAR1-deficient rats with BPD were less sensitive to this “second hit” with a decreased pulmonary influx of macrophages and neutrophils, interleukin-6 (IL-6) production, and mRNA expression of IL-6, monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant 1, plasminogen activator inhibitor-1, and tissue factor. Conclusion: LPAR1-deficient rats have increased hyperoxia-induced BPD survival rates and, despite the presence of neonatal emphysema, are less sensitive to an aggravated “second hit” than Wistar controls with BPD. Intervening in LPA-LPAR1-dependent signaling may not only have therapeutic potential for neonatal chronic

  15. Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Matthew S. [Department of Physics and Astronomy, Western University, London, Ontario, N6A 3K7, Canada and Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Ouriadov, Alexei; Hegarty, Elaine [Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Thind, Kundan [Department of Medical Biophysics, Western University, London, Ontario, N6A 5C1, Canada and Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Wong, Eugene [Department of Physics and Astronomy, Western University, London, Ontario, N6A 3K7, Canada and London Regional Cancer Program, London, Ontario, N6C 2R6 (Canada); Hope, Andrew [Department of Radiation Oncology, University of Toronto, Toronto, Ontario, M5S 3E2, Canada and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, M5T 2M9 (Canada); Santyr, Giles E., E-mail: gsantyr@robarts.ca [Department of Medical Biophysics, Western University, London, Ontario, N6A 5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Department of Medical Imaging, Western University, London, Ontario, N6A 5B7 (Canada)

    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

  16. Adiponectin protects rat myocardium against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Wenxiao Ding

    Full Text Available Obstructive sleep apnea syndrome (OSAS is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5-6% for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05. However, when adiponectin (Ad was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05. To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL analysis. It was showed that the apoptosis percentage in CIH group (2.948% was significantly higher than that in NC group (0.4167% and CIH + Ad group (1.219% (p<0.05. Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05. Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH

  17. Adiponectin protects the genioglossus of rats against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-feng; HUANG Han-peng; DING Wen-xiao; DING Ning; LU Gan; LIU Jian-nan; ZHANG Xi-long

    2013-01-01

    Background Obstructive sleep apnea hypopnea syndrome,characterized by chronic intermittent hypoxia (CIH),is closely correlated with genioglossus dysfunction.CIH has been identified to mediate mitochondrial damage in genioglossus.It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction.This study aimed to investigate the role of ERS in CIH-induced genioglossus injury,as well as the possible intervention effect of adiponectin (Ad) supplement in rats.Methods Forty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A,n=15) as a control or CIH (groups B and C,n=15,respectively).Throughout the exposure period,intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B.After 35-day exposure,genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection,following blood sampling.Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus.Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA).Results Significant hypoadiponectinemia was revealed in group B only (P <0.05).Compared to those in groups A and C,expressions of markers involved in ERS,such as glucose regulated protein 78 (GRP78),p-PERK,phosphorylated eukaryotic initiation factor 2α (p-elF2α),phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α),spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6),were significantly enhanced in group B (all P <0.01); while no significant difference was shown between groups A and C (all P >0.05).ERS-associated apoptotic pathways were remarkably activated in group B.The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP),B-cell lymphoma/leukemia associatied X protein (BAX)and caspase-12 were

  18. Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung

    Energy Technology Data Exchange (ETDEWEB)

    Siva, Shankar, E-mail: shankar.siva@petermac.org [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville (Australia); Hardcastle, Nicholas [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne (Australia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong (Australia); Kron, Tomas [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne (Australia); Bressel, Mathias [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne (Australia); Callahan, Jason [Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); MacManus, Michael P.; Shaw, Mark; Plumridge, Nikki [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hicks, Rodney J. [Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Medicine, University of Melbourne, Parkville (Australia); Steinfort, Daniel [Department of Medicine, University of Melbourne, Parkville (Australia); Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne (Australia); Ball, David L. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hofman, Michael S. [Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Medicine, University of Melbourne, Parkville (Australia)

    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

  19. SU-E-J-247: Time Evolution of Radiation-Induced Lung Injury After Stereotactic Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Grassberger, C; Sharp, G; Fintelmann, F; Paganetti, H; Willers, H [Massachusetts General Hospital, Boston, MA (United States)

    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.

  20. Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

    Science.gov (United States)

    Kimura, Yoshiyuki; Sumiyoshi, Maho; Kobayashi, Toshiya

    2014-01-01

    Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

  1. Acoustic Radiation Force Impulse Elastography for fibrosis evaluation in patients with chronic hepatitis C: An international multicenter study

    Energy Technology Data Exchange (ETDEWEB)

    Sporea, Ioan, E-mail: isporea@umft.ro [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Bota, Simona, E-mail: bota_simona1982@yahoo.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Peck-Radosavljevic, Markus, E-mail: markus.peck@meduniwien.ac.at [Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Sirli, Roxana, E-mail: roxanasirli@gmail.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Tanaka, Hironori, E-mail: hironori@hyo-med.ac.jp [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Iijima, Hiroko, E-mail: hiroko.iijima@nifty.com [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Badea, Radu, E-mail: rbadea2003@yahoo.com [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Lupsor, Monica, E-mail: monica.lupsor@umfcluj.ro [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Fierbinteanu-Braticevici, Carmen, E-mail: cfierbinteanu@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Petrisor, Ana, E-mail: ana1petrisor@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Saito, Hidetsugu, E-mail: hidetsugusaito@gmail.com [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Ebinuma, Hirotoshi, E-mail: ebinuma@a5.keio.jp [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Friedrich-Rust, Mireen, E-mail: Mireen.Friedrich-Rust@kgu.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); Sarrazin, Christoph, E-mail: sarrazin@em.uni-frankfurt.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); and others

    2012-12-15

    Aim: The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C. Patients and methods: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5–10 valid measurements, expressed in meters/second – m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6–10 valid measurements, expressed in kiloPascals – kPa). Results: Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r = 0.654) was found between ARFI measurements and fibrosis (p < 0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 – cut-off > 1.19 m/s (AUROC = 0.779), F ≥ 2 – cut-off > 1.33 m/s (AUROC = 0.792), F ≥ 3 – cut-off > 1.43 m/s (AUROC = 0.829), F = 4 – cut-off > 1.55 m/s (AUROC = 0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r = 0.728 vs. 0.689, p = 0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p = 0.01) and fibrosis (F ≥ 1, METAVIR) (p = 0.01). Conclusion: ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients.

  2. Brainstem white matter integrity is related to loss of consciousness and postconcussive symptomatology in veterans with chronic mild to moderate traumatic brain injury.

    Science.gov (United States)

    Delano-Wood, L; Bangen, K J; Sorg, S F; Clark, A L; Schiehser, D M; Luc, N; Bondi, M W; Werhane, M; Kim, R T; Bigler, E D

    2015-09-01

    We investigated associations between DTI indices of three brainstem white matter tracts, traumatic brain injury (TBI) injury characteristics, and postconcussive symptomatology (PCS) in a well-characterized sample of veterans with history of mild to moderate TBI (mTBI). 58 military veterans (mTBI: n = 38, mean age = 33.2, mean time since injury = 90.9 months; military controls [MC]; n = 20; mean age = 29.4) were administered 3T DTI scans as well as a comprehensive neuropsychiatric evaluation including evaluation of TBI injury characteristics and PCS symptoms (e.g., negative mood, dizziness, balance and coordination difficulties). Tractography was employed by seeding ROIs along 3 brainstem white matter tracts (i.e., medial lemniscus-central tegmentum tract [ML-CTT]; corticospinal tracts [CST], and pontine tegmentum [PT]), and mean DTI values were derived from fractional anisotropic (FA) maps. Results showed that there were no significant difference in FA between the MC and TBI groups across the 3 regions of interest; however, among the TBI group, CST FA was significantly negatively associated with LOC duration. Additionally, lower FA of certain tracts-most especially the PT-was significantly associated with increased PCS symptoms (i.e., more severe vestibular symptoms, poorer physical functioning, and greater levels of fatigue), even after adjusting for PTSD symptoms. Our findings show that, in our sample of veterans with mTBI, tractography-based DTI indices of brainstem white matter tracts of interest are related to the presence and severity of PCS symptoms. Findings are promising as they show linkages between brainstem white matter integrity and injury severity (LOC), and they raise the possibility that the pontine tegmentum in particular may be a useful marker of PCS symptoms. Collectively, these data point to important neurobiological substrates of the chronic and complex constellation of symptoms following the 'signature injury' of our

  3. Biochemical Changes in Saliva of Patients with Chronic Generalized Parodontitis under Combined Action of Alternating Running Magnetic Field and Laser Radiation

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    O.Yu. Guseva

    2009-09-01

    Full Text Available Biochemical changes in oral fluid of patients with chronic generalized parodontitis were investigated; the most informative indices were found out, they were used for estimating complex therapy effectiveness by means of low intensive helium — neon laser radiation and alternating running magnetic field

  4. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.

    Science.gov (United States)

    Yentrapalli, Ramesh; Azimzadeh, Omid; Sriharshan, Arundhathi; Malinowsky, Katharina; Merl, Juliane; Wojcik, Andrzej; Harms-Ringdahl, Mats; Atkinson, Michael J; Becker, Karl-Friedrich; Haghdoost, Siamak; Tapio, Soile

    2013-01-01

    The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal) and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.

  5. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.

    Directory of Open Access Journals (Sweden)

    Ramesh Yentrapalli

    Full Text Available The etiology of radiation-induced cardiovascular disease (CVD after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h causes human umbilical vein endothelial cells (HUVECs to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.

  6. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

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    Olga Loseva

    2014-07-01

    Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

  7. Case of chronic progressive radiation myelopathy with a CT myelogram simulating intramedullary tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kanemaru, Kazutomi; Kamo, Hisaki; Yamao, Satoshi; Akiguchi, Ichiro; Kameyama, Masakuni

    1985-05-01

    A 58-year-old man underwent a right middle lobectomy in June, 1975, for poorly differentiated adenocarcinoma of the lung. Postoperative irradiation was given to the hilus (6100 rads), and to the right supraclavicular area (6000 rads). In 1980, 60 months after completion of irradiation, the patient noticed weakness of his legs particularly on the left side. In 1982, he noticed the girdle sensation in the upper thoracic region, and paresthesia in the lateral side of the right thigh. In Dec 1983, micturition disturbance appeared, and gait disturbance progressed, he was admitted to the Kyoto University Hospital. Neurological examination revealed an incomplete left Brown-Sequard syndrome with diminution of pain and thermal sensation on the right lower limb, and weakness and spasticity particularly on the left lower limb. Conventional myelogram with CT myelogram showed spinal cord swelling from T-2 through T-5. No extramedullary lesion was found. Laminectomy was performed through T-1 to T-6. When the dura was opened, the cord was swollen and necrotic with a cyst formation. Microscopic examination of the thickened part of the cord showed necrosis and gliosis. The lesion was correspond to the cord segments exposed to the radiation, and a diagnosis of radiation myelopathy was made. Several cases of radiation myelopathy with definite swelling of the cord at myelography were reported, but myelography in these cases was performed at most within 11 months after the onset. In this case, myelography was performed three years after the onset, and revealed difinite swelling of the cord due to a cyst formation. (author).

  8. Impact of a limited trial of walking training using body weight support and a treadmill on the gait characteristics of an individual with chronic, incomplete spinal cord injury.

    Science.gov (United States)

    Leahy, Theresa E

    2010-10-01

    Studies showing improvement in locomotor ability for individuals with chronic spinal cord injury (SCI) use training times that may be prohibitive for clinics. The purpose of this study was to examine the impact of a limited period of training on the gait characteristics of a man with chronic, incomplete SCI. The participant was a minimally ambulatory 59-year-old man almost 3 years post C(3) central cord injury with an ASIA Impairment Scale (AIS) classification of C. The participant received 11 training sessions using body weight support and a treadmill (BWST) over a 6-week period. The Six Minute Walk Test (6 MWT), and gait characteristics measured with motion analysis were obtained pretraining and posttraining. The participant made improvements on all measured gait characteristics. The participant's walking speed and comfort level on the treadmill improved enough for him to use community resources. This participant was able to make improvements in his gait with a much shorter training time period than those reported in previous locomotor training studies. Although this man did not obtain community ambulation status, his decreased dependence on his power chair at home and his new ability to use an available treadmill allow for continued walking practice outside the clinic.

  9. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury

    OpenAIRE

    Radouil Tzekov; Clint Dawson; Megan Orlando; Benoit Mouzon; Jon Reed; James Evans; Gogce Crynen; Michael Mullan; Fiona Crawford

    2016-01-01

    Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue w...

  10. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  11. Search and Neutralize Factors (Cspgs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

    Science.gov (United States)

    2014-04-01

    clinically relevant treatment to facilitate recovery after SCI. During the 6-moths of no-cost extension we have completed post - mortem immunochemistry... lesions during the recordings. Methods. Spinal cord injury. All procedures were performed on adult, female Sprague-Dawley rats (~210 g) in compliance... post -operative pain. Contusion injury was performed at T10 spinal level using computer controlled IH-0400 Impactor device (Precision System and

  12. Impact of chronic, low-level ionising radiation exposure on terrestrial invertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Hingston, J.; Wood, M.D.; Copplestone, D.; Zinger, I. [Liverpool Univ., School of Biological Sciences, Merseyside (United Kingdom)

    2004-07-01

    There is a need to confirm that the environment is being adequately protected from the mixture of contaminants released into it. In the field of environmental radioactivity, tools have been developed to assess the impacts of ionising radiation on wildlife. The scientific data upon which these assessments are based is, however, lacking. New documentation has been produced by the UK Environment Agency to provide guidelines on structuring experiments (using environmentally relevant doses) and select suitable non-human species and endpoints for study. It is anticipated that this documentation will be used to direct future experiments in this field. This paper presents the results of the first of these experiments. Numbers of the earthworm Eisenia fetida and the wood louse Porcellio scaber were segregated and constantly exposed to one of six radiation doses (background, 0.1, 0.4, 1.5, 4.0 and 8.0 mGyh{sup -1}) for a total of 16 and 14 weeks respectively. The endpoints of mortality, number of viable offspring and average weight of an individual were recorded and the results of this study will be discussed here. (author)

  13. Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

    Directory of Open Access Journals (Sweden)

    W. Lu

    Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

  14. Novel epigallocatechin-3-gallate (EGCG derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice.

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    Xavier Xifró

    Full Text Available Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI. First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi. We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p. during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN, a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.

  15. Ameliorative potential of Butea monosperma on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

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    Venkata R.K. Thiagarajan

    2012-12-01

    Full Text Available The present study was designed to investigate the ameliorative role of ethanolic extract from leaves of Butea monosperma in chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia & allodynia in the left hind paw and tail thermal hyperalgesia. Further on, thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of Butea monosperma leaves and pregabalin (serving as positive control were administered for 14 consecutive days starting from the day of surgery. CCI resulted in significant changes in behavioural and biochemical parameters. Pretreatment of Butea monosperma attenuated CCI induced development of behavioural, biochemical and histopathological alterations in a dose dependent manner, which is comparable to that of pregabalin pretreated group. These findings may be attributed to its potential anti-oxidative, neuroprotective and calcium channel modulatory actions of Butea monosperma.O presente trabalho visou investigar o papel do extrato etanólico de folhas de Butea monosperma no alívio da dor neuropática pela injúria de constrição crônica (CCI do nervo ciático induzida em ratos. Placa quente, gota de acetona, pressão na pata, testes de imersão de pelo e cauda de Von Frey foram utilizados para acessar o grau de hiperalgesia térmica, alodinia química fria, hiperalgesia mecânica e alodinia na pata trazeira esquerda e hiperalgesia térmica da cauda. Além disso, substâncias reativas com ácido tiobarbitúrico (TBARS, glutatião reduzido (GSH e níveis de cálcio total foram estimados para acessar as altera

  16. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, P.R. Vivek, E-mail: prvkumar06@gmail.com [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Seshadri, M. [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Jaikrishan, G. [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Das, Birajalaxmi [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2015-05-15

    Highlights: • Effect of chronic low dose natural radiation in radio adaptive response studied. • PBMCs of subjects from NLNRA and HLNRA were challenged with gamma radiation. • DNA damage and repair in PBMCs was compared using the alkaline comet assay. • Significant reduction in DNA damage in subjects of high dose group from HLNRA noted. • Probable induction of an in vivo radio adaptive response in subjects from HLNRA. - Abstract: This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year{sup −1}), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N = 43, range 1.07 mSv year{sup −1} to 5.55 mSv year{sup −1}) and 9.62 mSv (N = 34, range 6.07 mSv year{sup −1} to17.41 mSv year{sup −1}), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P = 0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from

  17. Solid cancer mortality associated with chronic external radiation exposure at the French atomic energy commission and nuclear fuel company.

    Science.gov (United States)

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2011-07-01

    nuclear workers, which should improve knowledge about the risks associated with chronic low doses and provide useful risk estimates for radiation protection.

  18. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely radiating lumbar back pain

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, E.M.

    1984-01-01

    After surgery necessitated by lumbar back pain syndromes, radiolucency verified by CT may appear in the sacrospinal muscle group on the operate side. This radiolucency represents muscular atrophy and is in its most severe form a result of the replacement of muscle tissue with adipose tissue. Such muscular atrophy appeared in the present series in 31 out of all 156 patients (19.9%) and in 29 out of 94 patients operated on because of radiating lumbar back pain (30.9%). The radiological appearance, extent, and HU values of this muscular atrophy are presented in detail. Only weak correlations with the multitude of clinical symptoms and signs were found in this retrospective study. The effects of irreversible muscular atrophy on the indications for surgery and physiotherapy are discussed.

  19. A pilot trial to examine the association between circulating endothelial cell levels and vascular injury in patients with diabetes and chronic kidney disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Shayan Shirazian

    2016-03-01

    Full Text Available Objective While albuminuria is a marker for progressive chronic kidney disease (CKD in patients with type 2 diabetes (T2DM, both albuminuric and normoalbuminuric patients appear prone to vascular injury. This pilot study examines the association between circulating endothelial cell (CEC levels and vascular injury in patients with T2DM and CKD. Methods In this cross-sectional study, eligible adult patients had T2DM, and stage 3 CKD (estimated glomerular filtration rate between 30 and 60 mL/min/1.73m2. CEC levels were tested by Janssen Diagnostics, LLC using an immuno-magnetic bead-based assay. CEC levels were compared to levels in a previously tested normal population. Correlations between CEC levels and other vascular injury markers (urine albumin, von-Willebrand factor antigen, hs-CRP, uric acid were performed. Results Patients included 40 adults of which nineteen were normoalbuminuric.  Mean CEC levels (38.7, SD 38.1 cells were significantly higher than the normal population (M = 21±18 cells, p<0.001; N = 249, including in the normoalbuminuric subgroup (M = 42.9±42.5 cells, p<0.001. CEC levels were significantly correlated with uric acid levels (r=0.33, p=0.039. Conclusions CEC levels in patients with T2DM and CKD, both albuminuric and normoalbuminuric, are significantly higher than a normal population, suggesting the presence of vascular injury in both groups. Future studies are needed to evaluate the role of CECs as a biomarker to predict outcomes in normoalbuminuric patients with CKD.

  20. Repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus after traumatic brain injury: a case study.

    Science.gov (United States)

    Kreuzer, Peter Michael; Landgrebe, Michael; Frank, Elmar; Langguth, Berthold

    2013-01-01

    Tinnitus is a frequent symptom of traumatic brain injury, which is difficult to treat. Repetitive transcranial magnetic stimulation has shown beneficial effects in some forms of tinnitus. However, traumatic brain injury in the past has been considered as a relative contraindication for repetitive transcranial magnetic stimulation because of the increased risk of seizures. Here we present the case of a 53-year-old male patient suffering from severe tinnitus after traumatic brain injury with comorbid depression and alcohol abuse, who received 5 treatment series of repetitive transcranial magnetic stimulation (1 Hz stimulation protocol over left primary auditory cortex, 10 sessions of 2000 stimuli each, stimulation intensity 110% resting motor threshold). Repetitive transcranial magnetic stimulation was tolerated without any side effects and tinnitus complaints (measured by a validated tinnitus questionnaire and numeric rating scales) were improved in a replicable way throughout 5 courses of transcranial magnetic stimulation up to now.

  1. Genetic effects in somatic and germ cells, induced by ionizing radiations

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, B.; Benova, D.; Bajrakova, A.; Bulanova, M.; Vyglenov, A.; Rupova, I.; Georgieva, I. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1983-01-01

    Quantitative data are reported on injuries to hereditary structures in somatic and sex cells, induced by different types of ionizing radiation. The model systems used were human peripheral blood lymphocytes, in vitro irradiated with different doses: bone-marrow cells of mice and rats irradiated in vivo: mouse, rat, rabbit and hamster sex cells. To evaluate the dose-effect dependency after acute and chronic irradiation, the authors used mathematical models, describing the amount of chromosomal injuries. Attempt was made to estimate the somatic and genetic risk, following acute and chronic irradiation with different doses of ionizing radiations.

  2. ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Juliana Ayres de Alencar Arrais GUERRA

    2015-09-01

    Full Text Available BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

  3. Modeling deterministic effects in hematopoietic system caused by chronic exposure to ionizing radiation in large human cohorts.

    Science.gov (United States)

    Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akleyev, Alexander V; Yashin, Anatoly I

    2010-09-01

    A new model of the hematopoietic system for humans chronically exposed to ionizing radiation allows for quantitative description of the initial hematopoiesis inhibition and subsequent increase in the risks of late stochastic effects such as leukemia. This model describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the three blood cell types (leukocytes, erythrocytes, and platelets). The model parameters are estimated from the results of other experiments. They include the steady-state numbers of hematopoietic stem cells and peripheral blood cell lines for an unexposed organism, amplification parameters for each blood cell line, parameters describing the proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity in respect to cell death and non-lethal cell damages. The dynamic model of hematopoiesis is applied to the data on a subcohort of the Techa River residents with hematological measurements (e.g., blood counts) performed in 1950-1956 (which totals to about 3,500 exposed individuals). Among well-described effects observed in these data are the slope values of the dose-effect curves describing the hematopoietic inhibition and the dose rate patterns of the fractions of cytopenic states (e.g., leukopenia, thrombocytopenia). The model has been further generalized by inclusion of the component describing the risk of late stochastic effects. The risks of the development of late effects (such as leukemia) in population groups with specific patterns of early reactions in hematopoiesis (such as leukopenia induced by ionizing radiation) are investigated using simulation studies and compared to data.

  4. Surgical treatment of acute and chronic anterior and posterior cruciate ligament and lateral side injuries of the knee.

    Science.gov (United States)

    Levy, Bruce A; Boyd, Joel L; Stuart, Michael J

    2011-06-01

    Combined anterior cruciate ligament, posterior cruciate ligament, and lateral-sided injuries of the knee most often occurs secondary to a forced varus moment or after knee dislocation. Management controversies include the optimal timing of surgery, operative techniques, and postoperative rehabilitation. Recent systematic literature reviews have demonstrated higher rates of failure with repair of the lateral and posterolateral corner structures, as opposed to reconstruction. However, the ideal ligament reconstruction techniques remain unclear. This chapter will review the combined anterior cruciate ligament/posterior cruciate ligament/lateral-sided injury pattern, including the physical examination findings, imaging, timing of surgery, graft selection, operative techniques, and postoperative rehabilitation protocols.

  5. Self-sustained motor activity triggered by interlimb reflexes in chronic spinal cord injury, evidence of functional ascending propriospinal pathways.

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    Penelope A McNulty

    Full Text Available The loss or reduction of supraspinal inputs after spinal cord injury provides a unique opportunity to examine the plasticity of neural pathways within the spinal cord. In a series of nine experiments on a patient, quadriplegic due to spinal cord injury, we investigated interlimb reflexes and self-sustained activity in completely paralyzed and paretic muscles due to a disinhibited propriospinal pathway. Electrical stimuli were delivered over the left common peroneal nerve at the fibular head as single stimuli or in trains at 2-100 Hz lasting 1 s. Single stimuli produced a robust interlimb reflex twitch in the contralateral thumb at a mean latency 69 ms, but no activity in other muscles. With stimulus trains the thumb twitch occurred at variable subharmonics of the stimulus rate, and strong self-sustained activity developed in the contralateral wrist extensors, outlasting both the stimuli and the thumb reflex by up to 20 s. Similar behavior was recorded in the ipsilateral wrist extensors and quadriceps femoris of both legs, but not in the contralateral thenar or peroneal muscles. The patient could not terminate the self-sustained activity voluntarily, but it was abolished on the left by attempted contractions of the paralyzed thumb muscles of the right hand. These responses depend on the functional integrity of an ascending propriospinal pathway, and highlight the plasticity of spinal circuitry following spinal cord injury. They emphasize the potential for pathways below the level of injury to generate movement, and the role of self-sustained reflex activity in the sequelae of spinal cord injury.

  6. Current understanding of radiation -induced gastroduodenal injury%放射性胃、十二指肠损伤的研究现状

    Institute of Scientific and Technical Information of China (English)

    魏华琳; 周平; 郭小陪

    2016-01-01

    随着放疗技术在腹部肿瘤的应用,胃、十二指肠放射性损伤越来越引起临床医生的重视。放射性胃、十二指肠损伤多出现在黏膜褶皱处及黏膜萎缩部位,实质是一个炎症过程。临床研究表明糖尿病、HP感染、肝硬化等既往史与损伤的发生有关,更多研究探讨了物理因素的临床预测价值。先进的放疗技术是否在胃肠损伤安全性方面更具备优势值得进一步探讨。治疗以减轻炎性、止血为主,严重的放射性胃肠出血的治疗棘手且方法不一。%With the development of the wide use of radiation therapy in abdominal tumor,doctors pay more attention to the gastroduodenal radioactive injury.Radiation stomach and duodenal injury occurs in the mucosal folds and mu-cous membrane atrophy site,which is an inflammatory process in essence.Clinical studies have indicated that the his-tory of diabetes,HP infection,liver cirrhosis and other diseases are related to the occurrence of damage.There have been more researches about the clinical value of physical factors.Whether advanced radiotherapy technology has more advantages in the safety of gastrointestinal injury needs further study.Treatment is to reduce the inflammatory,bleed-ing.The treatment of severe radiation gastrointestinal bleeding is difficult.

  7. Changes and significance of occludin expression in rats with blood-brain barrier injury induced by microwave radiation

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    Xiang LI

    2011-07-01

    Full Text Available Objective To observe the changes in occludin expression in hippocampus of rats injured by long-term microwave exposure at low dosage,and explore the mechanism of the effect of occludin on microwave-induced blood-brain barrier(BBB injury.Methods A total of 156 male Wistar rats were assigned into 4 groups(39 each according to the microwave dosage they received(0,2.5,5 and 10 mW/cm2.Irradiation was given 5 times/week and 6 minutes for each exposure for one month.Five rats of each group were sacrificed at each time point(6h and day 7,14,30 and 60 after irradiation,the structural changes in hippocampus tissues BBB were observed by light and electron microscopy.Another 3 rats of each group were sacrificed after an intravenous injection of 2% Evans blue(EB at the time points of 6h and day 7 and 30 after irradiation,and the change in BBB permeability was examined by laser scanning confocal microscopy.Western blotting,real-time PCR and image analysis were used to detect the gene and protein expression of occludin in hippocampus of rats.Results After microwave irradiation in doses of 2.5,5 and 10 mW/cm2,respectively,on day 7,14 and 30,the astrocytes were found to be swollen,the capillary gaps of hippocampus were broadened and tight junction(TJ structure was inconspicuous or widened.In sham-group(0 mW/cm2,the red fluorescence of EB was limited in lumens of blood vessels,while in 5 and 10 mW/cm2 groups,Evans blue was dispersed surrounding the blood vessels at 6h and day 7 till day 30 in an irradiation dose-dependent manner.In 5 and 10 mW/cm2 groups,the expression of occludin protein in hippocampus decreased at day 14(P 0.05.In the 2.5,5 and 10 mW/cm2 groups,mRNA expression of occludin began to significantly decrease at day 7 and 14 and it lowered to the nadir at day 30(P 0.05.Conclusions A long-term microwave irradiation with dosage of 2.5 to 10 mW/cm2 may destroy the structure of BBB of rats’ hippocampus and increase permeability in a radiation

  8. Detecting Radiation-Induced Injury Using Rapid 3D Variogram Analysis of CT Images of Rat Lungs

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. A systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury. Results of the International Collaboration on MTBI Prognosis (ICoMP)

    DEFF Research Database (Denmark)

    Godbolt, Allison; Cancelliere, Carol; Hincapié, Cesar A

    2014-01-01

    -defined criteria. Peer-reviewed reports in six languages were considered. Study selection: Systematic reviews, meta-analyses, randomized controlled trials (RCTs), cohorts and case-control studies, with a minimum of 30 MTBI cases in subjects of any age, assessing the risk of dementia or CCI after MTBI were selected...... synthesis: Evidence from accepted studies was synthesized qualitatively according to modified SIGN criteria and prognostic information was prioritized as exploratory or confirmatory, according to design. Of 77 914 records screened, 304 articles were eligible and reviewed. Methodological quality......Objective: To synthesize the best available evidence regarding the risk of dementia and chronic cognitive impairment (CCI), following mild traumatic brain injury (MTBI). Data sources: MEDLINE and other databases were searched (2001–2012), using a previously published search strategy and pre...

  10. Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Songhua Xiao; Chaohui Duan; Qingyu Shen; Yigang Xing; Ying Peng; Enxiang Tao; Jun Liu

    2009-01-01

    BACKGROUND:Previous studies have shown that transplantation of vascular endothelial growth factor (VEGF)-modified neural stem cells (NSC) provides better outcomes,compared with neural stem cells,in the treatment of brain damage.OBJECTIVE:To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury,and to determine neuron-specific enolase (NSE) expression in the brain.DESIGN,TIME,AND SETTING:The randomized,controlled study was performed at the Linbaixin Experimental Center,Second Affiliated Hospital,Sun Yat-sen University,China from November 2007 to October 2008.MATERIALS:VEGF-medified C17.2 NSCs were supplied by Harvard Medical School,USA.Streptavidin-biotin-peroxidase-complex kit (Boster,China) and 5,6-carboxyfluorescein diacetate succinimidyl ester (Fluka,USA) were used in this study.METHODS:A total of 84 Sprague Dawley rats were randomly assigned to a blank control group (n=20),model group (n=20),NSC group (n=20),and a VEGF-modified NSC group (n=24).Rat models of radiation-induced brain injury were established in the model,NSC,and VEGF-modified NSC groups.At 1 week following model induction,10 μL (5×10~4 cells/μL) VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups.A total of 10 μL saline was injected into rats from the blank control and model groups.MAIN OUTCOME MEASURES:NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation.RESULTS:NSE expression was significantly decreased in the brains of radiation-induced brain injury rats (P<0.05).The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups,compared with the model group (P<0.05).NSE expression significantly increased in the VEGF-modified NSC group,compared with the NSC group,at 6 weeks following transplantation (P<0.05).CONCLUSION:VEGF-modified NSC

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

    Science.gov (United States)

    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 irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p 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. PAX2与急慢性肾脏疾病研究进展%The role of PAX2 in acute kidney injury and chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    王秀丽; 赵成广(综述); 吴玉斌(审校)

    2016-01-01

    Paired box2 ( PAX2 ) is a transciption factor which mainly expressed in the developing kid-ney. Researches indicate that PAX2 promote the transcription through interactions with the adaptor PAX transac-tivation domain interacting protein(PTIP). Otherwise,PAX2 protein can lead to chromatin compaction and gene silencing through interactions with Grg4. PAX2 reexpressed in acute kidney injury and involved in promoting cell proliferation. Congenital PAX2 gene mutation is closely related to congenital abnormalies of the kidney and uri-nary tract. In chronic kidney disease,PAX2 promote proliferation and cyst formation. Here,the recent researches on the function of PAX2 and its role in acute kidney injury and chronic kidney disease are reviewed.%配对盒基因2(paired box2,PAX2)是一种核转录因子,表达在发育期肾脏。研究表明PAX2通过与PTIP的相互作用使染色质处于可转录状态,与Grg4的相互作用削弱了其与PTIP结合而抑制转录。 PAX2在急性肾损伤时再表达,参与促进细胞增殖修复。先天PAX2基因突变与先天性肾脏输尿管异常密切相关。在慢性肾脏疾病,PAX2起到促进增殖及囊肿形成的作用。该文就PAX2的功能及其在急性肾损伤和慢性肾脏疾病中作用的相关研究进行综述。

  13. Detecting malingering in traumatic brain injury and chronic pain with an abbreviated version of the Meyers Index for the MMPI-2.

    Science.gov (United States)

    Aguerrevere, Luis E; Greve, Kevin W; Bianchini, Kevin J; Meyers, John E

    2008-01-01

    Meyers, Millis, and Volkert [Meyers, J. E., Millis, S. R., & Volkert, K. (2002). A validity index for the MMPI-2. Archives of Clinical Neuropsychology, 17, 157-169] developed a method to detect malingering in chronic pain patients using seven scales from the Minnesota Multiphasic Inventory-2 (MMPI-2). This method may be impractical because two of the scales (Obvious minus Subtle and Dissimulation-revised) are not reported by the commercially available Pearson computerized scoring system. The current study recalculated the Meyers Index using the five Pearson-provided scales in the chronic pain data sets of Meyers et al. [Meyers, J. E., Millis, S. R., & Volkert, K. (2002). A validity index for the MMPI-2. Archives of Clinical Neuropsychology, 17, 157-169] and Bianchini, Etherton, Greve, Heinly, and Meyers [Bianchini, K. J., Etherton, J. L., Greve, K. W., Heinly, M. T., & Meyers, J. E. (in press). Classification accuracy of MMPI-2 validity scales in the detection of pain-related malingering: A known-groups approach. Assessment], and the traumatic brain injury data of Greve, Bianchini, Love, Brennan, and Heinly [Greve, K. W., Bianchini, K. J., Love, J. M., Brennan, A., & Heinly, M. T. (2006). Sensitivity and specificity of MMPI-2 validity scales and indicators to malingered neurocognitive dysfunction in traumatic brain injury. The Clinical Neuropsychologist, 20, 491-512]. Classification accuracy of the abbreviated Meyers Index was comparable to the original. These findings demonstrate that the abbreviated Meyers Index can be used as a substitute of the original Meyers Index without decrements in classification accuracy.

  14. The Zarit Caregiver Burden Interview Short Form (ZBI-12 in spouses of Veterans with Chronic Spinal Cord Injury, Validity and Reliability of the Persian Version

    Directory of Open Access Journals (Sweden)

    Mohammad T. Rajabi Mashhadi

    2015-01-01

    Full Text Available Background:  To test the psychometric properties of the Persian version of Zarit Burden Interview (ZBI-12 in the Iranian opulation.  Methods: After translating and cultural adaptation of the questionnaire into Persian, 100 caregiver spouses of Iran-Iraq war (1980-88 veterans with chronic spinal cord injury who live in the city of Mashhad, Iran, invited to participate in the study. The Persian version of ZBI-12 accompanied with the Persian SF-36 was completed by the caregivers to test validity of the Persian ZBI-12.A Pearson`s correlation coefficient was calculated for validity testing.In order to assess reliability of the Persian ZBI-12, we administered the ZBI-12 randomly in 48 caregiver spouses again 3 days later. Results:  Generally, the internal consistency of the questionnaire was found to be strong (Cronbach’s alpha 0.77. Intercorrelationmatrix between the different domains of ZBI-12 at test-retest was 0.78. The results revealed that majority of questions the Persian ZBI_12 have a significant correlation to each other. In terms of validity, our results showed that there is significant correlations between some domains of the Persian version the Short Form Health Survey -36 with the Persian Zarit Burden Interview such as Q1 with Role Physical (P=0.03,General Health (P=0.034,Social Functional (0.037, Mental Health (0.023 and Q3 with Physical Function (P=0.001,Viltality (0.002, Socil Function (0.001.  Conclusions:  Our findings suggest that the Zarit Burden Interview Persian version is both a valid and reliable instrument for measuring the burden of caregivers of individuals with chronic spinal cord injury.

  15. Prokineticin 2 Upregulation in the Peripheral Nervous System Has a Major Role in Triggering and Maintaining Neuropathic Pain in the Chronic Constriction Injury Model

    Directory of Open Access Journals (Sweden)

    Roberta Lattanzi

    2015-01-01

    Full Text Available The new chemokine Prokineticin 2 (PROK2 and its receptors (PKR1 and PKR2 have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7 reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi and in the ipsilateral DRG since 6 dpi. PROK2 protein overexpression was evident in Schwann Cells, infiltrating macrophages and axons in the peripheral nerve and in the neuronal bodies and some satellite cells in the DRG. Therapeutic treatment of neuropathic mice with the PKR-antagonist, PC1, impaired the PROK2 upregulation and signalling. This fact, besides alleviating pain, brought down the burden of proinflammatory cytokines in the damaged nerve and prompted an anti-inflammatory repair program. Such a treatment also reduced intraneural oedema and axon degeneration as demonstrated by the physiological skin innervation and thickness conserved in CCI-PC1 mice. These findings suggest that PROK2 plays a crucial role in neuropathic pain and might represent a novel target of treatment for this disease.

  16. Prokineticin 2 Upregulation in the Peripheral Nervous System Has a Major Role in Triggering and Maintaining Neuropathic Pain in the Chronic Constriction Injury Model

    Science.gov (United States)

    Lattanzi, Roberta; Maftei, Daniela; Marconi, Veronica; Florenzano, Fulvio; Franchi, Silvia; Borsani, Elisa; Rodella, Luigi Fabrizio; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

    2015-01-01

    The new chemokine Prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI) of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7) reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi) and in the ipsilateral DRG since 6 dpi. PROK2 protein overexpression was evident in Schwann Cells, infiltrating macrophages and axons in the peripheral nerve and in the neuronal bodies and some satellite cells in the DRG. Therapeutic treatment of neuropathic mice with the PKR-antagonist, PC1, impaired the PROK2 upregulation and signalling. This fact, besides alleviating pain, brought down the burden of proinflammatory cytokines in the damaged nerve and prompted an anti-inflammatory repair program. Such a treatment also reduced intraneural oedema and axon degeneration as demonstrated by the physiological skin innervation and thickness conserved in CCI-PC1 mice. These findings suggest that PROK2 plays a crucial role in neuropathic pain and might represent a novel target of treatment for this disease. PMID:25685780

  17. Effect of a chronic and moderate ozone pollution on the phenolic pattern of bean leaves (Phaseolus vulgaris L. cv Nerina): relations with visible injury and biomass production.

    Science.gov (United States)

    Kanoun, M; Goulas, M J.P.; Biolley, J -P.

    2001-05-01

    From sowing, bean (Phaseolus vulgaris L. cv Nerina) plants were exposed to three chronic doses of ozone for 7h.day(-1): non-filtered air (NF), non-filtered air supplied with 40nl.l(-1) ozone (NF+40) and non-filtered air supplied with 60nll(-1) ozone (NF+60). Four harvests were carried out 6, 13, 20 and 27 days after emergence. Either primary leaves, or first trifoliate leaves, or both were sampled as far as possible. For each sampled leaf, visible ozone injuries were registered, the free polyphenolic pool was analysed using HPLC and the dry matter was weighed. Visible damage on leaves was related to both exposure time and ozone concentration added. There were no adverse effects of added ozone on the biomass of primary leaves while a significant reduction of first trifoliates dry matter could be observed (NF+60 atmosphere, third and fourth harvest). Among the normally occurring phenolics, we detected a significant decrease in the accumulation of a hydroxycinnamic acid derivative as the ozone concentration increased. Nevertheless, we demonstrated that this ozone-induced modification could be sometimes distinguishable with difficulties from changes expected to be of development relevance. Beside this phenolic disbalance, we detected a de novo biosynthesis of compounds that closely depended on the level of visible ozone injury. Since their accumulation increased with leaf damage, these ozone-induced phenolics could be used to detect phytotoxic ambient levels of tropospheric ozone.

  18. Examining the Effectiveness of Mindfulness Meditation for Chronic Pain Management in Combat Veterans with Traumatic Brain Injury

    Science.gov (United States)

    2013-01-01

    that carry nociceptive information about potential tissue damage to the brain, pain is the subjective perception that results from interpreting this... nociception , pain , distress, and disability may be perpetuated. Although sensory mechanisms of pain have been historically given the most attention...accompanying nociception (Solberg, 2009). Prolonged mindful observation and awareness of chronic pain sensations could lead to desensitization, leading to

  19. Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.

    Science.gov (United States)

    Bombas, A; Stein-Oakley, A N; Baxter, K; Thomson, N M; Jablonski, P

    1999-01-01

    Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.

  20. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay.

    Science.gov (United States)

    Kumar, P R Vivek; Seshadri, M; Jaikrishan, G; Das, Birajalaxmi

    2015-05-01

    This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year(-1)), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N=43, range 1.07 mSv year(-1) to 5.55 mSv year(-1)) and 9.62 mSv (N = 34, range 6.07 mSv year(-1) to 17.41 mSv year(-1)), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P=0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from our study suggest in vivo chronic low-level natural radiation provides an initial exposure that allows an adaptation to a subsequent higher radiation exposure, perhaps through improving DNA repair via an unknown mechanism. Therefore, further investigations would be necessary in this population to understand the biological and health effects of chronic low-level natural radiation exposures.

  1. Delta-tocotrienol suppresses radiation-induced microRNA-30 and protects mice and human CD34+ cells from radiation injury.

    Directory of Open Access Journals (Sweden)

    Xiang Hong Li

    Full Text Available We reported that microRNA-30c (miR-30c plays a key role in radiation-induced human cell damage through an apoptotic pathway. Herein we further evaluated radiation-induced miR-30 expression and mechanisms of delta-tocotrienol (DT3, a radiation countermeasure candidate, for regulating miR-30 in a mouse model and human hematopoietic CD34+ cells. CD2F1 mice were exposed to 0 (control or 7-12.5 Gy total-body gamma-radiation, and CD34+ cells were irradiated with 0, 2 or 4 Gy of radiation. Single doses of DT3 (75 mg/kg, subcutaneous injection for mice or 2 μM for CD34+ cell culture were administrated 24 h before irradiation and animal survival was monitored for 30 days. Mouse bone marrow (BM, jejunum, kidney, liver and serum as well as CD34+ cells were collected at 1, 4, 8, 24, 48 or 72 h after irradiation to determine apoptotic markers, pro-inflammatory cyto